Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic agent that causes severe pulmonary infection in immunocompromised individuals.
The incidence of PCP varies from 0.6 to 14 % in kidney transplant patients without prophylaxis and mortality reaches 50%.
Aim of study
To evaluate the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Patients and methods
Retrospective observational study studied 1502 adult kidney transplant recipients from Seoul National University Hospital in the period between 2000 to 2017 and compared the graft and survival outcomes between PCP positive and PCP negative groups
Results
A total of 68(4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for CMV and lack of initial antibiotic prophylaxis were risk factors for post transplant PCP
The PCP positive group had higher hazard ratios of graft failure and mortality than the PCP negative group
PCP event was not related to development of denovo DSA or pathological findings as T cell mediated rejection and interstitial fibrosis and tubular atrophy
Conclusion
PCP is a risk factor for long-term graft failure and mortality irrespective of rejection
Aretrospective study analyzed 1502 adult patients who had kidney transplantation at Seoul National University Hospital between 2000 and 2017.
Results:68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
Conclusions:PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
This is a retrospective observational study involved 1502 kidney recipients. The graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
68 patients developed PCP after transplantation. positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were the risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group. Limitations of the study are:
1- This was a retrospective study
2- antibiotics were given for 1 month
level of evidence 3
Background:
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients. While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome.
Method:
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
Results:
A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy. Conclusion:
PCP is a risk factor of long-term graft failure and mortality.
Is large study with relatively long period of follow up, however it is retrospective, single center study in restricted ethnic group.
This is a retrospective analysis of level 3 evidence
This was a retrospective observational analysis of the effect of PCP infection on long term graft survival in kidney transplant recipients.
1502 patients were followed for median of 6.2 years. out of which 68 (4.5%) patients developed PCP.
Risk factors for PCP includes: CMV and non use of antibiotic prophylaxis .
Population: 1502 adult patient post kidney transplantation, single centre, between 2000-2017
Intervention: Nil (Retrospective observational study)
Comparator: PCP negative vs PCP positive
Outcome:
Primary: graft survival and all-cause mortality (patient survival)
Secondary: TCMR, ABMR, IFTA and deNovo DSA
This paper demonstrated that PCP is associated with poor graft and patient survival. However the PCP event was not associated with subsequent, TCMR, ABMR or IFTA
What is the level of evidence provided by this article?
Level III
who get kidney transplants, who test positive for CMV, and who do not take oral prophylactic antibiotics are at increased risk of developing PCP. PCP greatly raises the risks of graft failure and mortality. In light of this, strong prophylaxis may be required to stop PCP and eventual transplant failure. Future clinical trials on the use of prophylaxis in kidney transplant patients will be built on the outcomes of the current study.
This article discusses the impact of Pneumocystis jirovecii pneumonia (PCP) on kidney transplant outcomes. PCP is an opportunistic infection that affects immunocompromised individuals, such as kidney transplant recipients. The study included 1,502 patients who underwent kidney transplantation between 2000 and 2017. The researchers found that PCP occurred in 4.5% of the patients, with a median time of 5.2 months after transplantation. CMV positivity and the non-use of oral prophylactic antibiotics were identified as risk factors for PCP. The occurrence of PCP was associated with an increased risk of death-censored graft failure, indicating that PCP infection contributes to long-term graft failure. However, this relationship was not dependent on rejection or other immunological factors. The study also found that PCP was associated with higher overall mortality in kidney transplant recipients. The findings highlight the importance of intensive treatment and prophylaxis for PCP after kidney transplantation to improve graft outcomes and patient survival. Further research is needed to determine the appropriate duration and dosage of PCP prophylaxis. level of evidence 3
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Its retrospective observational study published in BMC Nephrology 2019 Level 3 Evaluating the effect of PCP infection on kidney transplant outcomes including graft failure and rejection. Introduction: Infection is the second most common cause of death in patients post-kidney transplant after cardiovascular. PCP is a yeast-like fungus organism that can cause severe pulmonary infection in 0.6 to 14% of immunocompromised Patients and finally can cause death in up to 50%. Method: 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017 were included then divided according to PCP to PCP-negative and PCP-positive matched groups then graft and patient survival outcomes were compared between both groups Results: 1. 68 (4.5%) experienced PCP post-KT. The median time of PCP was 5.2 months and 79.4% of cases developed during the first year. CMV positivity and the non-use of PCP prophylactic drugs were associated with an increased risk of PCP. Death-censored graft failure was 13.2% of PCP-positive recipients 2. 88.9% of PCP-positive patients experienced acute kidney injury and 50% did not recover after recovery from PCP. 3. The PCP-positive group had higher hazard ratios of graft failure than the PCP-negative group. Limitation of the study: Retrospective study with limited data and no clear histopathological diagnosis of the cause of AKI associated with PCP. Conclusion: · Positivity for CMV, and non-use of oral prophylactic antibiotics is associated with increased risk of PCP. · PCP is associated with higher risks of graft failure and death. What is the level of evidence provided by this article? Level (3)
Introduction:
Pneumocystis jirovecii is a pathogen that causes severe lung infection in individuals with compromised immune systems. Pneumocystis jirovecii pneumonia (PCP) is a significant concern in kidney transplant recipients, with mortality rates of up to 50% despite antibiotic treatment. However, the impact of PCP on graft rejection and overall transplant outcomes has not been extensively studied. This article aims to analyze the effects of PCP on kidney transplant recipients.
Methods:
This retrospective observational study analyzed data from 1,502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. The collected data included demographic information, pre-transplant status, immunosuppressive therapy, PCP diagnosis, and cytomegalovirus (CMV) positivity. Graft and survival outcomes were compared between PCP-negative and PCP-positive groups. The primary outcome was death-censored graft failure, and the secondary outcome was all-cause mortality. Biopsy results for acute T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), interstitial fibrosis and tubular atrophy (IFTA), and donor-specific antibodies (DSAs) were also recorded.
Results:
All the recipients were male and had no history of prophylaxis. The results showed that CMV positivity and lack of prophylaxis were associated with a higher risk of PCP infection. Approximately 14% of PCP-positive patients experienced graft failure, and there was higher mortality at a median follow-up of 6.2 years, with an infection rate of 6.8 cases per 1000 person-years.
Discussion and Conclusion:
The study found that male gender and CMV positivity were associated with a higher risk of developing PCP, while the oral use of antibiotics was associated with a decreased risk. PCP infection was found to increase the risk of mortality and biopsy-proven graft loss due to AMR, TCMR, and IFTA. Therefore, prophylaxis is recommended to prevent PCP and reduce the risk of graft failure.
Level of Evidence:
This article provides Level III evidence.
Backgrounds: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in kidney transplant recipients. While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome.
Method: This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
Results: A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusions: PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
Summary of article-This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Graft and survival outcomes were compared between PCP-negative and PCP-positive groups.The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality.
Results-Of the 1502 patients,68(4.5%) experienced PCP after kidney transplantation.79.4 % of cases developed during the first year after transplantation .Among 68 PCP positive receipt ,9 (13.2%) developed graft failure.Although all variable were adjusted, in this study ,PCP positive recipient had a higher risk of death censored Graft failure ,than PCP Negative recipient .All cause mortality was higher in PCP positive group than PCP negative group.
The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP. The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs. Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients.
Discussion
The given article is based on a retrospective observational study which analyzed kidney transplant recipients in Seoul between the years of 2000 and 2017.
Out of the total participants of the base study, 68 developed PCP post transplant. Risk factors were found to be CMV positivity and lack of initial antibiotic prophylaxis. About the causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in immunocompromised people. It can affect kidney transplant recipients who do not have prophylaxis and can cause fatalities in upto 50% of those affected even with aggressive antibiotic cover.
This fungi cannot be consistently cultured, and thus its life cycle is not known.
One of the major risk factors includes CMV infection. This is because CMV can modify host immune response, thus leading to suppression of the immune system. The pathogen accelerates aging of host T cells, thus increasing vulnerability to PCP and decreasing rate of infection resolution. This is also why co-infection can worsen pulmonary impairment.
Antibiotic cover and pre transplant dialysis are protective factors against PCP. Pre transplant resolution of uremia lowers the risk of PCP in the post transplant period.
Adequate prophylaxis needs to be for a period of 3-6 months post transplantation.
Conclusion
PCP can have significant negative effects on both the kidney graft and life of the patient. Risk factors include male gender, CMV infection and no antibiotic prophylaxis. Thus, adequate prophylaxis and early intervention and appropriate treatment are crucial to achieving good outcome.
Level of evidence:
This is a retrospective observational study, and thus the level of evidence is 3.
1. Please summarise this article. Introduction Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immune-compromised hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy. PCP is an important cause of morbidity and mortality in kidney transplant recipients and important cause of long-term graft failure. The effect of PCP on graft rejection and overall graft outcomes has been less explored. This article analysed impacts of pneumocystis jirovecii pneumonia kidney transplant. Methods
– Retrospective observational study analysed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
– Data collected: demographics, pretransplant status (cause of ESRD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy, PCP diagnosis (based on CXR and PCR or direct IF staining), CMV positivity.
– Graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
– Primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
– Secondary outcome was all-cause mortality
– Biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded.
– Protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
– Indication biopsies were also done, when suspected rejection or graft dysfunction, Results The primary outcomes were death censored graft failure, secondary outcomes were all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). Protocol biopsy were performed “0” hour, post-transplantation day-10, at one year, yearly thereafter. All the recipient were male, with no history of prophylaxes. The result showed that CMV positivity and lack of use of prophylaxes was associated more with PCP infection. Around 14% of PCP positive patients had graft failure, higher mortality at a median follow-up of 6.2years (infection rate 6.8 cases per 1000 per person-years). Discussion and conclusion; The study found male gender, CMV positivity were at higher risk of developing PCP, while oral use of antibiotic was associated with decreased risk of PCP. PCP infection has increased risk of mortality and biopsy proven graft loss with AMR, T-cell mediated rejection and IFTA. So prophylaxes is recommended to prevent PCP and risk graft failure.
2. What is the level of evidence provided by this article? Level III
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts. And the aim of this study is to evaluate the impact of Pneumocystis jirovecii on long-term graft outcome.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
The main results of the study were:
– male gender and CMV positivity were risk factors associated with PCP;
– the use of oral prophylactic antibiotics seemed to prevent the risk of PCP;
– PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
– the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipien
– Pre-transplant dialysis was newly identified as a protective factor of PCP.
Thus, a more vigorous prophylaxis can bring better results.
2,What is the level of evidence provided by this article?
This is a retrospective study, lika a case control – level 03.
Introduction This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients and important cause of long term graft failure and mortality.
Methods
– Retrospective observational study
–Analysed 1502 adult patients transplanted between 2000 and 2017
–Data collected included demographics, pretransplant status (cause of ESKD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy exposure, PCP diagnosis (based on CXR and PCR or direct immunofluorescence staining), CMV positivity
–Primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
–Secondary outcome was all-cause mortality
–Data on biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded
–Protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
–Indication biopsies were also done.
Results The primary outcomes was death censored graft failure, secondary outcomes was all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). These protocol biopsy were performed zero time post-transplantation, on the day, and one year, there after every year. All the recipient were male, with no history of prophylaxes. The result showed that CMV positivety and lack of use of prophylaxes was more associated with PCP infection. Around 14% of PCP positive patients had graft failure, and higher mortality. The median duration of follow-up was 6.2years and they found an infected rate of 6.8 cases per 1000 per person-years.
Conclusion PCP has long been a risk factor. -Term transplant rejection and mortality with or without rejection. Therefore, proper prevention and treatment are necessary to avoid the side effects of PCP transplantation.
What is the level of evidence provided by this article?
The article deals with how pneumocystis jirovecii pneumonia is affecting kidney transplant. PCP is an important underlying cause of morbidity and mortality in recipient of kidney transplant. Discussion
The article relies on a retrospective observational study which analyzed kidney transplant recipients in Seoul between 2000 & 2017.
From total participants , 68 developed PCP following transplant. Risk factors included CMV positivity and lack of initial prophylaxis. The causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in vulnerable immunocompromised patients. It can affect kidney transplant recipients without prophylaxis and can lead to mortalities in up to 50% of those affected even with aggressive antibiotic treatment.
This organism cannot be cultured, so its life cycle is not known.
An important risk factors is CMV infection; as CMV can manipulate host immune response, resulting in suppression of the immune system. The pathogen enhances aging of host T cells, resulting in increased possibility of PCP and decreasing rate of infection recovery. Co-infection can worsen pulmonary affection..
Antibiotic therapy and prior transplant dialysis are protective against PCP. Pre transplant amelioration of uremia decreases the risk of PCP following transplantation.
Adequate prophylaxis should be for 3-6 months following transplantation. Conclusion
PCP has considerable negative impact on both kidney graft and patient survival. Risk factors include male gender, infection with CMV and no measure of antibiotic prophylaxis. So, good prophylaxis and early management with proper treatment are essential for better outcomes.
Level of evidence:
level of evidence is 3;retrospective observational study.
. Summary; PCP remains an important cause of morbidity and mortality in kidney transplant recipient. This is infection of immunocompromissed patients, with development of strong immunosuppression these patients are prone to develop opportunistic infections. According to literature the infections are second most factor in mortality and morbidity of these patients. The incidence of PCP varies but it’s around 0.6 to 14% among kidney transplant patients without prophylaxes and with a mortality of 50%. Methods; This was a retrospective observational study done at Seoul National hospital in 2017, number of patients were 2000, of them have received dual kidney-pancreas and kidney-liver transplantation. Data collection; Data collected from kidney recipient were collected from the electronic medical records. Demographic characteristic were age, height, weight, gender, BMI were taken. Other duration of transplantation, cause of renal failure, and other co-morbidities were collected. Results PCP and transplant outcomes; The primary outcomes was death censored graft failure, secondary outcomes was all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). These protocol biopsy were performed zero time post-transplantation, on the day, and one year, there after every year. All the recipient were male, with no history of prophylaxes. The result showed that CMV positivety and lack of use of prophylaxes was more associated with PCP infection. Around 14% of PCP positive patients had graft failure, and higher mortality. The median duration of follow-up was 6.2years and they found an infected rate of 6.8 cases per 1000 per person-years. Discussion and conclusion; The study found male gender, CMV positivity were at higher risk of developing PCP, while oral use of antibiotic was associated with decreased risk of PCP. PCP infection has increased risk of mortality and biopsy proven graft loss with AMR, T-cell mediated rejection and IFTA. So prophylaxes is recommended to prevent PCP and risk graft failure. Level of study III
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts
Methods Study design and subjects
The study design was approved by the institutional review board of Seoul National University Hospital (no. H1805-173-948) and complied with the Declaration of Helsinki. This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records. Demographic characteristics including age, gender, height, weight, and body mass index were collected. Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes, was evaluated.
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018. Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected. Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter. Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
Baseline characteristics and risk factor of PCP
The median duration of follow-up was 6.2 years (interquartile range, 3.0–9.6 years; maximum 18.3 years). Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months (interquartile range, 3.9– 10.0 months), and 79.4% of cases developed during the first year after transplantation. There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
PCP and transplant outcomes
We performed propensity score matching to mitigate the difference in baseline characteristics between the PCP-positive and -negative groups. All the patients were male and had no history of prophylactic antibiotics usage after transplantation. During the admission period, 8 of 9 patients (88.9%) experienced acute kidney injury according to the Kidney Disease Improving Global Outcomes criteria and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP. To determine the cause of the elevated risk of graft failure, we evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs. However, these outcomes did not differ between PCP-positive and –negative groups.
During the follow-up period, 11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and -negative groups, respectively. The 28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%). All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
Discussion
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured
Due to little knowledge about Pneumocystis jirovecii, it is necessary to investigate whether the long term effect of PCP on allografts is due to the infection alone or with chronic inflammatory process and other unknown mechanisms.
Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. Nevertheless, occurrence of PCP was significantly associated with overall graft failure. As has been previously demonstrated, viral infections such as CMV, BK virus, and hepatitis C virus, and certain bacterial infections such as Pseudomonas aeruginosa, affect allograft dysfunction by modulating non-immunological factors such as hemodynamic change in addition to immunological factors
there are some limitations. First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively. Nevertheless, the study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes. Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects. The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes. However, this did not hinder the study purpose on the relationship between PCP and transplant outcomes.
Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure. The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
PCP is an oppurtunistic fungi that is present in the post transplant patient…the incidence is somewhere between 0-14%… Infection is the second commonest cause of death with the functioning graft after cardiovascular diseases after transplant… The Association between CMV and BKV for graft rejection is established due to the immunomodulation effect of the viruses…The observational retrospective study conducted in university of Seoul….The study included 1827 kidney transplant patient between Jan 2000 to Dec 2017..They evaluated for graft and survival outcome between those who had PCP and those without PCP infection….
Exclusion criteria were patients less than 18 years old and those with simultaneous kidney pancreas transplant or kidney liver transplants…After the exclusion remaining 1502 patients were finally included for ananlysis .. PCP was defined as clinical suspisicon + PCR for PCP positivity or IF stain on BAL or sputum…Initial use of prophylactic antibiotic was defined was prescription of TMP-SMX for 4 weeks atleast…. CMV positivity was also defined in the study as more than 20 copies/ml on PCR….
Primary outcome of the study was return to dialysis or transplantation….The secondary outcome of the study was all cause mortality….. There was a protocol biopsy done at the time of the transplant on day 0 and 1 year post transplantation and alternate year thereafter…
The median follow up was 6.2 years with 4.5% of the patients having PCP post transplant…. The average time to develop PCP in this study was 5.2 months….
The results showed that male gender and CMV positivity and lack of use of prophylaxsis was associated with more PCP…..
Around 14% of the PCP positive patients had graft failure….. The graft failure episodes were attributed to concurrent AKI factors and not related to immunological factors
They also found that PCP positive cohort had overall higher mortality…
Limitation of the study are it is a retrospective study and the cause effect relationship between PCP and mortality cannot be established…. The study also used oral antibiotics for 1 month duration only as compared to 3-6 months recommended by KDIGO
This is a retrospective observational study which was approved by the institutional review board of Seoul National University Hospital. This study included 1827 kidney transplanted patients at Seoul National University Hospital from January 2000 to December 2017 evaluated for graft and survival outcome between those who have Pneumocystis jiroveci pneumonia infection and those have no Pneumocystis jiroveci pneumonia infection.. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded. Consequently, the remaining 1502 patients were finally included and their data were reviewed.
They found that male gender and CMV positivity were risk factors associated with PCP infection and prevented by oral prophylactic antibiotics.
PCP infection was associated with both graft failure and overall mortality.
recommendations for intensive tratment and prophylaxis.
Introduction :Infection is an important factor in relation to the risk
of death in kidney transplant recipients, and the second
most common cause of death after cardiovascular dis-
ease in patients with functioning grafts.Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocom-
promized hosts.The incidence of P. jirovecii pneu-
monia (PCP) varies from 0.6 to 14% among kidney
transplant recipients without prophylaxis, with a mortal-
ity of up to 50% despite aggressive antibiotic therapy.
In this study, evaluation of the impact of PCP on
kidney transplant outcomes, including graft failure and
rejection done.
Method :This retrospective observational study included
total 1827 patients who had kidney transplantation at
Seoul National University Hospital from January 2000 to
December 2017.The primary outcome was death-censored graft failure
defined as a return to dialysis or kidney re-
transplantation. The secondary outcome was all-cause mortality.
Result :Among 68 PCP-positive
recipients, 9 (13.2%) patieIntroduction :Infection is an important factor in relation to the risknts developed death-censored
graft failure.During the follow-up period, 11 patients (16.2%) and
13 patients (11.0%) died in the PCP-positive and
-negative groups, respectively. The 28 PCP-positive pa-
tients had concurrent other infectious diseases, and 8
patients died (28.6%). All-cause mortality was higher in
the PCP-positive group than in the PCP-negative group.
Conclusion :All-cause mortality was higher in
the PCP-positive group than in the PCP-negative group.It is related to increased,morbidity,mortality in transplant patient.
Level of Evidence :This is a retrospective observational study, and thus the level of evidence is 3
This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients.
Discussion
The given article is based on a retrospective observational study which analyzed kidney transplant recipients in Seoul between the years of 2000 and 2017.
Out of the total participants of the base study, 68 developed PCP post transplant. Risk factors were found to be CMV positivity and lack of initial antibiotic prophylaxis.
About the causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in immunocompromised people. It can affect kidney transplant recipients who do not have prophylaxis and can cause fatalities in upto 50% of those affected even with aggressive antibiotic cover.
This fungi cannot be consistently cultured, and thus its life cycle is not known.
One of the major risk factors includes CMV infection. This is because CMV can modify host immune response, thus leading to suppression of the immune system. The pathogen accelerates aging of host T cells, thus increasing vulnerability to PCP and decreasing rate of infection resolution. This is also why co-infection can worsen pulmonary impairment.
Antibiotic cover and pre transplant dialysis are protective factors against PCP. Pre transplant resolution of uremia lowers the risk of PCP in the post transplant period.
Adequate prophylaxis needs to be for a period of 3-6 months post transplantation.
Conclusion
PCP can have significant negative effects on both the kidney graft and life of the patient. Risk factors include male gender, CMV infection and no antibiotic prophylaxis. Thus, adequate prophylaxis and early intervention and appropriate treatment are crucial to achieving good outcome.
Level of evidence
This is a retrospective observational study, and thus the level of evidence is 3.
EFFECT OF PJP ON KIDNEY TRANSPLANT
background-
cardiovascular and infection is most commom cause of death after transplant
PJP is seen in 0.6 to 14 % of transplant without prophylaxis and 50% mortality
BKV and CMV is associated with rejection and graft loss BUT little is known about PJP and rejection risk and graft function
study
retrospective
in korea
1827 kidney transplants
1502 included afted excluding less than 18 yrs , SPK liverand kidnet tx
diagnosis of PCP
. PCP was defined as the presence of findings suspicious of PCP
detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase
chain reaction or direct immunofluorescence stain of
sputum or bronchoalveolar lavage fluid
PCP
4 weeks after transplant with bactrim
outcome was eath censored graft failure
retransplant or return to dialysis
protocol biopsy as well as indication biopsy done
results
68(4/5%0 had PCP
80% IN FIRST year
median follow up 6.2 yrs
pcp and graft outcome
9 out of 68 had graft failure
significant relationship was found between graft failure and PCP positivity
all patients were MALE
NO PCP received
8 out of 9 has AKI
PCP do not increases the risk of rejection , IFTA , DSA
non immunological cause for graft loss associated with PCP
RISK FACTORS
make gender
CMV positivity
absence of PCP
PJP is associated with graft loss and death
pre transplant dialysis may protect againg PJP – furtehr study is required
PCP is MUST for 3-6 months after transplant
LIMITATION OF STUDY
retrospective
1 month of PCP given which is less than standard
Introduction
· With the improvement of immunosuppressive regimens, graft loss became less, but the mortality rates in patients with functioning grafts remain unchanged
· Infection is the second most common cause of death after cardiovascular disease in recipients with functioning grafts
· Pneumocystis jirovecii pneumonia is an opportunistic infection occurs in immunocompromized patients with an incidence of 0.6-14% among kidney transplant recipients without prophylaxis, and a mortality of up to 50% despite aggressive antibiotic therapy
· This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection. Methods
· Inclusion criteria: Total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017, with final number 1502 patients.
· Exclusion criteria: 1) Patients who were under 18 years old, 2) Patients who received simultaneous kidney–pancreas or kidney–liver transplants
· Data from the kidney transplant recipients were collected from the electronic medical records.
· PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest CT combined with + PCP or direct immunofluorescence stain of sputum or BAL fluid
· Prophylaxis with trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
· CMV infection considered + if PCR is > 20 copies/ml
Discussion
· This study found that male gender and CMV positivity were risk factors for PCP, and the use of oral prophylactic antibiotics may to prevent the risk of PCP
· PCP increased the risk of long-term graft failure; but this was not related to rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
· As PCP was associated with graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
· CMV infection was found to increases a risk of PCP
· Pre-transplant dialysis was newly identified as a protective factor of PCP as uremia alter the immunological responses
Limitations of the study
· It was a retrospective, making it difficult to demonstrate cause and effect definitively.
· The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
· The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes.
· The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion
· Male gender, positive CMV, and non-use of oral prophylactic antibiotics, are risk factors for PCP
· PCP increases the risks of mortality and graft failure
· Prophylaxis is recommended to prevent PCP and subsequent graft failure.
Among infections in kidney transplant recipients, PCP is an important cause of mortality & morbidity. Though certain infections like CMV, BK virus have an association with acute rejection & poor graft survival in early post transplant period, but there is little known in case of PCP infection. This retrospective observational study analyzed 1502 kidney transplant recipient patients at Seoul National University between 2000 and 2017. Total 68 patients developed PCP after transplantation & multivariable cox analysis showed CMV positivity & absence of antibiotic prophylaxis were the risk factors. The PCP positive group had a higher hazard ratio of graft failure compared to PCP negative group but PCP infection does not showed with subsequent development of DSA, rejection and IFTA.
I. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Summarise this article
Backgound
– Cardiovascular disease and infections are the leading causes of mortality among kidney transplant recipients.
– PCP is a significant cause of morbidity and mortality in kidney transplant recipients.
– Among kidney transplant recipients without prophylaxis, incidence of PCP varies from 0.6-1.4%.
– A 50% mortality is reported despite aggressive antibiotic therapy.
Methods
– Retrospective observational study
– analysed 1502 adult patients transplanted between 2000 and 2017
– data collected included demographics, pretransplant status (cause of ESKD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy exposure, PCP diagnosis (based on CXR and PCR or direct immunofluorescence staining), CMV positivity
– primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
– secondary outcome was all-cause mortality
– data on biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded
– protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
– indication biopsies were also done
Results
– out of the 1502 patients, 68 patients (4.5%) developed PCP post kidney transplantation
– median time to develop PCP was 5.2months and 79.4% of patients developed PCP during the 1st year following transplantation
– CMV positivity and lack of antibiotic prophylaxis were associated with an increased risk of PCP
– of the 68 PCP-positive patients, 9 developed death-censored graft failure
– the PCP-positive group was at increased risk of graft failure and mortality compared to the PCP-negative group
– PCP infection was not associated with subsequent development of de novo DSAs or pathologic features of TCMR, ABMR or IFTA on kidney biopsy suggesting that the graft failure rates were not attributable to the immunological transplant episodes
– in the follow up period, 11 patients (16.2%) died in the PCP-positive group compared to 13patients (11%) in the PCP-negative group
– the 28 PCP-positive recipients had concurrent infectious diseases and 8 patients (28.6%) died
– all-cause mortality was higher in the PCP-positive group compared to the PCP-negative group
– the commonest cause of death was ARDS related with PCP
Discussion
– much remains unknown regarding PCP i.e., the lifecycle, epidemiology, clinical implications, whether the long-term effects on the graft are due to the infection alone or due to chronic inflammation or other unknown mechanisms
– male sex and CMV positivity were associated with PCP
– use of antibiotic prophylaxis prevents the risk of PCP
– PCP increased the risk of long-term graft failure but this relationship was not dependent of rejection, IFTA or de novo DSAs
– intensive treatment and prophylaxis is recommended post-transplantation due to the increased risk of graft failure and mortality associated with PCP
– CMV infection modifies the host immune response hence it can increase the risk of PCP
– pretransplant dialysis has been identified as a protective factor of PCP – uremia alters immunological responses hence pretransplant resolution of uremia decreases the risk of post-transplant PCP
– occurrence of PCP does not affect the risk of developing acute rejection and production of de novo DSAs
– PCP was associated with overall graft failure
– viral infections (e..g., CMV, BKV, HCV) and some bacterial infections (e.g., pseudomonas aeruginosa) modulate non-immunological and immunological factors hence affecting graft dysfunction
– PCP did not increase risk of rejection meaning that nonimmunological factors may be the cause of these observations
– PCP infection can cause AKI and can also stimulate production of proinflammatory cytokines (e.g., IL-1, IL-6, IL-8) hence inducing graft injury
– mortality rate was high in PCP-positive patients
– 81.8% patients died within 3 months of PCP diagnosis, with the cause of death being PCP itself or other superimposed infections
– given these outcomes, PCP prophylaxis is strongly recommended
– KDIGO recommends PCP prophylaxis for 3-6months following transplantation
Study limitations
– retrospective study hence difficult to demonstrate cause and effect confidently
– observational study design hence cannot determine the mechanisms underlying the risk and the subsequent effect of PCP
– definition of antibiotic prophylaxis as 1 month – this is shorter than what is recommended in the guidelines i.e., 3-6 months
Conclusion
– male sex, CMV positivity and lack of antibiotic prophylaxis increase the risk of PCP
– PCP increases risk of graft failure and mortality
– antibiotic prophylaxis is needed to prevent PCP and subsequent graft failure
-Infection rank 2nd after cardiovascular dx as a cause of mortality post transplant. PCP incidence post transplant is 0.6-14% in KTR with no prophylaxis with mortality of upto 50%.The impact of PCP on graft dysfunction and mortality is well explored. This study looked into effects of PCP on KTR including graft dysfunction and rejection.
METHODS.
Study design and Subjects.
-Retrospective observational study on 1827 pts transplanted at Seoul National University Jan 2000 – Dec 2017.
-Exclusion -Pts < 18 yrs
-Those with simultaneous Pancreas and Kidney Transplant.
Data collection and definition.
-Data was electronically collected.
-PCP was defined as presence of suspicious finding of PCP by a radiologist + PCP PCR or IF stain on sputum or BAL.
-Initial use of prophylactic antibiotics was defined as prescription of septrin > 4 weeks one month post transplant.
-CMV positivity was taken as > 20 copies /ml on PCR or +VE results on viral cultures.
Transplant Outcomes.
-Primary outcomes; Return to dialysis or kidney transplantation.
-Secondary outcome – All cause mortality.
-Protocol biopsy done at zero time post perfusion on 0/7 and 1 yr post transplantation and alternate year thereafter.
Statistical analysis
-All analysis was done with stata software.
-Data expressed as mean +/- SD for continuous variables, Categorical variables on baselines xtics were done using x2 and fisher exact test with continuous variables analyzed with student T test.
-A P value of <0.05 was interpreted to be statistically significant.
RESULTS.
Baseline xtics and risk factors for PCP.
-Median follow up was 6.2 yrs with 4.5 % having PCP post transplant.
-Median time to develop PCP was 5.2 months.
-CMV positivity and no use of prophylactic antibiotics were associated with more PCP, equally more males had PCP than females.
PCP and transplant outcomes.
-13.2% of PCP +VE pts had graft failure.
-Graft failure amongst pts with PCP was possibly from non immunological factors like concurrent AKI and not typical immunological transplant episodes,
-PCP +VE group had a higher risk of mortality than PCP -VE cohort.
DISCUSSION.
-Male gender and CMV positivity are risk factors for PCP while prophylactic antibiotics seemed to be protective against PCP.
-Due to increased risk of graft dysfunction and mortality ,intensive treatment and prophylaxis recommended post transplant.
-In this study, pre transplant dialysis was found to reduce risk of PCP unlike other studies but this should not be done over a long duration pre transplant. Further studies are needed on pre transplant hemodialysis.
-As per KIDIGO ,PCP prophylaxis should be 3-6/12 post transplant. More studies needed on this.
LIMITATIONS.
-Retrospective study-Difficult to show cause and effects of PCP with certainty.
-Short duration of prophylactic antibiotics in study vs guidelines (1 vs 3-6/12).
-Pathophysiology behind effects of PCP not established.
CONCLUSION.
-Male gender, no prophylaxis and CMV positivity are risk factors to PCP post transplant. More studies needed in future to guide prophylaxis use post kidney transplant.
Summary: Introduction:
Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in kidney transplant recipients. The incidence ranges from 0.6-14% with a mortality rate up to 50%.
Methods:
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. This study included total 1827 patients who had kidney transplantation. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65), total 325 were excluded. PCP positive and PCP negative groups were studied, and graft outcomes and patient survival were compared between groups.
Results:A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusion:Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases Fig. 2 Patient survival curves in the PCP-positive and -negative patients. P value was obtained using the log-rank test. Dashed line, PCP-positive; solid line, PCP-negative Kim et al. BMC Nephrology (2019) 20:212 Page 6 of 8 both the risks of mortality and graft failure.
This retrospective observational study conducted by Kim and his colleagues at Seoul National university hospital looked at an important aspect of long term graft outcome in patients developing PJP during course of illness.
They analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
They found that total of 68 patients (4.5%) developed PCP after transplantation. The risk factors for developing PJP were CMV and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
This study confirms the fact that PJP prophylaxis is mandatory for all transplant patients and occurrence of PJP is associated with reduced long term graft survival and mortality.
Abstract: Backgrounds: Pneumocystis jirovecii pneumonia (PCP) IS important cause of morbidity and mortality in
kidney transplant recipients. Method: retrospective observational study Result: the positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis are risk factors of post-transplant PCP. The PCP-positive group had higher risk of graft failure and mortality than the PCP-negative group. the PCP infection is not related with subsequent development of de novo donor-specific antibodies or pathologic findings, of T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy. Conclusions: PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP. Background:
Infection is an important factor for death in kidney transplant recipients, and the second most common cause of death after CVD in patients with functioning grafts .
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts.
The incidence of P. (PCP) is 0.6 to 14% without prophylaxis, with a mortalityof 50% despite aggressive treatment . Certain infections like (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period . therefore appropriate infection prophylaxis and treatment regimens could be implemented to reduce immunological complications. Results:
The infection rate is 6.8 cases per 1000 person-years. The median time to the development
of PCP was 5.2 months , and 79.4% of cases developed during the first year after transplantation.
Ø CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP .
Ø the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients .
To determine the cause of graft failure, this study evaluated the effect of PCP on the rejection, interstitial fibrosis and tubularatrophy, and de novo DSAs. But these did not differ between PCP-positive and –negativegroups . These results suggest that different graft failure rates is not due the conventional immunological transplant episodes, but could be due to non-immunological factors such as concurrent acute kidney injury.
Ø All-cause mortality was higher in the PCP-positive than in the PCP-negative .
Ø 81.8% died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion:
Ø Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown.
Ø The epidemiology of human PCP is unclear yet .
Ø Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
Ø The results of the present study demon stated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
Ø Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
Ø Previous studies demonesrate that CMV infection increases a risk of PCP, it is supported by the present stusy . This may be because CMV might modify the host immune response, leading to immune suppression.
Ø Pre-transplant dialysis was newly identified as a protective factor of PCP in this study. Accordingly, appropriate pre-transplant resolution of uremia would decrease the risk of post-transplant PCP.
Ø But , a long-term pre-transplant dialysis negatively affects the host immune status .
Ø The PCP itself did not affect the risk of of acute rejection and de novo DSA production. But PCP was significantly associated with overall graft failure. infections such as CMV, BK virus, and hepatitis C virus, and Pseudomonas aeruginosa, affect allograft dysfunction by modulating non-immunological factors such as hemodynamic change in addition to immunological factors . In this study , PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Ø Mortality risk was elevated in patients with PCP.
Ø prophylaxis against PCP may be strongly recommended.
Ø According to the KDIGO guideline, it is recommended that all recipients receive prophylaxis against PCP for 3–6months after transplantation .
Limitations of this study.
Ø First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively.
Ø Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Ø Lastly, the present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion:
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
Q2- What is the level of evidence provided by this article?
This article analyses the impact of Pneumocystis Jirovecii pneumonia on the outcomes of kidney transplantation.
INTRODUCTION
Post transplant infections play a major role in deciding transplant outcomes. Even with more and more advancement in immunosuppression and newer management protocols, the incidence of infections has remained steady over last 15 years. Rather with advent of more potent immunosuppression, risk of infections, viral, fungal and bacterial has increased.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
impact of PCP on kidney transplant outcomes, including graft failure and rejection were evaluated in this study.
METHODS
This is a retrospective observational study which included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
Transplant outcomes:
1. Death-censored graft failure defined as a return to dialysis or kidney re-transplantation.
2. All-cause mortality.
RESULTS
1. Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
2. The median time to the development of PCP was 5.2 months
3. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
4. PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 [1.14–8.26]); P = 0.027).
5. All-cause mortality was higher in the PCP-positive group than in the PCP-negative group.
6. Pre-transplant dialysis was newly identified as a protective factor of PCP
DISCUSSION
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured. It is necessary to investigate whether the long term effect of PCP on allografts is due to the infection alone or with chronic inflammatory process and other unknown mechanisms.
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. However, occurrence of PCP was significantly associated with overall graft failure.
Mortality risk and is significantly increased whereas graft outome becomes poor in patients with PCP. Hence, prophylaxis for PCP after transplantation is recommended for all patients for a period of 3-6 months post transplantation.
LIMITATIONS
1. Reterospective study makes it difficult to demonstrate, cause and effect definitively.
2. The definition of prophylaxis against PCP was 1 month, which is less than the recommended guideline of 3-6 months.
3. the study could not identify the mechanisms underlying the risk and subsequent effect of PCP.
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts .
The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
Certain infections such as cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods Data collection and definitions
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infection
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected.
The development of de novo donor-specific antibody (DSA) was defined as any newly developed anti-HLA class I or II antibody.
Results Baseline characteristics and risk factor of PCP
The median duration of follow-up was 6.2 years.
4.5% experienced PCP after kidney transplantation.
The median time to the development of PCP was 5.2 months and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
PCP and transplant outcomes
13.2% patients developed death-censored graft failure.
univariable and multivariable analyses showed a significant relationship between PCP and graft failure.
Although the acute T cell-mediated and antibody-mediated rejection episodes or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted, the PCP-positive recipients had a higher risk of deathcensored graft failure than the PCP-negative recipients.
The clinical information on the PCP-positive patients with graft failure.
All the patients were male and had no history of prophylactic antibiotics usage after transplantation.
88.9% experienced acute kidney injury according to the Kidney Disease Improving Global Outcomes criteria and (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
The outcomes did not differ between PCP-positive and –negative groups .The results suggest that different graft failure rates might not be attributable to the conventional immunological transplant episodes, but might be related with non-immunological factors such as concurrent acute kidney injury.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group .
The PCP-positive group had a higher risk of mortality than the PCP-negative group.
81.8% died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion
The results of the present study demonstrated that
male gender and CMV positivity were risk factors associated with PCP
use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs. Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
CMV infection increases a risk of PCP
Pre-transplant dialysis was newly identified as a protective factor of PCP. Uremic condition is linked to altered immunological responses appropriate pre-transplant resolution of uremia would decrease the risk of post-transplant PCP.
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. Nevertheless, occurrence of PCP was significantly associated with overall graft failure.
PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Certain PCP-positive patients had concurrent acute kidney injury and half of them did not achieve the recovery from this condition, which might leave the grafts with non-immunological damages.
However, through non-immunological pathways, infections may also induce allograft injury by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8 These proinflammatory cytokines are known to be upregulated in patients with PCP.
81.8% patients died within 3 months after diagnosis of PCP infection. The causes of death in these patients were either PCP itself or the other infection superimposed on PCP.
There are some limitations of this study .
First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively. Nevertheless, the study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes. Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Lastly, the present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure. The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
level of evidence retrospective analysis level of evidence III
·Summmary of Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcomeIntroduction
· PCP remains a serious opportunistic infection in heavily immunocompromised patients who are not taking chemoprophylaxis.
· The organism
· A group of fungi named Archi ascomycetes has only one copy of nuclear ribosomal RNA and a fragile cell wall and contains little or no ergosterol.
· Transmission of infection
· P-jirovecii can not be cultured in vitro.
· Human hosts can be infected with more than one strain of pneumocystis jirovecii, so the possibility that infection can be acquired on multiple occasions.
· Drug treatment
· The main drug classes used for treatment and prophylaxis of PCP included antifolate drugs ,diamines, atovaquone, and macrolides.
· TMP-SMX is as effective as interim pentamidine for therapy.
· TMP-SMX is the most effective chemoprophylaxis.
· Other medications for the treatment of PCP are Sulfadiazine plus pyrimethamine ,atovaquone, clindamycin plus pyrimethamine e, trimetrexate, dapsone, and aerosolized pentamidine.
· Medication effective for prophylaxis are :
· Dapsone. Dapsone-trimethoprim, atovaquone, aerosolized pentamidine, pentamidine, and clindamycin-primaquine are not effective for prophylaxis.
· PCP prophylaxis for HIV -infected patients with CD4 less than 200 cell/min.
· 80/400 mg TMP-SMX daily appears to be equally effective and associated with fewer side effects than 160/800 mgdialy.
· Tolerability may improve with lower doses of the intermittent regimen.
· Treatment of PCP
· The mortality rates decrease to 5-15%recently as earlier diagnoses and treatment of the PCP infection and the introduction of corticosteroids to patients with moderate to severe PCP if oxygen is less 70 mmHg.
· Sulpha drugs are a structural analogy of PABA and inhibit DHPS.
· In the only non-crossover trial TMP-SMX was associated with better survival than pentamidine survival than pentamidine.
· Adverse affect occurs after 7 days of therapy including rash,fever,leukopenia,hepatotoxicity, and interstitial nephritis plus renal calculus formation.
· Anaphylactic reaction and pancreatitis can occurs.
· Trimethoprim can cause hyperkalemia
· Pentamidine to avoid serious fatal complications slowed and administrated slowly by intravenous infusion .
· Inhaled pentamidine can be used for therapy but it has poor efficacy .
· Side effects of pentamidine:
· Glommular and tubular damage.
· Toxic to the pancreas that can result in hypoglycaemia .
· leukopania
· prolong QT interval
· alternative for the for the TMP-SMX and pentamidine :
· dapsone -pentamidine ,clindamycin -primaquine and atovaquone
· .Atovaquone is a good alternative to TMP-SMX for patients with mild disease who can not tolerate TMP-SMX..duration in HIV-negative is 2 . and HIV positive is 3 weeks.
· Sulphonamide Resistance
· In a retrospective study, TMP-SMX resistance was more than twice as likely in blood cultures from HIV patients receiving TMP-SMX compared to patients not receiving this prophylaxis . Sulfa Resistance
· An organism is caused by a mutation in the primary sequence of the DHPs gene .
· Two recent results reported the double DHPs mutation.Th55Ala and Pro57 ser result in an absolute requirement for PABA.
· The clinical significance of DHPs mutation, with regard to response to prophylaxis and therapy using asulfa based regimen has been controversial.
· There is evidence to suggest the contributory role for DHPs mutation in breakthrough PCP in patients using alternative sulfa prophylaxis .
· DHFR Resistance In Trimethoprim in vitro , the combination of trimetrexate and sulfamethoxazole may be amore potent combination than trimethoprim plus sulfamethoxazole. However, no clinical data support this. Limitation of this study
· The absence of a culture system precluded standard susceptibility testing and limited, the understanding of many fundamental aspects of the organism.
· Absence of definition of clinical failure
· High incidence of adverse effects by the treatment of PCP which included fever caused by infection or treatment.
· Non adherence is presumed failure of prophylaxis may be difficult to access. Although several studies have reported DHFR mutation ,there is so far no evidence that the wide spread use of TMP-SMX have caused emergency of clinical significant resistance to DHFR inhibitors.
· Atovaquone
· It has high number of mutation about 7 which can be explained by ahigh mutation rate and impaired proof reading of mitochondrial genes.
· Survival the same inpatients with or without mutation
· Pentamidine and clindamycin-primaquine:
· are used for presentation and treatment of PCP but possible resistance mechanism have yet to be discussed and reported.
· Conclusion
· Mutation in sulfa and atovaquone drug resistance in P.jirovecii as a result of selective pressure by the widespread use of PCP prophylaxis .
· But there is no firm evidence that DHPs mutation in result in significant resistance to high dose sulfa thearpy.
· Investigation into the mechanism of drug resistance and identification of new moleucular target are continuing..
· These data is crucial for further understanding of the infection and will enable identification of new polymorphic regions and drug targets and may eventually also lead to the development of aculture system. leve evidence 5
Introduction
Infection is an important risk factor of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts. P. jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts. Among kidney transplant patients without prophylaxis, the incidence of P. jiroveciipneumonia (PCP) ranges from 0.6 to 14%, and a morality of 50% despite aggressive antibiotic therapy. This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods
It was a retrospective observational study, which included 1827 patients who had kidney transplantation at Seoul National University Hospital, from January 2000 to December 2017. Patients under 18 years and patients who received two simultaneous transplants were excluded, and consequently 1502 patients were finally included. Data from the patients was collected from electronic medical records. Demographic characteristics included age, weight, gender, height and body mass index were collected. Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure and comorbidities such as hypertension and diabetes was evaluated. The Abo and HLA compatibility was also evaluated and immunosuppression therapy was determined. PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest CT and PCP positive PCR on sputum or bronchoalveolar lavage fluid. Patients were prescribed oral prophylaxis for the first 4 weeks after transplantation, trimethoprim/sulfamethoxazole.
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney re-transplantation.
The secondary outcome was all-cause mortality. All patients were followed up until graft failure or March 2018. Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection and interstitial fibrosis and tubular atrophy were collected. Protocol biopsies were performed at zero-time, on the 10thday and 1 year after transplantation, and every year thereafter.
Results
Of the 1502 patients, 68 patients experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 persons-years. The median time to the development of PCP was 5.2 months, and 79.4% of the cases developed during the first year after transplantation. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Among the 68 PCP positive patients, 9 patients developed death-censored graft failure. The PCP-positive recipients had a higher risk of death-censored graft failure than PCP-negative kidney transplant recipients. 28 of the PCP positive patients had other infections concurrently, and 8 of these patients died. All-cause mortality was higher in the PCP-positive group than the PCP-negative group. The PCP-negative group had a higher risk of mortality than the PCP-negative group. The most common cause of death of the PCP-positive patients was acute respiratory distress syndrome related with PCP.
Discussion P. jiroveciiis an opportunistic fungus, and its lifecycle remains unknown as it cannot be cultured. It is imperative to further understand the role of PCP on allografts. The results of the study demonstrated that the male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics reduced the risk of PCP. The occurrence of PCP increased the risk of long-term graft failure. As PCP was associated with graft failure and overall mortality, intensive treatment and prophylaxis is recommended after kidney transplantation. The results also noted that PCP did not increase the risk of rejection after infection. This may be because non-immunological factors may be the cause of the findings. It was reported that the mortality risk was elevated in patients with PCP. Therefore, considering these findings, prophylaxis against PCP may be recommended. Further research is required on the definitive dosage and duration of prophylaxis.
Limitations
The limitations of the study include the retrospective approach and the current definition of the prophylactic antibiotics was one month, which is shorter than the guideline recommendation.
Level of Evidence:
This is a retrospective comparative study, therefore, the level of evidence is level III
INTRODUCTION
The pneumocystis jerovicii which is opportunistic infection that cause severe pulmonary infections in immunocopmromised patients .
The incidence of PCP varies from 0.6% to 14% among kidney transplant recipient who on not prophylaxis ,with mortality rate of up to 50%
all previous studies showing that PCP increase the mortality but with clear effect on graft function or graft survival .
In this study we need to know what is impact of PCP on kidney transplant outcome including graft failure and rejection. METHOD
This study is retrospective observational analysed 1502 adult patients post kidney transplanted at seoul national univrersity hospital .this number of patients after exclude simultaneous kidney –liver or kidney –pancreas transplantation and also exclude who age under 18 years.
The study compare graft and survival outcome between PJP negative and PJP positive groups between January 2006 to December 2017( median duration of follow up 6.2 years). RESULT
In the period of 6.2 years in total of 1502 patients 68 patients around 4.5% have affected by pneumocystis jerovecii pneumonia with an infection rate of 6.8 case per 1000 person in years.
The median time to the development of PCP was 5.2 months (interquartile range, 3.9–
10.0 months), and 79.4% of cases developed during the first year after transplantation. There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen ,HTN,and CMV positivity. After adjustment for multiple covariates, CMV positivity and when we not using prophylactic antibiotics all are associated with increasing risk of pneumocystis jerovecii pneumonia.
Graft failure in positive PCP was more than negative around 9 patient (13.2%).
Mortality rate was increase in positive PCP than negative PCP with hazard ratio (HR, 10.99).
There is no differences between positive PCP and negative PCP in development of denovo DSA and histopathological changes as interstitial fibrosis ,atrophy and T cell mediated rejections . CONCLUSION
Male,CMV positivity and non using of prophylactic antibiotics are considering risk factors of PCP which is significantly increasing mortality and graft loss.
Introduction:
An opportunistic Fungal infection “Pneumocystis jirovecii” causes pneumonia (PCP) in immunocompromised cases including kidney transplant recipients.
The incidence rates range from 0.6-14% with a mortality rate up to 50% even with treatment in patients without PCP prophylaxis.
Methods:
This was a retrospective observational analysis of the effect of PCP infection on long term graft survival in kidney transplant recipients.
A total 1827 patients included with 325 exclusions leading to review of 1502 patients who underwent kidney transplant at Seoul National University Hospital from 2000 to 2017.
Two groups: PCP-positive, and PCP-negative groups were made, and graft outcomes and patient survival were compared between them.
Results:
1502 patients were followed for median of 6.2 years. out of which 68 (4.5%) patients developed PCP. Median time was 5.9 months to infection, out of which 79% developing PCP during their first year.
Risk factors for PCP were as follows.
CMV positivity,
non-use of prophylactic antibiotics,
and male gender.
In PCP-positive group 13% developed graft failure pointing towards increased risk of graft failure (hazard ratio 3.1). but important point was that all PCP-positive patients developing graft failure were males and had no PCP prophylaxis in the past. They also had associated acute kidney injury (AKI) at time of admission.
Increased risk of mortality was seen in PCP-positive group (hazard ratio 11) as compared to the PCP-negative group, with up to 80% mortality within 3 months of developing PCP.
Protective factors were use of prophylactic antibiotics, and pre-transplant dialysis. No difference was observed with respect to donor specific antibody (DSA) formation, acute rejection (suggesting non-immunological cause of graft failure), or interstitial fibrosis and tubular atrophy between the studied 2 groups.
Limitations:
Retrospective study,
Duration of prophylactic treatment for PCP was not clear,
Dose of prophylactic antibiotics in the study was not clear.
Inability to ascertain mechanisms underlying the risk and effects of PCP because observational nature of the study.
To conclude, PCP in renal transplant recipients increases risk of graft loss and mortality, and hence adequate measures should be taken to prevent (by using oral prophylactic antibiotics) and aggressively treat PCP.
2. What is the level of evidence provided by this article?
This is level 3 evidence: because it was “retrospective case control study”.
This is a retrospective observational study analysed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After excluding paediatric patients (under 18 years old) and those who received simultaneous kidney–pancreas or kidney–liver transplants were excluded, the remaining 1502 patients were finally included, and their data were reviewed. The median duration of follow-up was 6.2 years.
Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. Results: A total of 68 patients (4.5%) developed PCP after transplantation. After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Additionally, both univariable and multivariable analyses showed a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31– 8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012), respectively. Also, the PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 [1.14–8.26]); P = 0.027).
The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. All-cause mortality was higher in the PCP-positive group than in the PCP-negative group. However, the PCP event was not related with the subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody-mediated rejection and interstitial fibrosis and tubular atrophy
The article concludes that PJP is a significant risk for kidney transplant recipients and can impact transplant outcomes. The development of PJP was associated with a higher incidence of acute rejection, delayed graft function, and longer hospital stays. The use of prophylactic medications to prevent PJP is an effective strategy to improve transplant outcomes and reduce the risk of infection and improve transplant outcomes.
Graft failure decreased over last decades because of improved immunosuppressive medication, but mortality continued to be the same and the second most common cause of death in SOT is infections.
Pneumocystis jirovecii is an ascomycetous fungus that causes severe pulmonary infection in immunocompromized patients, with incidence ranging from 0,6- 14% in kidney transplant recipients not having PCP prophylaxis with mortality reaching 50% of cases, but the effect of PCP on graft survival and rejection, were not explored.
This retrospective cohort observational study included almost 1500 patients, had a kidney transplant in Seuol University Hospital, form January; 2000 to December; 2017.
Exclusion criteria: patients less than 18 yrs of age, and those receiving other organ with kidney transplant.
Defintions:
PCP infection: was the presence of radiological findings suspicious of PCP detected by a radiologist, combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
CMV positivity: was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture.
TMP/SMX prophylaxis started immediately after transplant and for one month, but no other prophylaxis drugs were used.
All patients maintained on MMF, CNI, and prednisolone, and most of them received induction with either with rituximab or ATG
Methods and outcomes:
All patients maintained on MMF, CNI, and prednisolone, and most of them received induction with either with rituximab or ATG
Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter, or with deterioration of kidney function or when suspecting rejection, and reviewed by renal pathologist.
DSA test defined by the development of a new anti-HLA antibodies against class I and class II.
Primary outcomes:
Death censored graft failure- return to dialysis, or kidney retransplantation.
Secondary outcomes:
All – cause mortality, based on data obtained from the National Database of Statistics Korea, all followed until graft failure or till March;2018.
Statistical analysis:
Scores were created with matching variables including age, gender, donor type, type of pre-transplant dialysis, hypertension, the usage of prophylactic antibiotics, and CMV positivity.
Propensity score matching was performed to account for the imbalance in baseline characteristics between the PCP-positive and -negative groups.
Following propensity score matching, graft survival, overall patient survival, risk of rejection and development of DSA were analyzed using univariable and multivariable, with a P value of 0.05 considered significant.
Results: Risk factors for PCP infection were:
First year post transplant (79.4% of affected cases)
Difference among PCP+/PCP- patients were more significant in males, being on preemptive transplants > peritoneal dialysis > hemodialysis (NOT the duration on dialysis), ABO incompatible, induction with basilximab, and CMV positivity.
The results based on outcomes:
Death-censored graft failure was significantly more among PCP positive patients (P <0.008).
Graft failure (n = 9) All the patients were male and had no history of prophylactic antibiotics usage after transplantation. And experienced an acute kidney injury according to the KDIGO criteria, 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
The risk of occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs, did not differ between PCP+ and PCP- groups.
All-cause mortality was higher in the PCP+ group than in the PCP- group.
81.8% died within 3 months after the PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Prophylaxis against PCP is protective and highly recommended.
Weakness:
Single center prospective study, difficult to demonstrate cause and effect.
The adequacy of dialysis not evaluated in this study for better clarification as a risk factor.
The definition of PCP prophylaxis was one month use of TMP/SMX which is less than the recommendation of 3-6 months.
Observational study could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Strength:
Large number of patients.
Being the first study demonstrate the effect of PCP+ on graft failure and whether related to rejection or IFTA (proved by biopsy) as well as the effect in all-cause mortality.
Conclusion:
The study clearly identifies the risk factors for PCP infection, and the protective effect of PCP prophylaxis.
The study showed that PCP+ has higher mortality, and may be a non-immune related graft failure.
What is the level of evidence provided by this article?
The level of evidence is II, retrospective cohort exposed to PCP as a risk factor, and looking for outcomes.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocom- promized hosts .
The incidence of P. jirovecii pneu- monia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy .
study design,
methods
This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
2.results,
The median time to the develop- ment of PCP was 5.2 months (interquartile range, 3.9– 10.0 months), and 79.4% of cases developed during the first year after transplantation .
The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP .
This may be because CMV might modify the host immune response, leading to immune suppres- sion Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation .
PCP did not increase the risk of any rejection after infection, suggest- ing that non-immunological factors may be the cause underlying the observations .
level of evidenc 3 (retrospective obserivational study).
Aim of the study : This article examines the impact of pneumocystis jirovecii pneumonia (PCP) on kidney transplant outcome.
Introduction :
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts, and its incidence varies from 0.6 to 14% among kidney transplant recipients without prophylaxis. Several studies have investigated the relationship between PCP and mortality, but the effect of PCP on graft rejection and overall graft outcomes has been less-well-explored. Certain infections such as cyto-megalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period, which is a meaningful clinical issue.
Methods and result :
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
Results: Showed that 68 patients (4.5%) developed PCP after transplantation, with positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis being risk factors. The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group, but the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings. With the continued development of immunosuppressive regimens in the past decade, death-censored graft failures have gradually decreased in kidney transplant recipients. .
Conclusion :
PCP is an important factor in relation to the risk of death and graft failure in kidney transplant recipients so appropriate infection prevention and treatment regimens need to be implemented to improve patient and graft survival outcomes which is expected to be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients. . Limitation of the study
Being an observational retrospective study.
The duration of prophylaxis mentioned was >4 weeks unlike what is recommended which is 3-6 month
– What is the level of evidence provided by this article? -Level 3 ( observational retrospective cohort study)
SUMMARY
The incidence of P. jirovecii pneumonia (PJP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy. In this study impact of PJP on kidney transplant outcomes, including graft failure and rejection were evaluated.
This is a retrospective observational study of total 1827 patients who had kidney transplantation and simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded. After a propensity score matching was performed, the graft and survival outcomes were compared between PJP-negative and PJP-positive groups with median duration of follow-up was 6.2 years.
Results
The infection rate was 6.8 cases per 1000 person-years.
Median time to the development of PJP was 5.2 months.
79.4% of cases developed during the first year after transplantation.
Non-use of oral prophylactic antibiotics were associated with an increased risk of PJP.
13.2% patients among PJP-positive recipients developed death-censored graft failure and they had a higher risk of death censored graft failure than the PJP negative recipients.
Increase risk of graft failure was occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs.
All-cause mortality was higher in the PJP-positive group.
Acute respiratory distress syndrome was the most common cause of death related with PJP.
Conclusion-PJP significantly increases both the risks of mortality and graft failure.
Limitation
Observational retrospective study.
Shorter prophylaxis time then recommended.
Level of evidence is 3 retrospective observational study
Summary of the article Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
This is a retrospective observational study, analyzed 1502 KTRs at Seoul National University Hospital between 2000 and 2017 where the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. The study aimed at answering the question: Could PCP be implemented to address subsequent immunological complications?.
Pneumocystis jirovecii in KTR: 1. Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocom- promized hosts. 2. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortal- ity of up to 50% despite aggressive antibiotic therapy. 3. Certain infections such as CMV and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
Results and Discussion Results: 1. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP. 2. Male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP. 3. Pre-transplant dialysis was newly identified as a protective factor of PCP (Uremic condition is linked to altered immunological responses). 4. The study’s analyses showed a significant relationship between PCP and graft failure. 5. The PCP-positive recipients had a higher risk of death- censored graft failure than the PCP-negative recipients. 6. No difference between PCP-positive and negative groups regarding the risk of subsequent occurrence of rejection, de novo DSAs, interstitial fibrosis and tubular atrophy. 7. All-cause mortality and mortality rate were higher in the PCP-positive group. The most common cause of death was acute respiratory distress syndrome related with PCP. Discussion: 1. Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation. 2. Previous studies have shown that CMV infection increases the risk of PCP which might be explained by modification of host immune response by CMV that alters the T cell response and aggravate pulmonary impairment during PCP activation. 3. PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations(overall graft failure). 4. The proinflammatory cytokines such as IL-1, IL-6, and IL-8 are known to be upregulated in patients with PCP and may also induce allograft injury.
Limitations of the study
1. It is a retrospective study making it difficult to demonstrate cause and effect definitively.
2. The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation and might increase overall risk of PCP in study subjects.
3. The present observational study design could not determine the mechanisms underlying the risk and sub- sequent effect of PCP. Strengths of the study 1. The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
The level of evidence provided by this article:
This is a retrospective study with level of evidence grade 3.
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in KTR.
Pneumocystis jirovecii is an opportunistic infection affects immunocom-promized patients .
It occurs in atound 0.6 to 14% among of KTR with high mortality rates of up to 50%.
Its long term effect on graft survival is still unclear.
This is a retrospective observational study on 1502 KTR comparing graft and survival outcomes between PCP-negative and PCP-positive groups.
*Methods
– The study design was approved by the institutional review board of Seoul National University Hospital
-1502 KTR from January 2000 to December 2017.
*Data collection
-Age, gender, height, weight, and body mass index.
– prior history of transplantation, the type and duration of dialysis, past medical history.
-ABO compatibility and the number of HLA mismatches, Immunosuppressive therapy including induction .
-PCP infection determined by CT findings, positive PCR, direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
-Initial use of prophylactic antibiotics with trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
-primary outcome was death-censored graft failure, secondary outcome was all-cause mortality.
-Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter.
-Additional kidney biopsies were done if indicated according to graft function with monitoring if DSA.
*Results
-4.5% of patients had PCP after kidney transplantation,79.4% of cases developed in the first year after transplantation.
-CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
-13.2% of PCP-positive patients developed death-censored graft failure.
-PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients.
-11-patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and negative groups, respectively.
-The PCP-positive group had a higher risk of mortality, 81.8% of deaths occurred within 3 months after the occurrence of PCP due to cute respiratory distress syndrome related with PCP.
*Discussion
-Long term effect of PCP on allografts needs more studies and weather this long term effect is related to the infection alone or with chronic inflammatory process and other unknown mechanisms is still unclear.
-Current study showed that male sex and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
-CMV infection affects the T cell ,which is important factor affecting the vulnerability to and resolution of PCP, and alteration of the T cells and its aging by CMV might aggravate pulmonary impairment during PCP.
-Pre-transplant dialysis was newly identified as a protective factor of PCP.
-PCP did not increase the risk of any rejection after infection, so a non-immunological factors may be the cause underlying the observations.
-Mortality risk was higher in patients with PCP and the rIsk is highest within the first 3 months of infection therefore
prophylaxis against PCP may be strongly recommended for 3–6 months after transplantation.
But still definitive guidelines on the duration and dosage of PCP prophylaxis are not available
*Limitations
– a retrospective study, making it difficult to demonstrate cause and effect definitively.
-prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (3–6 months)
-The duration of antibiotic prophylaxis might differ between centers.
-present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
What is the level of evidence provided by this article?
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients. Acute phase toxicity in patients with PCP is well established , but there is a lack of data on the effects of PCP on long-term graft outcome. Pneumocystis jirovecii is an opportunistic pathogen which causes pulmonary infection in immunocompromized with incidence from 0.6 to 14% among kidney transplant recipients without prophylaxis. The mortality in spite of aggressive antibiotic treatment is 50%. The study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methodology
It was a retrospective observational study with 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. The graft survival & outcomes were compared between PCP-negative and PCP-positive groups. Those under age 18 years and those receiving combined kidney and pancreas transplant were excluded. Thus total no was 1502.
Protocol biopsies at Day 0. 10 and 365
Results
Follow up time 6 years and 2 months
A total of 68 patients experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months & 79.4% of cases developed during the first year after transplantation.
CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
There was a significant relationship between PCP and graft failure, with HRs of 3.34 and 3.33respectively.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
Discussion
The use of ATG and the presence of CMV infection increases the risk of PCP
The occurrence of PCP itself did not affect the risk of following development of acute
rejection and de novo DSA production
Conclusion
· PCP is associated with higher risk of graft loss and mortality.
· Risk of PCP is high in male sex and with non use of antibiotics
· More trials needed on the use of prophylaxis in kidney transplant recipients
What is the level of evidence provided by this article?
Introduction : Pneumocystis jirovecii is an opportunistic pathogen that causes serious lung infections in immunocompromised individuals. Incidence of P. jirovecii pneumonia (PCP) ranges from 0.6 to 14% in unpreventive kidney transplant recipients despite aggressive antibiotics. It has a mortality rate of up to 50%. Methods: A retrospective observational study was conducted on 1,502 adult kidney transplant patients at Seoul National University Hospital from 2000 to 2017. PCP positive group. Results: Average follow-up was 6. 2 years (interquartile range 3.0-9.6 years; maximum 18.3 years) Of 1502 patients, 68 (4.5%) had pneumocystis pneumonia after kidney transplant, with an infection rate of 6.8 cases per 1000 person-years Median time to onset of PCP was 5.2 months (interquartile range 3.9-10.0 months), 79.4% of cases occurred within 1 year of transplantation Significant difference between PCP-positive and negative patients Gender; Regarding pre-transplant dialysis type, ABO incompatibility, desensitization therapy, induction therapy, hypertension and CMV positivity. Death-screened graft failure occurred in 9 (13.2%) of 68 PCP-positive recipients. ACox multivariate analysis found that positive cytomegalovirus and lack of early oral antibiotic prophylaxis were risk factors for PCP after transplantation. There was a higher hazard ratio for transplant rejection in the PCP-positive group [adjusted hazard ratio (HR), 3.1 (1.1). 14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68-32.0). 80); P<0.001] than the PCP negative group. However, the PCP events were not associated with subsequent development of de novo donor-specific antibodies or pathological changes such as T-cell or antibody-mediated rejection, interstitial fibrosis, and tubular atrophy Conclusion:
PCP has long been a risk factor. -Term transplant rejection and mortality with or without rejection. Therefore, proper prevention and treatment are necessary to avoid the side effects of PCP transplantation.
PJP is well-known as an important cause of morbidity and mortality in renal transplant recipients.
Acute presentations are well-known regarding the treatment and also prophylaxis. However, the effect on long-term graft and patient survival is not well-known.
this article was for a retrospective observational study to evaluate these long-term effects. the study included 1502 renal transplant patients who were transplanted at Seoul national university hospital in the period between 2000 and 2017. the patients were divided into tow groups of according to having an acute PJP pneumonia.
after proper matching, graft and patient survivals were compared in both groups of patients. the results were as following :
1- 68 patients (4.5 %) developed an acute PJP pneumonia. there were 2 identifiable risk factors for having this disease. the 1st was +ve CMV status and the 2nd was lack of oral antibiotic prophylaxis.
2- graft failure was more in the +ve group with an adjusted hazard ratio of 3.1, as compared with the -ve group.
3- mortality was more in the +ve group with an adjusted hazard ratio of 11, as compared with the -ve group.
3- there was no relation between PJP and subsequent development of de novo DSA or pathologic changes as T-cell mediated rejection, interstitial fibrosis or tubular atrophy.
Conclusions :
1- PJP is a risk factor for long-term graft failure and mortality that are independent of rejection.
2- appropriate prophylaxis and treatment are still necessary for PJP
What is the level of evidence provided by this article?
I like your detailed summary and analysis.
Why would you label this as level 3?
Please use bold or underline for headings and sub-headings to make it easier to read.
Introduction
In patients with a functional graft, infection is the second leading cause of death after CVS illness. Data on the immunological effects of particular infectious illnesses in transplant recipients is scarce. Hence, more research on infectious posttransplant occurrences is required to enhance survival rates. Pneumocystis jirovecii is an opportunistic pathogen that causes severe lung infections in immunocompromised patients, with a 50% mortality risk in those who do not receive prophylactic antibiotics and even after vigorous antibiotic therapy. In this study, the effects of PCP on kidney transplant outcomes, such as graft failure and rejection, were assessed.
Methods
The 1502 adult patients who received kidney transplants at Seoul National University Hospital between 2000 and 2017 were the subject of this retrospective observational study. Following the use of propensity score matching, the graft and survival results of the PCP-negative and PCP-positive groups were compared with a median follow-up of 6.2 years.
Results
Out of 1502 patients, 68 (4.5%) developed PCP after KT, with a 6.8 case/1000 person-year infection rate. The average time it took for PCP to manifest was 5.2 months, and 79.4% of cases appeared within the first year.
Regarding gender, pre-transplant type of dialysis, ABO-i, desensitization therapy, induction regimen, HTN, and CMV positivity, there were significant variations between PCP-positive and -negative patients. CMV positive and not using oral prophylactic antibiotics were linked to an elevated risk of PCP when several variables were adjusted for.
13.12% of the 68 PCP-positive recipients experienced death-censored transplant failure. Compared to the PCP-negative group, the PCP-positive group showed greater graft failure hazard ratios.
All of the patients were men, and none of them had ever used prophylactic antibiotics following a transplant. Eight out of nine patients (88.9%) developed acute kidney injury throughout the hospitalization period, and four of them (50%) did not have their graft functions fully recovered at release despite responding well to PCP.
Limitations
The first limitation of the study was that it was a retrospective study.
Second, the present definition of prophylactic antibiotics, one month, was shorter than the recommended by guidelines.
Level of evidence Level 3: Observational retrospective cohort study
I like your detailed summary, limitations of study and analysis. Why would you label this as level 3?Is it a retrospective cohort or a case-control study?
Thank you Professor for your comment.
The provided study is a retrospective cohort study looking for risk factors and the outcome of interest, so maybe level of evidence between II and III. I am confused because level of II implies that the study is prospective and not retrospective.
Long term effects of PCP infection on the graft outcome
Summary
· Infections are 2nd cause of mortality among adult transplant recipients after cardiovascular causes of death.
· PCP is a well-known cause of post-transplant morbidity and mortality in kidney transplantation.
· Risk factors as strong IS use, lack of chemoprophylaxis and concomitant CMV infection.
· Dialysis and improvement of uremic state can decrease the risk of post-transplant PCP infection, but prolonged duration can worsen the outcome.
· The current study aimed to Compare between PCP positive and negative cases regarding long term graft survival (based on allograft biopsy done every year to detect TCMR, ABMR and IFTA).
· During acute infection, it has deleterious effects on the graft that can be related to immunological and none immunological factors, in addition to the upregulation of cytokines.
· However, the long-term outcome needs to be evaluated. PCP was associated with worse graft outcome (but not explained by more rejection episodes or increasing IFTA).
· PCP was diagnosed by CT chest and identification of the organism by IF staining and PCR.
· KDIGO recommends standard prophylaxis for 3-6 months against PCP with SMX-TMP.
· Points of weakness: retrospective, prophylactic chemotherapy was given for only one moth (while standard recommendations is to give 3-6 months)
· Points of strength: large number of cases,
Level of evidence: retrospective cohort (level III)
I like your detailed summary, weaknesses and strengths of study and analysis.
Why would you label this as level 3?Is it a retrospective cohort or a case-control study?Typing whole sentence in bold or capitals equals to shouting !
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome. Introduction: Still cardiovascular diseases is the most common cause of death post kidney transplant with functioning graft, followed by infection, one of these infection is Pneumocystis jirovecii which is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts, the incidence of PJP is increasing up to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy, as well known cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early post-transplant period and in this study they evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection. Methods. This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups with median duration of follow-up was 6.2 years. Results: -The infection rate was 6.8 cases per 1000 person-years and the median time to the development of PCP was 5.2 months with 79.4% of cases developed during the first year after transplantation. -CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP. -9 (13.2%) patients among 68 PCP-positive recipients developed death-censored graft failure and the PCP-positive recipients had a higher risk of death censored graft failure than the PCP negative recipients. –The cause of the elevated risk of graft failure are occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs. –All-cause mortality was higher in the PCP-positive group than in the PCP-negative group and the most common cause of death was acute respiratory distress syndrome related with PCP. Conclusion. Male gender, positivity for CMV, and non-use of oral prophylactic antibiotics are considered risk factors of PCP in the kidney transplant cases and PCP significantly increases both the risks of mortality and graft failure. Level of evidence:3 (Retrospective observational study).
A retrospective study conducted in S. Korea between years 2000 and 2017 to verify the mortality and allograft dysfunction incidence associated with PJP infection post transplantation. 1502 transplant patients had their transplant performed in Seoul university hospital, were surveyed for post-transplant PJP infection incidence and allograft and patients’ survival were compared between PJP positive and PJP negative patients. Study conclusions:
Patients’ mortality was higher in PJP infected compared to Non PJP infected. The increasing mortality rate was attributed to the fungal infection itself or to other superadded infections.
Allograft survival was compromised in PJP infected patients, however, there was no increased incidence of rejection or production of DSAs post infection, speculating that its non-relevant to immunological derangement and heightened risk of rejection. Non immunological factors for allograft failure were suggested by this study, as PJP infection is linked to acute kidney injury with lingering progressive deterioration of allograft function consequently. Similarly, inflammatory cytokines might be crucially inflicting allograft function, such as IL1, IL6 and IL8 are augmented by PJP infection causing inflammation and fibrosis on long term course post PJP infection. Risk factors:
CMV co-infection was main risk factor for PJP infection, owing to its role in modulating and suppressing cell mediated immunity and C4D lymphocytes in particular predispose to fungal infection of PJP.
Other risk factor was the lack of prophylactic anti-PJP, which is against the general recommendation of CDC to have 3-6 months prophylactic protocol. Limitation of the study:
1] Observational retrospective study.
2] prophylaxis protocol considered during the study period was for 1 month, falling shorter than the recommendation of 3-6 months, portending higher risk of PJP.
3] The mechanism and risk of PJP infection can’t be assessed properly given the retrospective nature of the study. Level of evidence 3
Immunosuppression have been developed. However, infections have been considered as an important factor (second cause ) of death after renal transplantation.
○ PCP incidence is about (0.6 – 14 ) %
○The aim of this study is to evaluate the relation between PCP and renal transplantation outcomes (especially on the graft failure and graft rejection)
Methods
○The study was in Seoul National University Hospital.
○This is a retrospective observational study
○The total number of patients was 1502
○It was performed between 2000- 2017
Criteria of excluding
○Age less than 18 years
○Pancreatic and liver co-transplantation
○The protocol of graft biopsies was performed to identify: (acute T cell mediated rejection- antibodies mediated rejection- interstitial fibrosis and tubular atrophy)
Results
○Median duration of the following up is 6.2 years
○68 patients of 1502 (4.5%) had PCP
○The median time to PCP development was 5.2 Months. But 79.4% was in the first year.
○Risk factors for PCP occurrence after kidney transplantation
Female
ABO incompatibility
Desensitization therapy
Induction therapy
High blood pressure
CMV infection
Pre-transplant dialysis is a protective factor (It will decrease the uremia). Otherwise, long term pre-transplant dialysis negatively affects the host immune system.
GRAFT FAILURE
○9of 68 patient (positive PCP) 13.2% have graft failure (univariable and multivariable analysis showed significant relationship between PCP and graft failure.
○From those who developed graft failure (9), eight of them had AKI
Therefore, graft failure might not be attributed to the immunological factors but might be related to non immunological factors as AKI
○On the other hand, the occurrence of PCP itself did not affect the risk of following development of acute rejection- De novo DSA.
MORTALITY
○mortality was higher 11(16%) in PCP POS compared to (11%) IN PCP neg.
81% of them was happened during the first 3 months.
LIMITATIONS
Retrospective study
Only one month of prophylaxis
Strengths
The first study of the relation between PCP and outcomes mentioned above.
Recommendations
Prophylaxis for PCP is recommended but the duration still controversial.
Please summarise this article.
-Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts .
-Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts .
– The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy .
-It is retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas
or kidney–liver transplants (n = 65) were excluded. The remaining 1502 patients were finally included and their data were reviewed.
-The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
-The occurrence of PCP increased the risk of long-term graft
Failure.
-Intensive treatment and prophylaxis of PCP is recommended after transplantation.
-Pre-transplant dialysis was newly identified as a protective factor of PCP. Uremic condition is linked to altered immunological responses.
-The study showed that PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
– Mortality risk was elevated in patients with PCP.
-According to the KDIGO it is recommended that all recipients receive prophylaxis against PCP for 3–6months after transplantation . Limitation :
-it was a retrospective study, making it difficult to demonstrate cause and effect definitively.
-The duration of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation .
-The study design could not determine the mechanisms underlying the risk and subsequent effect of PCP. What is the level of evidence provided by this article?
Level 3
I like your detailed summary, limitations of srudy and analysis.
Why would you label this as level 3?
Please use bold or underline for headings and sub-headings to make it easier to read.
summarise of Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome Introduction
· Infection is the second cause of death after CVS disease in patients with a functioning graft.
· There is little data on immunological outcomes after specific infectious diseases in the transplant recipient.
· Further studies of posttransplant infectious events are therefore needed to improve survival outcomes.
· Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized patients.
· 0.6 -14% incidence of pneumonia in p.j.
· 50% mortality rate in kidney transplant recipients without prophylaxis and even after aggressive antibiotics therapy.
· This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
· Study design retrospective observational study included 1827 patients who had a kidney transplants at Seoul Natuval University Hospital from jan2000 to dec 2017.
· Transplant outcome: the primary outcome was death-censored graft failure defined as a return to dialysis or kidney re-transplantation. And secondary outcome was all-cause mortality.
· Results:
· There are significant differences between PCP -positive and negative patients with response to gender, type of pretransplant dialysis ,ABOI transplant, desensitization therapy, induction regimen, HTN and CMV positivity and non-use oral prophylaxis antibiotics were associated with an increased risk of PCP.
· PCP and transplant outcome: among 68 PCP-positive 13.2% of patients develop death-censored graft failure. There is a significant relation between PCP and graft failure with HR 3.34 and 3.33 % respectively.
· The result suggests that different graft failure rates might not be attributed to the conventional immunological transplant episodes but might be related to non immunological factors such as concurrent acute kidney injury.
· The most common cause of death was acute respiratory distress syndrome related to PCP.
· Discussion :
· PCP is relatively common after kidney transplantation, its clinical implication especially in relation to graft outcome has not been evaluated.
· The result of the study found that male gender and CMV positive were risk factors associated with PCP and the use of oral prophylactic antibiotics seem to prevent the risk of PCP.
· CMV infection increases the risk of PCP as might modify the host immune response leading to immunosuppression.
· Pre-transplant dialysis was newly identified as a protective factor of PCP,.however term pre-transplant dialysis negatively affect host immune status .
· Limitation of the study:
· 1-Retrospective study making it difficult to demonstrate the cause and effect definitively.
· 2-definition of prophylactic antibiotics 1 month which was shorter than the guidelines recommendation (3-6)month.
· 3-observational study design could not determine the mechanism underlining the risk and subsequent effect of PCP.
· Conclusion:
· Risk factors of PCP in kidney transplant cases with the male gender. positively for CMV, and non-use of oral prophylactic antibiotics.
· PCP significantly increases both the risk of mortality and graft failure. evidence level 3
● Infection is an important risk factor of death in kidney transplant recipients
● Pneumocystis jirovecii is an opportunistic pathogen causes severe pulmonary infection in immunocopromized hosts
● The incidence is 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy
● This study evaluates the impact of PCP on kidney transplant outcomes, including graft failure and rejectionm
Methods
● A retrospective observational study
● 1827 kidney recipients at Seoul National University Hospital
● From January 2000 to December 2017. ● Excluded Patients :
☆ under 18 years old
☆ Simultaneous kidney–pancreas or kidney–liver transplants
● 1502 patients were included
Data collection and definitions
● Data from the kidney transplant recipients were collected from the electronic medical records.
● PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomog-raphy combined with PCP positivity in sputum or bronchoalveolar lavage fluid.
Transplant outcomes
● The primary outcome was death-censored graft failure
● The secondary outcome was all-cause
mortality
Results
● The median duration of follow-up is 6.2 years (3.0–9.6 years )
● 4.5% experienced PCP after Kidney Tx
● The median time to the development of PCP was 5.2 months
● 79.4% developed during the first year after transplantation.
● Factors associated with an increased risk of PCP :
☆ CMV positivity
☆ The non-use of oral prophylactic
☆ Male gender
● 13.2% of patients with positive PCR developed death-censored graft failure.
● 16.2% , 11.0% and 28.6% died in the PCP-positive , negative groups,and PCP-positive with concurrent infection respectively.
● 81.8% died within 3 months after the occurrence of PCP.
● The most common cause of death was acute respiratory distress syndrome
● The occurrence of PCP increased the risk of long-term graft failure and mortality due to Non-immunological factors ( AKI and proinflammatory cytokines ) other than immunological transplant episodes
● Pre-transplant dialysis but not long term dialysis was identified as a protective factor of PCP due to altered immunological responses by Uremic condition
● all recipients receive prophylaxis against PCP for 3–6 months after transplantation
● limitations of study :
☆ A retrospective study
☆ prophylactic antibiotics duration was shorter which could alter the risk of PCP and transplant outcomes.
☆ Mechanisms underlying the risk and sub-sequent effect of PCP could not determine by this study design
# The objective of the study:
Is to determined the effect of PCP on allograft transplant outcomes involving the graft failure and rejection.
# Introduction:
*The common cause of mortality in recipient with functioning kidney is CVD, followed by Infection.
*There is a few information on immunologic outcomes following specific infectious disease in KTR, so more studies in this field are needed.
*PCP is an opportunistic pathogen that lead to severe pulmonary infection in immunocompromized
Patients.
*The rate of PCP varies between (0.6 to 14%) between KTR without prophylaxis, and the deaths is up to 50% in spite of heavy antibiotic therapy treatment.
# Method:
*This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
*After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
*Excluding criteria:
Patients below18 years old , who received kidney–pancreas or kidney–liver transplants .
# The result:
*Out of 1502 patients, 68 (4.5%) experienced PCP post KT, with an infection rate of 6.8 cases per 1000 person-years.
*The median time to the development of PCP was 5.2 months and 79.4% of cases developed during the first year.
*There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-i, desensitization therapy, induction regimen, HTN and CMV positivity.
* After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
*Between 68 PCP-positive recipients, (13.2%) developed death-censored graft failure.
* The PCP-positive group had higher hazard ratios of graft failure than the PCP-negative group.
*All the patients were male and had no history of prophylactic antibiotics usage after transplantation.
*During the admission period, 8 of 9 patients (88.9%) experienced acute kidney injury according to the KDIGO criteria, and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
# The limitation of the study:
*Retrospective study, making it difficult to demonstrate cause and effect definitively.
The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
*The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months),
*The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
# Conclusion:
*Risk of PCP is aggravated in the KT cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
*PCP significantly increases both the risks of mortality and graft failure.
* Prophylaxis may be needed to prevent PCP and subsequent graft failure.
*The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
What is the level of evidence provided by this article?
Introductions:
Infection is second leasing cause of deaths postbkidney trajsplant.
PCP cause increases mortality in 50percent of infected posttransplant patient.
The study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection. Methods Study design and subjects:
retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture. Transplant outcomes
The primary outcome was death-censored graft failure.
The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018.
Data collected for ABMR and CMR. Results Baseline characteristics and risk factor of PCP
After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP . PCP and transplant outcomes :
a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31– 8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012), respectively.
the PCP-positive recipients had a higher risk of deathcensored graft failure than the PCP-negative recipients .
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group.
The most common cause of death was acute respiratory distress syndrome related with PCP. Discussion :
male gender and CMV positivity were risk fir PCP.
use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
Pre-transplant dialysis was newly identified as a protective factor of PCP. Limitation of the study:
First, it was a retrospective study, making .
Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months).
Without prophylaxis, kidney transplant recipients had a P. jirovecii pneumonia (PCP) incidence ranging from 0.6 to 14%, with a mortality of up to 50% despite rigorous antibiotic therapy.
In total, 1827 individuals underwent kidney transplantation at Seoul National University Hospital between January 2000 and December 2017 were included in this retrospective observational analysis. Patients under the age of 18 (n = 260) and those who had simultaneous kidney, pancreas, or liver transplants (n = 65) were both disqualified.
Both univariable and multivariable analyses revealed a substantial association between PCP and graft failure among the 68 PCP-positive recipients, where 9 (13.2%) patients experienced death-censored graft failure.
Although other immunological findings such as interstitial fibrosis, tubular atrophy, and de novo DSA as well as acute T cell-mediated and antibody-mediated rejection episodes were also adjusted, the PCP-positive recipients still had a higher risk of death-censored graft failure than the PCP-negative recipients.
The findings imply that graft failure rates may not be connected to immunological transplant episodes in the traditional sense, but rather to non-immunological variables such as concomitant acute renal damage.
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure.
Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
In KTRs, Infection is the second most common cause of death with functioning graft after cardiovascular disease.
P. jirovecii pneumonia (PCP) one of the opportunistic infection associated with high mortality rate despite treatment. Certain infections increased risk of graft rejection. The effect of PCP on graft function is not well studies.
Aim of the study:
Evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Transplant outcomes Primary outcome : death-censored graft failure defined as a return to dialysis or re-transplantation. Secondary outcome: all-cause of mortality.
Methods Study designRetrospective observational study. Study period: from January 2000 to December 2017. Follow up:All patients were followed until graft failure or March 2018 Included: total 1827 KTRs at Seoul National University Hospital. Exclusion: Patients < 18 years old (n = 260) orpatients received simultaneous kidney–pancreas or kidney–liver transplants (n = 65).
Data collection from EMR. Results for ABO, HLA typing Immunosuppressive therapy were collected. PCP was defined; suspicious of PCP radiologically on chest CT with PCP positivity on PCR or direct immunofluorescence stain of sputum or BAL. Initial use of oral prophylactic antibiotics; defined as a prescription of TMP/SMX for > 4 weeks during the first month after KT. There were no cases with pentamidine or atovaquon for prophylaxis. CMV positivity; defined as > 20 copies/ml on PCR or positive culture Protocol biopsies: done at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter. Additional biopsies: if graft function is deteriorated, or signs of rejection. De novo DSA: as any newly developed anti-HLA class I or II antibody. Propensity score matching was performed to account for the imbalance in baseline characteristics between the PCP-positive and -negative groups. Results: -1502 patients included and followed for median of 6.2 years -PCP infection occurred in 68 (4.5%) KTRs. -Multivariable Cox analysis showed: CMV- positivity and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. -Both univariable and multivariable analyses showed a significant relationship of PCP with graft failure HR of 3.1 – No difference in risk of development of de novo DSA or pathological finding of rejection between PCP-positive and –negative groups – PCP-positive patients had concurrent AKI and half of them did not achieve the recovery which might leave the grafts with non-immunological damages. -All-cause mortality was higher in the PCP-positive group HR of 11.0than in the PCP-negative group 81.8% died within 3 months after the occurrence of PCP. -The most common cause of death was ARDS related with PCP. Conclusions: PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation Limitations: – Retrospective nature of the study, difficult to demonstrate cause and effect definitively. – The overall risk of PCP might be higher in the study as duration of prophylactic antibiotics was 1 month, which was shorter than the recommendations (3–6 months) Strength: -Good follow up period. Level of evidence: Level 3; Observational retrospective cohort study ( started with risk factor PCP positive or negative then looked at outcomes (mortality, graft survival)
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome:
This article is retrospective observational study were kidney transplant patients collected from Seoul National University Hospital from January 2000 to December 2017. This article focus on impact of Pneumocystis jirovecii is on solid organ transplant and it’s outcome. Introduction:
Pneumocystis jirovecii is an ascomycetous fungus and an opportunistic pathogen that can cause morbidity and mortality and increase risk of rejection in immunocompromised patients with transplant.
Risk factors of PCP were there are differences in patients with positive PCP and negative patients; so there’s high risk of PCP in positive patients and those how not receive prophylactic treatment against PCP in respect to other co-morbidity. The maximum time for exposure of patients to infection is 5.5 months post kidney transplant.
The all PCP-positive recipients with graft failure are male and no history of receiving prophylactic antibiotics. Those patients has high risk of death.
PCP positive patients associated with occurrence of rejection, interstitial fibrosis and tubular atrophy and developing of de novo DSA. This study shows patients with CMV infection increase risk of PCP. Where CMV lead to alteration and impair T cell (CD4), function which are expose patients to PCP infection.
Pre- dialysis duration and uremic condition also expose to increase infection because impaired of immunological factors. Occurrence of PCP increase risk of graft failure; also other viral and bacterial infection increase risk of graft failure, however PCP infection itself is not lead rejection but immunological alteration expose patients to rejection. Another non-immunological pathways, infections may also induce allograft injury by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8. Limitations of this study:
First: it was a retrospective study.
Second: the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (3–6 months).
Third: it’s observational study which may not determine the mechanisms underlying the risk and subsequent effect of PCP.
What is the level of evidence provided by this article?
Introduction: Pneumocystis jirovecii, an opportunistic fungal infection, causes pneumonia (PCP) in kidney transplant recipients, with incidence rates ranging from 0.6 to 14% and a mortality rate upto 50% despite treatment in patients without PCP prophylaxis. The effect of PCP on graft rejection and long-term graft results is not known.
Methods: The study conducted was a retrospective observational analysis of effect of PCP on graft rejection and failure in kidney transplant recipients. A total 1827 patients were included, out of which 325 were excluded with final review done for 1502 patients who underwent kidney transplant at Seoul National University Hospital from 2000 to 2017. The patients were divided into 2 groups: PCP-positive, and PCP-negative groups, and graft outcomes and patient survival were compared between them.
Results: 1502 patients were followed up for median time of 6.2 years. 68 out of the 1502 (4.5%) patients developed PCP. Median time to develop PCP was 5.9 months, with 79% developing PCP within first year. Risk factors for PCP included Cytomegalovirus (CMV) positivity, non-use of prophylactic antibiotics, and male gender. 13% of the PCP-positive group developed death censored graft failure (DCGF) pointing towards increased risk of graft failure (hazard ratio 3.1). All PCP-positive patients developing graft failure were males, had no history of PCP prophylaxis, and most had associated acute kidney injury (AKI) at time of admission. PCP-positive group had increased risk of mortality (hazard ratio 11) as compared to the PCP-negative group, and more than 80% died within 3 months of developing PCP. Protective factors for PCP included use of prophylactic antibiotics, and pre-transplant dialysis. There was no difference with respect to donor specific antibody (DSA) formation, acute rejection (suggesting non-immunological cause of graft failure) , or interstitial fibrosis and tubular atrophy between the 2 groups.
Limitations: Retrospective study, lack of clarity regarding duration of prophylactic treatment given, use of non-standardized definition of prophylactic antibiotics in the study (increasing risk of PCP),and inability to ascertain mechanisms underlying the risk and effects of PCP due to the observational design of the study.
To conclude, PCP in renal transplant recipients increases risk of graft loss and mortality, and hence adequate measures should be taken to prevent (by using oral prophylactic antibiotics) and aggressively treat PCP.
2. What is the level of evidence provided by this article?
The level of evidence is level 3: A retrospective case control study
This is a retrospective observational study done inSeoul national center to detecte the effect of PCP on kidney graft survival and the rate of rejection if any .
This study done 1502 patient post RTX , this study was conducted from 2000 to 2007 data obtained from medical records , PCP was daignosed according to imaging and PCR .The aim of the study to know if there is diretc relation between PCP and rejection or survival rate like other CMV and B virus .
usually PCP is an oppertunistic infection with mortality rate of 50% post RTX with morbidity of 0.6 to 14 % .
it is found that PCP is associated with long term graft dysfuction as 4 out of 68 patient remaining with ckd after PCP infection ,adding to that ,This relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
The PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (P = 0.027).
THe study concolude that ,Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. ▪︎PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts. The incidence of P. jirovecii pneumonia (PCP): 0.6 to 14% among kidney transplant recipients without prophylaxisMortality of up to 50% despite aggressive antibiotic therapy.This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Material and methods:
Retrospective observational study Analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. Results:
Median follow-up: 6.2 years68 (4.5%) experienced PCP after kidney transplantationMedian time to develop PCP: 5.2 months79.4% of cases developed during the first year after transplantation.CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.Eleven patients (81.8%) died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.Discussion:
Male gender and CMV positivity were risk factors associated with PCPUse of oral prophylactic antibiotics prevented the risk of PCP.The occurrence of PCP increased the risk of long-term graft failureThis relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.PCP was associated with both graft failure and overall mortalityThat is why intensive treatment and prophylaxis is recommended after transplantation.Limitations :
Retrospective studyProphylaxis given only for 1 month which could be 3 to 6 months
Level of evidence: Level III (retrospective study)
There has been a great improvement in graft survival in the last decades as a result of simultaneous development and improvement in immunosuppressive medication. However, the same could not be said of death that occurs with a functioning graft, and infections have been implication as part of the aetiological causes.
Pneumocystis Jirovechii is an opportunistic pathogen that could manifest with a severe form of respiratory infection, particularly in an immunocompromised host like post-kidney transplant recipients. Its incidence is 0.6% – 14% and with a mortality of about 50% if prophylaxis is not administered
Aim of the study
to evaluate the impact caused by PCP infection on kidney transplant outcomes, like graft failure or rejection.
Method of the study
It is a retrospective observational study done between January 2000 to December 2007 at Seol National University Hospital
Data obtained from electronic medical records of those that had kidney transplants within the above years
PCP was diagnosed with both the Imagin study and PCR level of the organism
Participants, less than 18 years were excluded
PCP prophylaxis was used for just more than one month
Transplant Outcome
The death-censored graft failure was defined as a return to dialysis or kidney transplantation.
The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea.
Results
The median follow-up was 6.2years
4.5% (n=68) of 1502 total participants had PCP
The median time to develop PCP is 5.2months
The CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP infection.
The PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (P = 0.027).
The study also showed that graft failure might be attributable to only immunological issues, but concurrent non-immunological factors like AKI
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group with ARDS as the commonest cause.
Mortality was higher among patients with PCP infection in the study, 9 (81.9%), out of 11 died within three months of diagnosis
The risk of allograft rejection did not increase even among patients with concurrent infections like CMV, BKV, hepatitis C, and Pseudomonas aeruginous
The above is contrary to what previous studies found particularly for CMV.
Limitations of the study
The cause and effect could not be ascertained been a retrospective study
The duration of PCP prophylaxis was shorter than the standard guideline
The study could not establish the mechanism of action of PCP infection
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017 which evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Median duration of follow-up was 6.2 years (IQR, 3.0–9.6 years; maximum 18.3 years).
68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
Median time to the development of PCP was 5.2 months (IQR, 3.9–10.0 months)
79.4% of cases developed during the first year after transplantation.
Significant differences between PCP-positive and -negative patients with respect to
Gendertype of pre-transplant dialysis,ABO-incompatibility,desensitization therapy,induction regimenhypertensionCMV positivityPropensity score matching to mitigate the difference in baseline characteristics between the PCP-positive and -negative groups was done.
Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure
Both univariable and multivariable analyses showed a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31–8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012)
PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients despite acute TCMR and ABMR or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted.
PCP-positive patients with graft failure were all the patients were male and had no history of prophylactic antibiotics usage after transplantation.
8 of 9 patients (88.9%) experienced AKI according to the KDIGO and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
The study evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs and these outcomes did not differ between PCP-positive and –negative groups
Different graft failure rates might not be attributable to the conventional immunological transplant episodes, but might be related with non-immunological factors such as concurrent AKI
11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and PCP-negative groups
28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%)
All-cause mortality was higher in the PCP-positive group,adjusted HR, 10.99
Limitation
retrospective studydefinition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation.duration of antibiotic prophylaxis might differ between centerscould not determine the mechanisms underlying the risk and subsequent effect of PCPConclusion
Risk of PCP is increased in the KT with male gender, positivity for CMV, and non-use of oral prophylactic antibioticsPCP increases both the risks of mortality and graft failureprophylaxis may be needed to prevent PCP and subsequent graft failure. What is the level of evidence provided by this article?
A retrospective observational study (level III)
¤ Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome __________________________ ▪︎This study has evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
◇ Background: ▪︎Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts. ▪︎Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immuno- compromized hosts . ▪︎The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
▪︎While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome. ◇ Method:
▪︎ This a retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. ▪︎ After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. ◇ Results:
▪︎A total of 68 patients (4.5%) developed PCP after transplantation.
▪︎The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. ▪︎ The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy. ◇ Limitation of he study: 1. A retrospective study, making it difficult to demonstrate cause and effect definitively. 2. The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects 3. The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes. 3. The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP ◇ Strength of the study: 1. Informative data. 2. The study achieved its primary purpose: a. By demonstrating the relationship between PCP and transplant outcome b. On the relationship between PCP and transplant outcomes.
◇ Conclusion ▪︎Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
▪︎PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP ▪︎The present study will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients
¤ Level of evidence: Level III (a retrospective study)
▪︎This is a retrospective observational cohort study becaus, it started with risk factor ( PCP positive or negative), then study the outcomes (mortality and graft survival).
▪︎While retrospective cohort studies try to compare the risk of developing a disease to some already known exposure factors, a case-control study will try to determine the possible exposure factors after a known disease incidence.
Infection is an important factor in relation to the risk of death in kidney transplant recipients, the second most common cause of death
The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50%
Methods Study design and subjects
retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded
the remaining 1502 patients their data were reviewed.
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records
Demographic characteristics including age, gender, height, weight, and body mass index were collected.
Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes
Results for both recipient and donor ABO blood groups (ABO) and human leukocyte antigen (HLA) typing were collected to evaluate ABO compatibility and the number of HLA mismatches.
Immunosuppressive therapy was determined, including induction therapy with basiliximab or anti-thymocyte globulin, and calcineurin inhibitors for maintenance therapy. A combination of steroids, mycophenolic acid, and calcineurin inhibitors
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
Initial use of oral prophylactic antibiotics was defined as a prescription of trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
There were no cases with pentamidin or atovaquon for prophylaxis. CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infectionTransplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected.
Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter.
Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months (interquartile range, 3.9– 10.0 months), and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity. After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
With the continued development of immunosuppressive regimens in the past decade, death-censored graft failures have gradually decreased in recipients of both living and deceased kidney recipients.
More information on the causes of mortality unrelated to graft failure is needed to further improve the survival of transplant recipients.
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Despite its clinical implication of these infectious diseases, there is little data on immunologic outcomes after specific infectious disease in transplant recipients.
Several studies have investigated the relationship between PCP and mortality , but the effect of PCP on graft rejection and overall graft outcomes has been less-well explored
Certain infections such as cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
We evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Study design and subjects
The study design was approved by the institutional review board of Seoul National University Hospital
The study design was approved by the institutional review board of Seoul National University Hospital and complied with the Declaration of Helsinki.
1805-173-948) and complied with the Declaration of Helsinki
This retrospective observational study included total 1827 patients who had kidney transplantation.
Seoul National University Hospital from January 2000 to December 2017.
Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded.
The remaining 1502 patients were included and their data were reviewed.
The requirement of informed consent was waived by the board
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records.
Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes, was evaluated.
Results for both recipient and donor ABO blood groups (ABO) and HLA.
Immunosuppressive therapy was determined, including induction therapy with basiliximab or anti-thymocyte globulin, and calcineurin inhibitors for maintenance therapy.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infection.
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
The secondary outcome was all-cause mortality, based on data obtained from the National.
All patients were followed until graft failure or March 2018.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were collected.
Protocol biopsies were performed at zero-time, on the 10th day and 1 year after transplantation, and every year thereafter.
Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
All pathologic findings were examined by a nephropathologist.
The development of de novo DSA, was defined as any newly developed anti-HLA class I or II antibody Statistical analysis
All statistical analyses were performed using Stata software. .
Categorical variables were compared using χ2 and Fisher’s exact tests and continuous variables were compared using Student’s t-test.
Risk factors for PCP occurrence were analyzed using univariable and multivariable Cox proportional hazard models.
Propensity score matching was performed to account for the imbalance in baseline characteristics between the PCP-positive and -negative groups.
Scores were created with matching variables including age, gender, donor type, type of pre-transplant dialysis, hypertension, the usage of prophylactic antibiotics, and CMV positivity which had P values under 0.1 in multivariable Cox analysis for the risk of PCP.
Graft survival, overall patient survival, risk of rejection and development of DSA were analyzed using univariable and multivariable Cox proportional hazard models.
A P value < 0.05 was considered to indicate statistical significance Baseline characteristics and risk factors of PCP
The median duration of follow-up was 6.2 years.
Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Discussion
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured [17, 18].
The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
Previous studies have shown that CMV infection increases a risk of PCP [20–22], as supported by the present results.
This may be because CMV might modify the host immune response, leading to immune suppression [23, 24].
T-cells, especially CD4 T cell, are important factors affecting the vulnerability to and resolution of PCP [26], and alteration of the T cell response by CMV might aggravate pulmonary impairment during PCP activation [27]. Findings
Occurrence of PCP was significantly associated with overall graft failure Outcome univariable multivariable
Interstitial fibrosis and tubular atrophy 1.51 (0.72–3.15) 0.274 1.62 (0.77–3.41) 0.204.
PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Considering both the significant effect of PCP on mortality and the negative effect on graft outcome over long-term period, prophylaxis against.
The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
The duration of antibiotic prophylaxis might differ between centers, which could alter the risk of PCP or other transplant outcomes.
This did not hinder the study purpose on the relationship between PCP and transplant outcomes. Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
Kim et al BMC Nephrology (2019) 20:212 Page 6 of 8 both the risks of mortality and graft failure.
Robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients
Background: Infection is the 2nd most common cause of death in post-kidney transplant recipients after cardiovascular causes. PCP can occur up to 14% in PKT without prophylaxis with mortality up to 50 % despite aggressive AB treatment. methods: This is a retrospective observational study that analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. Graft & survival outcomes were compared between PCP-positive & negative PKT groups. PCP was defined as radiological findings by CT plus PCR positivity or direct immunofluorescence of sputum or BAL fluid. Prophylactic use of AB was defined as TMP/SUL > 4 weeks during the 1st month after kidney transplantation. results: 4.5 % of patients develop PCP. Risk factors were lack of initial prophylactic AB prescription & CMV positivity. The positivity of PCP showed a hazardous ratio of graft failure & mortality in comparison to the negative PCP group but no evidence of subsequent de-novo DSA or pathological evidence of t-cell mediated rejection, Ab-mediated rejection, or IFTA. conclusion: The risk of PCP in PKT increased with male gender, CMV positivity & non-use of prophylactic Antibiotic PCP infection increases risks of mortality & graft failure independent of increased risk of rejections. The use of prophylactic antibiotics & aggressive treatment of PCP is strongly recommended. – Level of evidence: Level III, retrospective observational study
Introduction
o The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis (mortality up to 50%)
o The relationship between PCP and mortality was investigated by several studies, but the effect of PCP on graft rejection and overall graft outcomes not well explored
Aim of the study: address the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Methods
o Include total of 1502 kidney transplant patients at Seoul National University Hospital from (2000-2017) (Patients > 18 years and only kidney transplantation)
o The graft and survival outcomes were compared between PCP-negative and PCP-positive groups
o The primary outcome was death-censored graft failure (return to dialysis or kidney retransplantation)
o The secondary outcome was all-cause mortality
Results
o The median duration of follow-up was 6.2 years
o Of the 1502 patients, 68 (4.5%) developed PCP after kidney transplantation (median time was 5.2months and 79.4% of cases developed during the first year after transplantation)
o Positive CMV and the non-use of oral prophylactic antibiotics were risk factors of post-transplant PCP
o Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure (All patients were male with no history of prophylactic antibiotics after transplantation)
o During follow-up, 11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and-negative groups, respectively (All-cause mortality was higher in the PCP-positive group than in the PCP-negative group)
o The most common cause of death was acute respiratory distress syndrome related with PCP.
o The PCP-positive group had higher rates of graft failure and mortality than the PCP-negative group (the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy)
Discussion
o This study demonstrated that male gender and CMV positivity were risk factors for PCP and the use of oral prophylactic antibiotics prevent the risk of PCP
o The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs
o Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
Limitations of the study:
1. A retrospective study
2. Duration of prophylactic antibiotics was 1month, which was shorter than the guideline recommendation (i.e., 3–6months), which might increase overall risk of PCP in study subjects
3. The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP
Conclusions
o Risk of PCP include male gender, positivity for CMV, and non-use of oral prophylactic antibiotics
o PCP is a risk factor of both mortality and long-term graft failure, , irrespective of rejection
o Appropriate prophylaxis may be needed to prevent PCP and subsequent graft failure
What is the level of evidence provided by this article?
A retrospective observational study (level III)
Impact of Pneumocystis jirovecii pneumonia on Kidney transplant outcome: Background Death-related graft failure had been dramatically improved as a result of improving immunosuppressant protocols, more studies and observation are needed to reduce death-unrelated graft failure, to improve the total causes of mortality (opportunistic infection). Infection is an important second factor of death in functioning graft recipients, following cardiovascular disease. Pneumocystis jirovercii is an opportunistic infection in an immunocompromised recipient with an incidence of 0.6 to 14% among kidney transplant recipients and mortality of up to 50% although aggressive antibiotic therapy. This Article assesses the effect of PCP on kidney transplant outcomes, including graft failure and rejection. Discussion
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, with an unclear life cycle as it can not be cultured.
Male gender and CMV infection were associated with PCP, and the risk are reduce with the use of antibiotic.
PCP is an independent risk factors long-term graft failure and overall mortality, so intense treatment and prophylaxis is recommended post-transplantation.
The association between PCP and MCV is that; the MCV infection affect the T cell function and accerelate aging, so it modify the host immunity, and affect the resolution of PCP, and the PCP can lead to pulmonary failure.
Pre-transplant dialysis are shown to be a protective against PCP.
Uremic syndrome is noticed ti be an another risk factor of PCP.
PCP by this study did not associated with any rejection episodes, however, certain infection associated with AKI and 50% of cases did not resolve completely.
KDIGO recommend that all recipients receive prophylaxis against PCP for 3-6 months after transplantation, however the dose and the duration of treatment still now not established.
Limitation of the study
The study was a retrospective.
The duration of the prophylaxis was for 1 month, while the recommendation is from 3-6 months, which may increase the overall risk of PCP.
The study did not established the underline mechanism and the risk of subsequent effect of PCP.
Conclusion
Risk of PCP were aggravated with;
Male gender.
CMV +.
Non-use of recommended prophylaxis.
PCP increase the risk of mortality and graft failure.
Accordingly prophylaxis against PCP are needed and to prevent graft failure.
The present study will be the basis of the future clinical trials on the use of prophylaxis in the kidney transplant recipients.
Level of evidence Level ((III)), retrospective study
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Introduction
· Infection is the second most common cause of death after CVD in patients with functioning grafts.
· The incidence of P. jirovecii pneumonia (PCP) is 0.6 to 14% among kidney transplant recipients without prophylaxis.
· Mortality related to PCP is up to 50% despite aggressive antibiotic therapy.
· The effect of PCP on graft rejection and overall graft outcomes has been less-well studied. Methods
· This retrospective observational study.
· Included 1502 patients who had kidney transplantation without pancreatic transplantation and above 18 years of age at Seoul National University Hospital from January 2000 to December 2017.
· PCP was defined as the presence of findings suspicious of PCP on chest CT plus PCP positivity on PCR or direct IF stain of sputum or BAL fluid.
· CMV positivity was defined as >20 copies/ml on PCR or positive viral culture.
· The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
· The secondary outcome was all-cause mortality.
Results
· 4.5% experienced PCP after kidney transplantation
· CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
· There was a significant relationship between PCP and graft failure, with HRs of 3.34 and 3.33 respectively.
· PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 P=0.027).
· All the patients who developed graft failure were male and had no history of prophylactic antibiotics usage after transplantation.
· All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
· The PCP-positive group had a significant higher risk of mortality adjusted HR, 10.99.
· Nine of Eleven patients died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion
· The clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
· The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP.
· The use of oral prophylactic antibiotics seemed to prevent the risk of PCP
· PCP increased the risk of long-term graft failure; however, this was not related to rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
· As, PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
· In this study pre-transplant dialysis was identified as a protective factor of PCP, resolution of uremia would decrease the risk of PCP. Further studies are needed in the aspect.
· PCP itself did not affect the risk of acute rejection and de novo DSA production. The occurrence of PCP was significantly associated with overall graft failure probably due to non-immunological factors such as the production of proinflammatory cytokines.
· Mortality risk was elevated in patients with PCP in the first 3 months after diagnosis of PCP infection. The cause of death was either PCP itself or the other infection superimposed on PCP.
Conclusion
· PCP significantly increases both the risks of mortality and graft failure. Accordingly, vigorous prophylaxis may be needed. 2. The level of evidence is 3
1-Please summarise this article. Introduction;
-Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
-Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured.
-The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy. Methodology;
-Thisstudy included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
-After excluded (325 patients; the remaining 1502 patients were finally included and their data were reviewed.
–Exclusion criteria; Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded.
-After a propensity score matching was performed,the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. Results; –The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
-There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
-After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
-Although the acute T cell-mediated and antibody-mediated rejection episodes or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted.
-The PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients .
-Mortality risk was elevated in patients with PCP. Nine out of eleven (81.8%) patients died within 3 months after diagnosis of PCP infection.
-The causes of death in these patients were either PCP itself or the other infection superimposed on PCP.
-During the follow-up period, 11 patients (16.2%) died in the PCP-positive and 13 patients (11.0%) died in PCP-negative groups.
-The 28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%).
-The PCP-positive group had a higher risk of mortality than the PCP-negative group.
-The most common cause of death was acute respiratory distress syndrome related with PCP.
-CMV infection increases a risk of PCP , as supported by the present results.
-This may be because CMV might modify the host immune response, leading to immune suppression.
-CMV infection affects the T cell compartment and accelerates aging of T cells; especially CD4 T cells which are important factors affecting the vulnerability to and resolution of PCP.
-Alteration of the T cell response by CMV might aggravate pulmonary impairment during PCP activation.
Conclusions;
-Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes ,have not been fully evaluated.
-The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
-Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
-According to the KDIGO, it is recommended that all recipients receive prophylaxis against PCP for 3–6 months after transplantation.
-Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
Limitation;
-Although this study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes. –It was a retrospective study, making it difficult to demonstrate cause and effect definitively.
-The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (3–6 months), which might increase overall risk of PCP in study subjects.
-However, definitive guidelines on the duration and dosage of PCP prophylaxis are not available and more research is needed to determine the appropriate approach.
-The duration of antibiotic prophylaxis (more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes.
-The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
2-What is the level of evidence provided by this article? Retrospective observation study
This retrospective observational study; Level of evidence III
Impact Of Pneumocystis Jirovecii Pneumonia on Kidney Transplant Outcome 1. Please summarise this article. Introduction: Infection is a significant risk factor for mortality in kidney recipients and it is following cardiovascular disease (CVD) in order as the second most common cause of death with a functioning graft. Pneumocystis jirovecii (PJP), previously known as pneumocystis carinii (PCP) is one of the opportunistic infections that causes serious pneumonia in immune compromised patients.
P. jirovecii pneumonia (PJP) occurs in 0.6 to 14% of kidney transplant patients without prophylaxis, with a 50% mortality rate despite rigorous antibiotic treatment. PCP has been linked to mortality, but its impact on graft rejection and outcomes has been less studied.
The impact of PJP on allograft rejection and outcomes is unknown.
Aim of the study:
Aim to Evaluate of PCP infection impact on kidney graft outcome including failure and rejection. Method of study :
Retrospective observational study
Number of subjects: 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017, after excluding those under 18 years old or who received simultaneous kidney-pancreas or kidney-liver transplants.
PC pneumonia (PCP) diagnosis: Suspicious findings on a chest CT combined with microbiological confirmation (PCR or IF staining of PC on sputum or bronchio-alveolar lavage)
Immunosuppressive therapy was determined, including induction therapy with basiliximab or antithymocyte globulin, and calcineurin inhibitors for maintenance therapy.
Initial use of oral prophylactic antibiotics was defined as a prescription of trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture.
Data on biopsy-proven rejection, antibody mediated rejection, and interstitial fibrosis and tubular atrophy were collected.
The primary outcome:
Death-Censored Graft Failure
The secondary outcome: all-cause mortality. Statistical analysis:
Statistical analysis was performed using Stata software (version 15.1, StataCorp, College Station, TX, USA).
Data were expressed as mean ± standard deviation for continuous variables or counts with percentages for cat-egorical variables.
Risk factors for PCP occurrence were analyzed using univariable and multivariable Cox proportional hazard models, and graft survival, overall patient survival, risk of rejection and development of DSA were analyzed using Kaplan–Meier methods.
A P value < 0.05 was considered to indicate statistical significance.
Results:
The median duration of follow-up was 6.2 years, 68 (4.5%) experienced PCP after kidney transplantation, and 79.4% developed during the first year after transplantation.
CMV positivity and non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
About 4.5% diagnosed with PCP.
Important risk factors by multivariate analysis.
1) CMV +ve patients 2) Absence of prophylaxis 3) male gender.
Allograft failure and mortality are more common in PCP positive group compared to PCP negative group.
No clear association between PCP and development of de novo DSA, or acute/chronic rejection.
PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients, with HRs of 3.34 (1.31–8.56) and 3.33 (1.30–8.53) respectively.
To determine the cause of the elevated risk of graft failure, we evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs.
PCP-positive patients with graft failure had a high risk of rejection, interstitial fibrosis, tubular atrophy, and de novo DSAs, suggesting that different graft failure rates may be related to nonimmunological factors such as acute kidney injury.
The PCP positive group had a higher risk of mortality than the PCP negative group, with the most common cause of death being acute respiratory distress syndrome.
Discussion:
This study found that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of long-term graft failure.
Intensive treatment and prophylaxis is recommended after transplantation.
CMV infection increases the risk of PCP, and pretransplant dialysis is a pro-tective factor.
Uremic condition is linked to altered immunological response.
PCP itself did not affect the risk of posttransplant rejection and de novo DSA production but was significantly associated with overall graft failure.
Viral infections such as CMV, BK virus, and hepatitis C virus, and certain bacter-ial infections such as Pseudomonas aeruginosa, can affect allograft dysfunction by modulating non-immunological factors such as hemodynamic change and pro-inflammatory cytokines.
Mortality risk was elevated in patients with PCP infection, with 81.8% dying within 3 months.
Prophylaxis against PCP is recommended for 3-6 months after transplantation, but definitive guidelines on the duration and dosage of prophylaxis are not available.
This study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
However, the present observational study design could not determine the mechanisms underlying the risk and sub-sequent effect of PJP.
Limitations:
Retrospective observational study
Prophylactic antibiotic was used for one month, as opposed to current KDIGO recommendation of 3 to 6 months.
Conclusion: Prophylaxis is needed to prevent PJP and graft failure in kidney transplant recipients. Adequate duration of prophylactic antibiotic reduces the risk of PJP infection in solid organ transplantation and its consequent effect on graft failure/mortality.
More RCTs needed to give us information about PJP prophylaxis in kidney recipient patients. 2. What is the level of evidence provided by this article? Level of evidence III, Retrospective observation study
– Infection is considered the second most common cause of death in renal replant recipient s after cardiovascular disease
– Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that cause severe lung injury, and is associated with increased morbidity and mortality in renal transplantation
– The Incidence varies between 0.6-14% , and once occur around half of the cases die despite treatment
– This is a retrospective study evaluating 1502 renal transplant recipients at single center between 2000 and 2017 and asses the following :
Incidence of PCP infection
Graft and patient survival in PCP positive cases compared to PCP negative cases
Risk factors for development of PCP infection
Results:
4.5 % of renal transplant recipient in the current study develop PCP (68 patients)
Mortality rate is 11 times higher in PCP group compared to PCP negative group, around 80 % of cases died within 3 months of diagnosis.
Graft survival is 3 times lower in PCP positive group compared to PCP negative group, but is not related to the development of DSA, TCMR, ABMR or tubular atrophy. It is not known if graft dysfunction occur due to the infection itself or the induction of chronic inflammatory condition that cause graft failure.
Risk factors for PCP infection include male gender, the un-use of initial prophylaxis and CMV infection. CMV infection was found by other studies to accelerate aging of T cells (especially CD4 T cells)
Conclusions:
PCP is associated with lower patients and graft survival, irrespective of rejection.
PCP is more common in patients who did not receive prophylaxis, so prophylaxis is advised to prevent long term adverse outcome.
What is the level of evidence provided by this article?
It is a retrospective study, level of evidence III
Summary Introduction
Infections are the second most common cause of death in kidney transplant recipients with a functioning graft.
PCP is an opportunistic infection that causes a pulmonary infection in immunocompromised persons.
Incidence rate of PCP varies between 0.6-14% in kidney transplant recipients without prophylaxis, and its mortality can go up to 50%. Aim of this study:
To determine the impact of PCP on kidney transplants outcomes including graft failure and rejection. Methodology:
This was a retrospective observational study in Seoul. Carried out between January 2017 and December 2017.
They included 1502 participants. Exclusion criteria:
Patients under 18 years
Patients with simultaneous kidney- pancreas or kidney-liver transplants.
They were followed till March 2018 or they developed graft failure whichever occurred earlier.
PCP was diagnosed by the presence of finding suspicious for PCP by a radiologist on CT chest plus PCR positivity or direct immunofluorescence stain of sputum or BAL.
CMV positivity was diagnosed as >20 copies/ml. Primary outcome: death censored graft failure Secondary outcome: All cause mortality. Results:
68 participants (4.5%) developed PCP. Median time to infection was 5.2 months.
79.4% of the infections occurred in the first year post transplant.
Median time of followup was 6.2 years.
Of the 68, 9 had death censored graft failureand died within 3 months after occurrence of the PCP, cause of the death was ARDS secondary to PCP.
The nine patients were all males and were not on antibiotic prophylaxis.
Of the 68, 28 had concurrent other infections and 8 of them died.
11 (16.2%) and 13(11%) patients in the PCP positive and negative group died.
All cause mortality was higher in the PCP positive group.
Eight out of the nine patients with death censored graft failure had acute kidney injury. Discussion:
Life cycle of PCP is unknown because it can’t be consistently cultured.
Male gender and CMV positivity were risk factors associated with PCP.
Oral prophylactic antibiotics seem to prevent the risk.
PCP increased the risk of long term graft failure.
This study supports previous studies results that CMV infection increases risk of PCP infection.
Pre-transplant dialysis was associated as protective factor, could be due to clearing the uraemia state that is associated with altered immunological response.
PCP infection didn’t increase the risk of rejection suggesting non-immunological factors may be associated.
Mortality was high in the PCP positive group caused of death was either the PCP itself or there infections superimposed on the PCP.
Thus prophylaxis is strongly recommended. Limitations:
It was a retrospective study thus can’t demonstrate cause and effect definitively.
Patients were only on prophylaxis for 1 month which is shorter than guideline recommendation. KDIGO recommends 3-6 months. This might have increased overall risk of PCP in the participants.
Being an observational study they couldn’t determine the mechanism underlying the risk and subsequent outcomes.
Strengths:
It was able to demonstrate relationship between PCP and outcome. Conclusion:
Risk for PCP is high in kidney transplant recipients who were male, had CMV positivity and were not on antibiotic prophylaxis. PCP increases risk of mortality and graft failure. Hence prophylaxis required to prevent PCP and subsequent graft failure. Level of evidence: 3
Please summarise this article.This is a retrospective observational study from a single center in the south Korean population with a follow-up period of 17 years, data were collected from electronic medical records in the period between 2000-2017, and the aim of this study was to determine the impact of PCP infection on the overall graft and patient survival, and the immunological impact on rejection Study design and methods
A retrospective observational study from a national university single center included 1502 kidney transplant recipients from 2000-2017 after the exclusion of those under the age of 18 years or those with dual transplantation ( kidney & liver or kidney &pancreas ), the patient’s clinical characteristics and demographic were taken from electronic medical records in addition to the ABO compatibility, HLA typing, and Mismatches, induction type basiliximab Vs ATG and maintenance immunosuppression types ( the use of triple maintenance immunosuppression including steroid, MMF, and CNI ), re transplantation, They use the definition of PCP as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid. They use cotrimoxazole as prophylaxis from the first 4 weeks following kidney transplantation, they don’t have to use pentamidine or atovaquone as alternative prophylaxis. they defined CMV positivity as > 20 copies/ml on polymerase chain reaction or a positive result on viral culture.
They screen for graft rejection by protocol biopsies starting from day 0, pre-transplantation then annual protocol biopsy or whenever indicated, also DSA monitoring for denovo DSA for both class1, 11 The primary outcome of this study was death-censored graft failure (return to dialysis or kidney re-transplantation). The secondary outcome includes all-cause mortality outcome and impact on graft survival including rejection and graft failure. Results
Table 1 shows the total patients’ clinical characteristics and demographics, median FU of 6.2 years, from a total of 1502 patients only 68 ( 4.5%) got PCP with an infection rate of 6.8 cases/1000 persons /year with medium-time for PCP infection around 5.2 months .majority of PCP infection occur after 1 year of transplantation in 79% of cases, more in male recipients, also PCP prevalence was more in ABO Incompatible and those underwent desensitization, induction type of IS and CMV co-infection, After modification for many covariates, only CMV positivity and the non-use of oral prophylactic antibiotics was associated with an increased risk of PCP. PCP infection and graft outcome
Between 68 PCP-positive recipients, 9 (13.2%) patients established death-censored graft failure. the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients
(Adjusted HR, 3.06 [1.14–8.26]); P = 0.027)
Higher rate of graft failure in PCP-positive recipients and it’s due to non-immunological factors such as concurrent acute kidney injury.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group. The most common cause of death was acute respiratory distress syndrome related to PCP within the first 3 months of infection. No difference in the rate of acute TCM, AMR, or denovo DSA between the two groups.
Discussion
The results of this study confirmed that male gender and =infection with CMV plus non-use of antibiotics prophylaxis are major risks for PJP after kidney transplantation infection can impact the graft and patient survival and was not through the rejection episodes or IFTA or denovo DSA, and the aggressive treatment and antibiotics prophylaxis is mandatory after kidney transplantation.
Previous studies supported the finding of this study in regards to CMV co-infection and the risk of PCP as CMV can affect the T cell immune response like CD4, this alteration in T cell response by CMV might aggravate
pulmonary impairment during PCP activation.
Conclusion:
this observational study confirms that male gender and CMV – co-infection with non-use of prophylaxis AB as major risks factors for PCP after transplantation also PCP infection can impact both graft and patient survival mainly through non-immunological effects, we need more future studies to address the best timing and duration of AB prophylaxis after transplantation
Limitations of the study
1. Retrospective design
2. The definition of AB prophylaxis within 4 weeks? Which is shorter than the duration recommended by the KDIGO guideline ( 3-6 months ).
3. The current observational study design could not determine the mechanisms underlying the risk and sub[1]sequent effect of PCP.
2. What is the level of evidence provided by this article?
The Aim of the Study ;
To evaluate the impact of PCP on kidney transplant outcomes, including graft failure and
rejection.
The Type of the Study ;
This retrospective observational study.
Ethical Approval ;
Was approved by the institutional review board of Seoul National University Hospital and complied with the Declaration of Helsinki.
The Population ;
1502 kidney transplant recepients.
The Exclusion Criteria ;
1-Patients who were under 18 years old .
2- Patients who received simultaneous kidney–pancreas or kidney–liver transplants .
The Method;
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
The Result of the Study ;
1- The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
2-The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group.
3-The PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings ,such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
The Limitations of the Study ;
1-It was a retrospective study, making it difficult to demonstrate cause and effect definitively.
2-The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Conclusion;
1-The results of this study demonstrated that male gender and CMV positivity were risk factors associated with PCP.
2-The result of this study demonstrated that ,the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
2-The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
3-The results of study demonstrated that , PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
4-Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
5-The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
What is the level of evidence provided by this article?
Level III
1- Summary: Objectives:To evaluate the impact of PCP onkidney transplant outcomes, including graft failure andrejection. Material and methods:
A retrospective study.
Included all adult renal transplantation between 2000 and 2017
Patients were stratified according to diagnosis of PCP (PCP positive and PCP negative).
The primary outcome was death-censored graft failure
The secondary outcome was all cause mortality.
Results:
The study included 1502 patients
68 (4.5%) experienced PCP. The median (IQR) time to the development of PCP was 5.2 (3.9-10) months .
Multivariate analysis showed that male gender (P=0.007), CMV positivity (P<0.001) and lack of initial oral antibiotic prophylaxis (p= 0.016) were risk factors of post-transplant PCP. Where hemodialysis was a protective factor.
After propensity score matching to mitigate the difference in baseline data, 118 PCP-negative patients were compared to 68 PCP-positive
Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure which is statistically significant higher than PCP-negative group (P=0.008)
The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P =0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group.
The PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusion: PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
Immunosuppressive medications have reduced death-censored graft failures but have not affected mortality rates.
Although there is limited information on the immunologic outcomes of kidney transplant patients, inflammation is a significant risk factor. To increase the success rates of survival, further research is required.
An opportunistic pathogen called Pneumocystis Jirovecii pneumonia (PCP) causes severe lung infection in immunocompromised hosts, with a death rate of up to 50%.
Method
The 1502 adult patients who received kidney transplants at Seoul National University Hospital between 2000 and 2017 were the subject of this retrospective observational study.
The graft and survival results between the PCP-negative and PCP-positive groups were examined after the propensity score matching procedure.
Results
Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure.
PCP-positive recipients had a higher risk of death-censored graft failure than PCP-negative recipients.
All the patients were male and had no history of prophylactic antibiotics usage after transplantation.
PCP increased the risk of graft failure but did not differ between PCP-positive and negative groups.
Graft failure rates may be related to non-immunological factors such as acute kidney injury.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group (F).
The PCP-positive group had a higher risk ofmortality.
The most common cause of death was acute respiratory distress syndrome related to PCP.
Discussion
The life cycle of the ascomycetous fungus Pneumocystis Jirovecii, which causes opportunistic infections, remains unclear.
Unknown is PCP’s potential impact on allografts over time.
While PCP is typical following kidney transplantation, its clinical ramifications have not yet been thoroughly examined.
Oral prophylactic antibiotic treatment is advised in cases where a person is male and CMV-positive.
Immune suppression and pulmonary impairment can result from an increased CMV infection because it alters the host’s immune response.
Pre-transplant dialysis helps to preserve PCP. A protracted pre-transplant dialysis regimen, however, harms the host immune system.
Hemodynamic changes and other non-immunological variables, such as PCP, were linked to transplant failure.
Because PCP did not raise the likelihood of rejection following infection, non-immunological variables could be at blame.
Proinflammatory cytokines, which are upregulated in PCP-positive individuals, may cause non-immunological graft damage.
During three to six months following transplantation, PCP prophylaxis is advised, although clear recommendations are required.
Because of PCP’s major impact on mortality and graft outcome, prophylaxis against it is highly advised.
Limitations:
It was a retrospective study, making it difficult to demonstrate cause and effect definitively
The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months),
The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion:
PCP is increased in kidney transplant cases with male gender, positivity for CMV, and non-use of antibiotics.
Prophylaxis is needed to prevent PCP and graft failure in kidney transplant recipients
============================================
What is the level of evidence provided by this article?
Pneumocystis jiroveci pneumonia (PCP) is a leading cause of morbidity & mortality in kidney transplant recipients & it continues to be a problem. A lack of data exists on PCP’s effects on the long-term success of grafts, despite the fact that the acute phase toxicity in patients with PCP is well understood.
The study
In this retrospective observational study, 1502 adult patients who received KTXs at Seoul National University Hospital between 2000 & 2017 were examined.
The results of the graft and survival were compared between the PCP-negative and PCP-positive groups after propensity score matching was completed.
The primary outcome:
Death-censored graft failure defined as a return to dialysis or kidney re-transplantation.
The secondary outcome:
All-cause mortality, based on data obtained from the National Database of Statistics Korea.
Results Baseline characteristics & risk factor of PCP:
The median duration of follow-up: 6.2 years
Of the 1502 patients, 68 (4.5%) developed PCP after KTX.
The median time to the development of PCP: 5.2 months.
CMV positivity & the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
PCP & transplant outcomes:
9/68 (13.2%) of PCP-positive recipients developed death- censored transplant failure.
The PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients.
All the patients were male & had no history of prophylactic antibiotics usage after transplantation.
8/9 patients (88.9%) sustained AKI during the inpatient period, & 4 of them (50%) did never recover graft functions fully despite responding to PCP.
11 patients (16.2%) & 13 patients (11.0%) died in the PCP-positive &-negative groups, respectively.
The 28 PCP-positive patients had concurrent other infectious diseases, & 8 patients died (28.6%).
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group.
The PCP-positive group had a higher risk of mortality than the PCP-negative group.
9/11 patients (81.8%) died within 3 months after the occurrence of PCP. The most common cause of death was ARDS related with PCP.
Discussion
The study found that oral prophylactic antibiotic use appeared to reduce the risk of PCP and that male gender and CMV positive were risk variables linked with PCP. Long-term graft failure was more likely when PCP was present, although this connection was independent of rejection, interstitial fibrosis, tubular atrophy, or de novo DSAs.
After TX, intensive care & prophylaxis are recommended due to PCP’s link to both graft failure & overall mortality.
The current findings are consistent with other research that suggests CMV infection raises PCP risk. This might be due to the possibility that CMV modifies the host immunological response, causing immune suppression.
Pre-transplant dialysis was identified as a protective factor of PCP. This factor has not been reported for in any previous studies.The underlying processes of the aforementioned association must be determined by additional research.
The presence of PCP was strongly linked to total transplant failure. As previously shown, many viruses (CMV, BKV, & HCV) & bacterial infections like Pseudomonas aeruginosa also affect allograft failure by altering non-immunological factors including hemodynamic change.
PCP did not raise the risk of any rejection following infection in the trial, indicating that non-immunological factors may have contributed to the data.
Patients with PCP had a higher risk of mortality. Within 3 months of diagnosed of PCP infection, 9/11 (81.8%) patients died. PCP itself or the other infection that coexisted with PCP were the reasons of death.
Prophylaxis against PCP is highly advised given its large impacts on mortality & graft outcome over a long period of time.
KDIGO recommended prophylaxis against PCP for 3-6 months following TX for all recipients. Unfortunately, there are no clear recommendations on the length of time or dosage for PCP prophylaxis, thus more study is required to establish the best course of action.
Limitations
The study achieved its primary purpose by examining the relationship between PCP & TX outcomes. However, it is a retrospective study, making it difficult to demonstrate cause & effect definitively.
The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
The study design could not determine the mechanisms underlying the risk & subsequent effect of PCP.
========================= 2. What is the level of evidence provided by this article?
A case-control study attempts to identify potential exposure factors following a known disease incidence, whereas a retrospective cohort study compares the risk of getting a disease to some already known exposure factors.
Infections is the second most common causing of death in KTX with functioning graft
pneumocystis jirovecii is an opportunistic ascomycetous fungus that causes infection in immunocompromised patients ,leading to severe pulmonary infection (pneumocystis pneumonia /PCP)
PCP associated with graft dysfunction and mortality among TKX patients, so required intensive treatment and prophylaxis program.
this microorganism can not be cultured
the effect of graft dysfunction property is via non-immunological pathways, causing pro-inflammatory cytokine releasing such as interleukin 1,6,& 8 that causes acute kidney damage
CMV increases risk of PCP
KDIGO guideline recommended that all recipients receive 3-6 months prophylaxis
there is controversy about the exact duration and dosage of prophylaxis
risk factors for PCP : male gender, CMV positive, non-use of prophylaxis and certain immunosuppressant medications
Infection is an important factor in the risk of death in kidney transplant recipients, and the incidence of most infectious diseases has been maintained over the past 15 years.
Further studies are needed to characterize and improve survival outcomes.
Pneumocystis jirovecii pneu-monia (PCP) is an opportunistic pathogen that causes severe pulmonary infection in immunocom-promized hosts, with a mortality of up to 50% despite aggressive antibiotic therapy.
This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
This retrospective observational study included 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017, excluding those under 18 years old or who received simultaneous kidney-pancreas or kidney-liver transplants.
Data from kidney transplant recipients was collected from electronic medical records and demographic characteristics such as age, gender, height, weight, and body mass index were collected.
Pretransplant status, prior history of transplantation, type and duration of dialysis, history of diabetic nephropathy, and comorbidities such as hypertension and diabetes were evaluated.
Immunosuppressive therapy was determined, including induction therapy with basiliximab or antithymocyte globulin, and calcineurin inhibitors for maintenance therapy.
Initial use of oral prophylactic antibiotics was defined as a prescription of trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture.
Transplant outcomes
The primary outcome was death-censored graft failure, while the secondary outcome was all cause mortality.
Data on biopsy-proven rejection, antibody mediated rejection, and interstitial fibrosis and tubular atrophy were collected.
Statistical analysis
Statistical analysis was performed using Stata soft-ware (version 15.1, StataCorp, College Station, TX, USA).
Data were expressed as mean ± standard deviation for continuous variables or counts with percentages for cat-egorical variables.
Risk factors for PCP occurrence were analyzed using univariable and multivariable Cox proportional hazard models, and graft survival, overall patient survival, risk of rejection and development of DSA were analyzed using Kaplan–Meier methods.
A P value < 0.05 was considered to indicate stat-istical significance.
The median duration of followup was 6.2 years, 68 (4.5%) experienced PCP after kidney transplantation, and 79.4% developed during the first year after transplantation.
CMV positivity and non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
PCP and transplant outcomes
PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients, with HRs of 3.34 (1.31–8.56) and 3.33 (1.30–8.53) respectively.
To determine the cause of the elevated risk of graft failure, we evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs.
PCP-positive patients with graft failure had a high risk of rejection, interstitial fibrosis, tubular atrophy, and de novo DSAs, suggesting that different graft failure rates may be related to nonimmunological factors such as acute kidney injury.
The PCP positive group had a higher risk of mortality than the PCP negative group, with the most common cause of death being acute respiratory distress syndrome.
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle is unknown.
This study found that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of long term graft failure.
Intensive treatment and prophylaxis is recommended after transplantation.
CMV infection increases the risk of PCP, and pretransplant dialysis is a pro-tective factor.
Uremic condition is linked to altered immunological response.
PCP itself did not affect the risk of posttransplant rejection and de novo DSA production, but was significantly associated with overall graft failure.
Viral infections such as CMV, BK virus, and hepatitis C virus, and certain bacter-ial infections such as Pseudomonas aeruginosa, can affect allograft dysfunction by modulating nonimmunological factors such as hemodynamic change and proinflammatory cytokines.
Mortality risk was elevated in patients with PCP infection, with 81.8% dying within 3 months.
Prophylaxis against PCP is recommended for 3-6 months after transplantation, but definitive guidelines on the duration and dosage of prophylaxis are not available.
This study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
However, the present observational study design could not determine the mechanisms underlying the risk and sub-sequent effect of PCP.
Please summarise this articlePneumocystis jirovecii (PJ) is a notable cause of morbidity and mortality in solid organ transplant recipients. This study assessed the effect of PJ infection on kidney transplant outcomes.
Methods:
Retrospective observational study
Number of subjects:1502 kidney transplant recipients>18 years (after excluding combined transplant recipients)
Place of study: Seoul National University Hospital
Duration of study: 2000-2017
PC pneumonia (PCP) diagnosis: Suspicious findings on a chest CT combined with microbiological confirmation (PCR or IF staining of PC on sputum or bronchio-alveolar lavage)
Results:The PCP positive and negative groups were matched using propensity score matching.
Incidence of PCP
68(4.5%) of subjects developed PCP
Median time of development 5.2 months
Almost 80% developed in first year.
The following risk factors were associated with an increased risk of PCP.
Male gender
CMV positivity
Absence of oral prophylaxis post-transplant
PCP-positive recipients had a higher risk compared to PCP negative in terms of
Death censored graft failure (adjusted HR, 3.06 [1.14–8.26])
The association between parameters is highlighted but cause and effect cannot be established due to study design.
Prophylactic antibiotic was administered for one month, as opposed to current KDIGO recommendation of 3 to 6 months.
Conclusion:Adequate duration of prophylactic antibiotic reduces the risk of PC infection in solid organ transplantation and its consequent effect on graft failure/mortalityWhat is the level of evidence provided by this article?Case-Control retrospective study:Level 3b
Although Death-censored graft loss reduced after use of immunosuppression but mortality rate with functioning graft remain unchanged.
Infection is an important cause of death in kidney transplant recipients (second cause after CVD) with functioning graft.
PCP can cause sever pulmonary disease in immunocompromised patients.
PCP incidence in kidney transplant recipients with out prophylaxis ~0.6%-14%. & mortality rate can reach 50% even with aggressive treatment.
The relation between CMV infection & BKV infection & acute rejection is well known, but the relation between CPC & acute rejection is not clear.
Aim of the study:
Evaluation of PCP infection effect on kidney graft outcome including failure & rejection.
Methods:
Retrospective observational study.
1827 kidney transplant recipients included in this study, but patients aged <18years, or have dual transplant excluded, so final number of patients was 1502.
The study period Jan 2000-Dec 2017.
Induction therapy were basiliximab or ATG & maintenance triple therapy (CNI, MMF & steroids).
PCP defined as suspected radiological chest CT finding with PCP positive PCR or direct IF of sputum or broncho-alveolar lavage.
Prophylaxis as TMSM used for >4weeks during first post transplant month.
Primary outcome: death-censored graft loss (return to dialysis or re-transplantation)
Secondary outcome was all cause of mortality.
Protocol biopsy done at 0 day, 10th day, & 1 year post transplant then every year & additional for cause biopsy done when indicated.
Result & discussion:
Male gender & CMV infection are associated with increased risk of PCP infection & using of prophylaxis reduce this risk.
PCP infection increase risk of long term graft loss which is not dependent of rejection, interstitial fibrosis & tubular atrophy or de novo DSA (non immunological factors & increase production of IL-1,6 &8).
Post transplant prophylaxis & intensive treatment is recommended to reduce risk of graft loss & mortality.
Pre-transplant dialysis is a protective factor of PCP infection.
Mortality risk increased due to PCP it self or due to other infection superimposed PCP.
KDIGO guideline recommend to use PCP prophylaxis for 3-6 months post transplantation of all recipients.
Limitation of the study:
retrospective design
prophylaxis used only for 4 weeks ( guideline recommend 3-6 months).
Retrospective study when the researcher start the study at the time follow-up has already completed.
Case control study when the researcher select cases & control depending on presence or absence of outcome & loopback in time for disproportionate exposure.
Infection is a significant risk factor for mortality in kidney recipients and it is following cardiovascular disease (CVD) in order as the second most common cause of death with a functioning graft.
Unfortunately,there is a scarcity of information on immunologic outcomes of after specific infection in kidney recipient.
Pneumocystis jirovecii (PJP) previousely known as pneumocystis carinii (PCP) is one of the opportunistic infection that causes serious pneumonia in immune compromised patients.
Incidence is 0.6 to 14% in kidney recipients in absence of prophylaxis and mortality is more than 50% with treatment.
The impact of PJP on allograft rejection and outcomes is unknown.
Methodology
This was retrospective cohort conducted at Seoul National Hospital from January 2000 to December 2017.
Only adult kidney transplant recipient were included.
At the end 1502 kidney transplant recipients were involved in the final analysis.
They did propensity score matching , then compared the allograft survival outcomes among two cohorts; PCP negative versus PCP positive.
The data were analyzed with the aids of Stata soft ware (version 15.1, Stat Corp, College Station, TX, USA) and the risk factors were analyzed by univariable and multivariable Cox proportion hazard models.
Results
About 4.5% diagnosed with PCP.
Important risk factors by multivariate analysis ; 1)CMV +ve pt 2) Absence of prophylaxis, 3) male gender.
Allograft failure and mortality are more common in PCP positive group compared to PCP negative group.
No clear association between PCP and development of de novo DSA, or acute/chronic rejection.
Conclusion
CMV, lack of prophylaxis, & male sex are important risk factors for CMV.
Once PCP infection is established , the risk of allograft failure and mortality goes up.
Therefore, is essential to give prophylaxis against PCP & monitor for CMV
More studies may be needed based the facts to give information regarding PCP prophylaxis in kidney recipient patients.
What is the level of evidence provided by this article?
Retrospective, you back to the records or registry and inspect individuals by their exposure, and case-control can be retrospective or prospective and inspect individual by their outcome or disease status.
Summary : Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Introduction
This article is concerned with the effect of pneumocystis jirovecii pneumonia on long term graft outcome and mortality.
About the offending agent
Pneumocystis jirovecii is a fungus that causes opportunistic infections. The purpose of this article also goes toward identifying whether the long term effect of OCO on allograft is due only to infection, or combined with other reasons such as chronic inflammation. This is an area that warrants more research.
Outline of the study
This study demonstrates that PCP risk was increased in cases of positive CMV and with male patients. In contrast, the risk of PCP greatly reduced with oral use of prophylactic antibiotics. PCP can lead to long term graft damage and even failure. This is not found to be associated with rejection, interstitial fibrosis, tubular atrophy, or de novo DSAs.
Due to the intensity of the complications caused by PCP, aggressive post transplant prophylaxis and treatment is recommended.
Discussion
PCP has been linked to male gender and CMV infection. CMV increases PCP risk in both male and female patients, and this could be attributed to CMV modifying the host immune response, resulting in immune suppression. IT affects the T cells and speedens aging in these cells, weakening immune response of the host and making it difficult to prevent or resolve PCP in the patient. Lung impairment is a significant clinical feature.
Protective factors against PCP include prophylactic antibiotics and pre transplant dialysis. Since uremia is linked to altered immune response, dialysis could help with resolution of uremia to an acceptable level, thus decreasing the risk of post transplant PCP. It is worth it to note that long term dialysis prior to transplant can have an opposite effect on the immune system and thus PCP incidence. Frequency and dose of dialysis may play a role in the outcome.
In addition, incidence of PCP did not increase the risk of acute rejection or de novo DSA production.
Conclusion
KDIGO guidelines recommend that all kidney transplant recipients receive prophylaxis against PCP for a period of 3-6 months post transplant. Limitations of this study include retrospective nature of the study making is difficult to clearly demonstrate cause and effect. In addition, this study used a very short period of prophylactic antibiotics (1 month) in comparison with guideline recommendations, thus leaving the possibility of increased risk of PCP.
Robust prophylaxis may be necessary to prevent PCP and long term graft damage or failure in these patients.
Level of evidence
This is a retrospective observational study looking for risk factor with subject of interest, and thus level of evidence is 3.
Introduction
Pneumocystosis is an opportunistic disease that causes severe interstitial pneumonia with high mortality in patients who have undergone solid organ transplantation.
Materials and methods
A single-center retrospective observational study conducted at Seoul University Hospital between 2000 and 2017 compared groups with and without pneumocystosis, setting the level of evidence 3.
Protocol biopsies were performed on D+0, D+10, and D+365 of the Transplant. Additional biopsies were performed if necessary.
Objectives
Primary – Graft failure and loss
Secondary – Mortality related to all causes
Results
The medical follow-up time was six years and two months. 1502 patients were followed with 68 patients presenting with infection (4.5% and 6.8 cases per thousand patients). After five months is the average time to present infections with 79.4% of cases in the first year.
Risk factors were male gender, ABO incompatibility, desensitization, and CMV positivity.
Pneumocystosis has HR 3.34 for graft failure and 3.06 for graft loss.
All-cause mortality was higher in the Pneumocystosis positive group with HR 10.99 being the main cause of mortality respiratory failure triggered by Pneumocystosis itself.
Discussion
The presence of CMV infection and the use of anti-lymphocyte drugs increase the risk of pneumocystosis. Its occurrence does not affect the risk of acute rejection or de novo DSA production.
Limitations
Retrospective study, making cause and effect difficult. In that center, prophylaxis was only for one month, against most guidelines that suggest 3 to 6 months of prophylaxis.
Conclusion
Pneumocystosis has a high risk of loss of graft function and there is a need for prospective studies to define the adequate duration of post-transplantation prophylaxis.
Pneumocystis jirovecii produces severe lung infections in immunocompromised patients. P. jirovecii pneumonia (PCP) occurs in 0.6 to 14% of kidney transplant patients without prophylaxis, with a 50% mortality rate despite rigorous antibiotic treatment. PCP has been linked to mortality, but its impact on graft rejection and outcomes has been less studied.
Method:
This was a retrospective study that looked at 1502 adult patients who had kidney transplants at Seoul National University Hospital between the years 2000 and 2017. Following the completion of a propensity score matching procedure, a comparison of the graft and survival results between PCP-negative and PCP-positive groups was carried out.
Results:
68 transplant recipients (4.5%) developed PCP. Cytomegalovirus positivity and absence of oral antibiotic prophylaxis were risk variables for post-transplant PCP in the multivariable Cox analysis.
The PCP-positive group exhibited greater hazard ratios of graft failure (3.1 (1.14–8.26); P = 0.027) and death (11.0 (3.68–32.80); P < 0.001) than the PCP-negative group. However, PCP did not cause de novo donor-specific antibodies or pathologic features such as T-cell or antibody-mediated rejection, interstitial fibrosis, or tubular atrophy.
Conclusion:
A positive test for CMV, the absence of oral prophylactic antibiotics, and a male gender all contribute to an increased risk of post-transplantation pneumonia (PCP).
PCP is a risk factor for long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment are needed to avoid the adverse transplant outcomes of PCP.
it is possible that rigorous prophylaxis will be required to avoid PCP and the eventual failure of the transplant. The current findings will serve as the foundation for future clinical studies concerning the administration of prophylaxis to patients with kidney transplants.
Level of evidence III, Retrospective observation study
1-Background
Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic pathogen which can lead to severe pulmonary infection in immunocompromised cases . P. jirovecii pneumonia (PCP) incidence is 0.6 to 14% in renal transplant recipients without prophylaxis, mortality can reach up to 50% even with intensive antibiotic therapy.
Unlike the effect of CMV and BKV on graft rejection ,the effect of PCP on graft rejection is less evaluated . Aim
Access the impact of PCP on kidney transplant outcomes, including graft failure and rejection. Methods
This is a retrospective observational study involving 1502 renal transplant recipients at Seoul National University Hospital within 17 year .
Medical details were obtained from records and PCP was diagnosed through CT findings and PCR or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
Cases were considered CMV positive if > 20 copies/ml on PCR or positive result on viral culture.
The primary outcome was considered death-censored graft failure ,through dialysis or renal retransplantation and the secondary outcome was all-cause mortality.
Both outcomes were compared between PCP-negative and PCP-positive groups Results
4.5% of the cases experienced PCP post transplantation. The risk factors of post-transplant PCP were CMV positivity and lack of oral antibiotic prophylaxis . Graft failure and mortality were higher in the PCP-positive group than the PCP-negative group. Meanwhile PCP was not associated with DSA occurrence or pathologic findings,such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy. Discussion
Pneumocystis jirovecii is an ascomycetous fungus that leads to opportunistic infections,it’s mechanism of graft affection is not investigated nor it’s outcomes evaluated.
Risk factors for PCP included male gender, CMV positivity while oral prophylactic antibiotic and pretransplant dialysis by decreasing uremia seemed to lower the risk.
CMV infection impairs CD4 T cell response thereby rendering the patient vulnerable to pulmonary infection by PCP .
PCP increased graft failure risk apart from rejection ,tubular atrophy and DSA .
It was suggested that PCP affect the graft in a non immunological way by stimulating the production of proinflammatory cytokines.
Therefore treatment and prophylaxis are mandatory.
KDIGO recommended that prophylaxis against PCP must be given to renal transplant recipients for 3–6 months after transplantation.
Limitations were being a retrospective study, antibiotic prophylaxis was 1 month rendering cases more liable to PCP infection also prophylaxis duration varied between centers ,another aspect is that this study wasnot able to detect the mechanisms which increases the risk and subsequent effect of PCP.
Conclusion
PCP is a risk factor for graft failure on the long term and mortality, apart from rejection.
Prophylaxis and treatment is crucial to avoid PCP and it’s complications.
2-Level of evidence is 3 as it is a retrospective study
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome:
1- Infection account 20 % (second cause of death) of mortality in SOT after cardiovascular complications which account 40% and remains the first cause of death with functioning graft.
2- Pneumocystis jirovecii pneumonie PCP is an an ascomycetous fungus opportunistic organism has 0.6-1.4% incidence of infection in renal transplant recipient without use of prophylaxis, and its mortality reaches 50% even with aggressive treatment.
3- Long term graft failure in association with PCP is not known it is due to infection or due to associated chronic inflammatory process or other factors.
4- Male gender and CMV are important risk factors associated with PCP.
5- Long term prophylaxis of PCP is associated with decrease incidence.
6- Aggressive treatment of PCP post transplant is important as it may associated with rejection and risk of other infections like CMV.
7- CMV infection is important risk factor for PCP as CMV alter T cell immune response especially CD4 which is important in aggravation or suppression of PCP.
8- Pre-transplant dialysis or uremia alters the immune response and increase risk of PCP post transplant.
9- The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production.
10- Occurrence of PCP was significantly not associated with overall graft failure.
11- Infections may also induce allograft injury (non-immune mechanism) by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8, these proinflammatory cytokines are known to be upregulated in patients with PCP.
12- Mortality with PCP is high either due to PCP itself or other associated infections.
13- Prophylactic treatment of PCP is highly recommended for 6 months post transplant to avoid high risk of mortality.
Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic agent that causes severe pulmonary infection in immunocompromised individuals.
The incidence of PCP varies from 0.6 to 14 % in kidney transplant patients without prophylaxis and mortality reaches 50%.
Aim of study
To evaluate the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Patients and methods
Retrospective observational study studied 1502 adult kidney transplant recipients from Seoul National University Hospital in the period between 2000 to 2017 and compared the graft and survival outcomes between PCP positive and PCP negative groups
Results
A total of 68(4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for CMV and lack of initial antibiotic prophylaxis were risk factors for post transplant PCP
The PCP positive group had higher hazard ratios of graft failure and mortality than the PCP negative group
PCP event was not related to development of denovo DSA or pathological findings as T cell mediated rejection and interstitial fibrosis and tubular atrophy
Conclusion
PCP is a risk factor for long-term graft failure and mortality irrespective of rejection
Level of evidence III
Aretrospective study analyzed 1502 adult patients who had kidney transplantation at Seoul National University Hospital between 2000 and 2017.
Results:68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
Conclusions:PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
level of evidence:3
This is a retrospective observational study involved 1502 kidney recipients. The graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
68 patients developed PCP after transplantation. positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were the risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group. Limitations of the study are:
1- This was a retrospective study
2- antibiotics were given for 1 month
level of evidence 3
Background:
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients. While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome.
Method:
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
Results:
A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusion:
PCP is a risk factor of long-term graft failure and mortality.
Is large study with relatively long period of follow up, however it is retrospective, single center study in restricted ethnic group.
Level of evidence: 111
This is a retrospective analysis of level 3 evidence
This was a retrospective observational analysis of the effect of PCP infection on long term graft survival in kidney transplant recipients.
1502 patients were followed for median of 6.2 years. out of which 68 (4.5%) patients developed PCP.
Risk factors for PCP includes: CMV and non use of antibiotic prophylaxis .
Please summarise this article.
Population: 1502 adult patient post kidney transplantation, single centre, between 2000-2017
Intervention: Nil (Retrospective observational study)
Comparator: PCP negative vs PCP positive
Outcome:
This paper demonstrated that PCP is associated with poor graft and patient survival. However the PCP event was not associated with subsequent, TCMR, ABMR or IFTA
What is the level of evidence provided by this article?
Level III
Level 3 of evidence
who get kidney transplants, who test positive for CMV, and who do not take oral prophylactic antibiotics are at increased risk of developing PCP. PCP greatly raises the risks of graft failure and mortality. In light of this, strong prophylaxis may be required to stop PCP and eventual transplant failure. Future clinical trials on the use of prophylaxis in kidney transplant patients will be built on the outcomes of the current study.
This article discusses the impact of Pneumocystis jirovecii pneumonia (PCP) on kidney transplant outcomes. PCP is an opportunistic infection that affects immunocompromised individuals, such as kidney transplant recipients. The study included 1,502 patients who underwent kidney transplantation between 2000 and 2017. The researchers found that PCP occurred in 4.5% of the patients, with a median time of 5.2 months after transplantation. CMV positivity and the non-use of oral prophylactic antibiotics were identified as risk factors for PCP. The occurrence of PCP was associated with an increased risk of death-censored graft failure, indicating that PCP infection contributes to long-term graft failure. However, this relationship was not dependent on rejection or other immunological factors. The study also found that PCP was associated with higher overall mortality in kidney transplant recipients. The findings highlight the importance of intensive treatment and prophylaxis for PCP after kidney transplantation to improve graft outcomes and patient survival. Further research is needed to determine the appropriate duration and dosage of PCP prophylaxis.
level of evidence 3
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Its retrospective observational study published in BMC Nephrology 2019 Level 3 Evaluating the effect of PCP infection on kidney transplant outcomes including graft failure and rejection.
Introduction:
Infection is the second most common cause of death in patients post-kidney transplant after cardiovascular. PCP is a yeast-like fungus organism that can cause severe pulmonary infection in 0.6 to 14% of immunocompromised Patients and finally can cause death in up to 50%.
Method:
1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017 were included then divided according to PCP to PCP-negative and PCP-positive matched groups then graft and patient survival outcomes were compared between both groups
Results:
1. 68 (4.5%) experienced PCP post-KT.
The median time of PCP was 5.2 months and 79.4% of cases developed during the first year.
CMV positivity and the non-use of PCP prophylactic drugs were associated with an increased risk of PCP.
Death-censored graft failure was 13.2% of PCP-positive recipients
2. 88.9% of PCP-positive patients experienced acute kidney injury and 50% did not recover after recovery from PCP.
3. The PCP-positive group had higher hazard ratios of graft failure than the PCP-negative group.
Limitation of the study:
Retrospective study with limited data and no clear histopathological diagnosis of the cause of AKI associated with PCP.
Conclusion:
· Positivity for CMV, and non-use of oral prophylactic antibiotics is associated with increased risk of PCP.
· PCP is associated with higher risks of graft failure and death.
What is the level of evidence provided by this article?
Level (3)
Introduction:
Pneumocystis jirovecii is a pathogen that causes severe lung infection in individuals with compromised immune systems. Pneumocystis jirovecii pneumonia (PCP) is a significant concern in kidney transplant recipients, with mortality rates of up to 50% despite antibiotic treatment. However, the impact of PCP on graft rejection and overall transplant outcomes has not been extensively studied. This article aims to analyze the effects of PCP on kidney transplant recipients.
Methods:
This retrospective observational study analyzed data from 1,502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. The collected data included demographic information, pre-transplant status, immunosuppressive therapy, PCP diagnosis, and cytomegalovirus (CMV) positivity. Graft and survival outcomes were compared between PCP-negative and PCP-positive groups. The primary outcome was death-censored graft failure, and the secondary outcome was all-cause mortality. Biopsy results for acute T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), interstitial fibrosis and tubular atrophy (IFTA), and donor-specific antibodies (DSAs) were also recorded.
Results:
All the recipients were male and had no history of prophylaxis. The results showed that CMV positivity and lack of prophylaxis were associated with a higher risk of PCP infection. Approximately 14% of PCP-positive patients experienced graft failure, and there was higher mortality at a median follow-up of 6.2 years, with an infection rate of 6.8 cases per 1000 person-years.
Discussion and Conclusion:
The study found that male gender and CMV positivity were associated with a higher risk of developing PCP, while the oral use of antibiotics was associated with a decreased risk. PCP infection was found to increase the risk of mortality and biopsy-proven graft loss due to AMR, TCMR, and IFTA. Therefore, prophylaxis is recommended to prevent PCP and reduce the risk of graft failure.
Level of Evidence:
This article provides Level III evidence.
Backgrounds: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in kidney transplant recipients. While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome.
Method: This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
Results: A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusions: PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
Level of Evidence-3
Summary of article-This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Graft and survival outcomes were compared between PCP-negative and PCP-positive groups.The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality.
Results-Of the 1502 patients,68(4.5%) experienced PCP after kidney transplantation.79.4 % of cases developed during the first year after transplantation .Among 68 PCP positive receipt ,9 (13.2%) developed graft failure.Although all variable were adjusted, in this study ,PCP positive recipient had a higher risk of death censored Graft failure ,than PCP Negative recipient .All cause mortality was higher in PCP positive group than PCP negative group.
The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP. The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs. Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
Level of Evidence-3
Summary:
Introduction
This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients.
Discussion
The given article is based on a retrospective observational study which analyzed kidney transplant recipients in Seoul between the years of 2000 and 2017.
Out of the total participants of the base study, 68 developed PCP post transplant. Risk factors were found to be CMV positivity and lack of initial antibiotic prophylaxis.
About the causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in immunocompromised people. It can affect kidney transplant recipients who do not have prophylaxis and can cause fatalities in upto 50% of those affected even with aggressive antibiotic cover.
This fungi cannot be consistently cultured, and thus its life cycle is not known.
One of the major risk factors includes CMV infection. This is because CMV can modify host immune response, thus leading to suppression of the immune system. The pathogen accelerates aging of host T cells, thus increasing vulnerability to PCP and decreasing rate of infection resolution. This is also why co-infection can worsen pulmonary impairment.
Antibiotic cover and pre transplant dialysis are protective factors against PCP. Pre transplant resolution of uremia lowers the risk of PCP in the post transplant period.
Adequate prophylaxis needs to be for a period of 3-6 months post transplantation.
Conclusion
PCP can have significant negative effects on both the kidney graft and life of the patient. Risk factors include male gender, CMV infection and no antibiotic prophylaxis. Thus, adequate prophylaxis and early intervention and appropriate treatment are crucial to achieving good outcome.
Level of evidence:
This is a retrospective observational study, and thus the level of evidence is 3.
1. Please summarise this article.
Introduction
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immune-compromised hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
PCP is an important cause of morbidity and mortality in kidney transplant recipients and important cause of long-term graft failure. The effect of PCP on graft rejection and overall graft outcomes has been less explored.
This article analysed impacts of pneumocystis jirovecii pneumonia kidney transplant.
Methods
– Retrospective observational study analysed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
– Data collected: demographics, pretransplant status (cause of ESRD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy, PCP diagnosis (based on CXR and PCR or direct IF staining), CMV positivity.
– Graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
– Primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
– Secondary outcome was all-cause mortality
– Biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded.
– Protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
– Indication biopsies were also done, when suspected rejection or graft dysfunction,
Results
The primary outcomes were death censored graft failure, secondary outcomes were all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). Protocol biopsy were performed “0” hour, post-transplantation day-10, at one year, yearly thereafter.
All the recipient were male, with no history of prophylaxes. The result showed that CMV positivity and lack of use of prophylaxes was associated more with PCP infection.
Around 14% of PCP positive patients had graft failure, higher mortality at a median follow-up of 6.2years (infection rate 6.8 cases per 1000 per person-years).
Discussion and conclusion;
The study found male gender, CMV positivity were at higher risk of developing PCP, while oral use of antibiotic was associated with decreased risk of PCP.
PCP infection has increased risk of mortality and biopsy proven graft loss with AMR, T-cell mediated rejection and IFTA.
So prophylaxes is recommended to prevent PCP and risk graft failure.
2. What is the level of evidence provided by this article?
Level III
1.Sumarise
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts. And the aim of this study is to evaluate the impact of Pneumocystis jirovecii on long-term graft outcome.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
The main results of the study were:
– male gender and CMV positivity were risk factors associated with PCP;
– the use of oral prophylactic antibiotics seemed to prevent the risk of PCP;
– PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
– the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipien
– Pre-transplant dialysis was newly identified as a protective factor of PCP.
Thus, a more vigorous prophylaxis can bring better results.
2,What is the level of evidence provided by this article?
This is a retrospective study, lika a case control – level 03.
Introduction
This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients and important cause of long term graft failure and mortality.
Methods
– Retrospective observational study
–Analysed 1502 adult patients transplanted between 2000 and 2017
–Data collected included demographics, pretransplant status (cause of ESKD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy exposure, PCP diagnosis (based on CXR and PCR or direct immunofluorescence staining), CMV positivity
–Primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
–Secondary outcome was all-cause mortality
–Data on biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded
–Protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
–Indication biopsies were also done.
Results
The primary outcomes was death censored graft failure, secondary outcomes was all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). These protocol biopsy were performed zero time post-transplantation, on the day, and one year, there after every year.
All the recipient were male, with no history of prophylaxes. The result showed that CMV positivety and lack of use of prophylaxes was more associated with PCP infection.
Around 14% of PCP positive patients had graft failure, and higher mortality.
The median duration of follow-up was 6.2years and they found an infected rate of 6.8 cases per 1000 per person-years.
Conclusion
PCP has long been a risk factor. -Term transplant rejection and mortality with or without rejection. Therefore, proper prevention and treatment are necessary to avoid the side effects of PCP transplantation.
Level III evidence
The article deals with how pneumocystis jirovecii pneumonia is affecting kidney transplant. PCP is an important underlying cause of morbidity and mortality in recipient of kidney transplant.
Discussion
The article relies on a retrospective observational study which analyzed kidney transplant recipients in Seoul between 2000 & 2017.
From total participants , 68 developed PCP following transplant. Risk factors included CMV positivity and lack of initial prophylaxis.
The causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in vulnerable immunocompromised patients. It can affect kidney transplant recipients without prophylaxis and can lead to mortalities in up to 50% of those affected even with aggressive antibiotic treatment.
This organism cannot be cultured, so its life cycle is not known.
An important risk factors is CMV infection; as CMV can manipulate host immune response, resulting in suppression of the immune system. The pathogen enhances aging of host T cells, resulting in increased possibility of PCP and decreasing rate of infection recovery. Co-infection can worsen pulmonary affection..
Antibiotic therapy and prior transplant dialysis are protective against PCP. Pre transplant amelioration of uremia decreases the risk of PCP following transplantation.
Adequate prophylaxis should be for 3-6 months following transplantation.
Conclusion
PCP has considerable negative impact on both kidney graft and patient survival. Risk factors include male gender, infection with CMV and no measure of antibiotic prophylaxis. So, good prophylaxis and early management with proper treatment are essential for better outcomes.
Level of evidence:
level of evidence is 3;retrospective observational study.
. Summary;
PCP remains an important cause of morbidity and mortality in kidney transplant recipient.
This is infection of immunocompromissed patients, with development of strong immunosuppression these patients are prone to develop opportunistic infections.
According to literature the infections are second most factor in mortality and morbidity of these patients.
The incidence of PCP varies but it’s around 0.6 to 14% among kidney transplant patients without prophylaxes and with a mortality of 50%.
Methods;
This was a retrospective observational study done at Seoul National hospital in 2017, number of patients were 2000, of them have received dual kidney-pancreas and kidney-liver transplantation.
Data collection;
Data collected from kidney recipient were collected from the electronic medical records.
Demographic characteristic were age, height, weight, gender, BMI were taken. Other duration of transplantation, cause of renal failure, and other co-morbidities were collected.
Results
PCP and transplant outcomes;
The primary outcomes was death censored graft failure, secondary outcomes was all cause mortality, and biopsy proven (ABMR, T-cell mediated rejection, IFTA). These protocol biopsy were performed zero time post-transplantation, on the day, and one year, there after every year.
All the recipient were male, with no history of prophylaxes. The result showed that CMV positivety and lack of use of prophylaxes was more associated with PCP infection.
Around 14% of PCP positive patients had graft failure, and higher mortality.
The median duration of follow-up was 6.2years and they found an infected rate of 6.8 cases per 1000 per person-years.
Discussion and conclusion;
The study found male gender, CMV positivity were at higher risk of developing PCP, while oral use of antibiotic was associated with decreased risk of PCP.
PCP infection has increased risk of mortality and biopsy proven graft loss with AMR, T-cell mediated rejection and IFTA.
So prophylaxes is recommended to prevent PCP and risk graft failure.
Level of study III
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts
Methods
Study design and subjects
The study design was approved by the institutional review board of Seoul National University Hospital (no. H1805-173-948) and complied with the Declaration of Helsinki. This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records. Demographic characteristics including age, gender, height, weight, and body mass index were collected. Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes, was evaluated.
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018. Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected. Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter. Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
Baseline characteristics and risk factor of PCP
The median duration of follow-up was 6.2 years (interquartile range, 3.0–9.6 years; maximum 18.3 years). Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months (interquartile range, 3.9– 10.0 months), and 79.4% of cases developed during the first year after transplantation. There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
PCP and transplant outcomes
We performed propensity score matching to mitigate the difference in baseline characteristics between the PCP-positive and -negative groups. All the patients were male and had no history of prophylactic antibiotics usage after transplantation. During the admission period, 8 of 9 patients (88.9%) experienced acute kidney injury according to the Kidney Disease Improving Global Outcomes criteria and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP. To determine the cause of the elevated risk of graft failure, we evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs. However, these outcomes did not differ between PCP-positive and –negative groups.
During the follow-up period, 11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and -negative groups, respectively. The 28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%). All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
Discussion
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured
Due to little knowledge about Pneumocystis jirovecii, it is necessary to investigate whether the long term effect of PCP on allografts is due to the infection alone or with chronic inflammatory process and other unknown mechanisms.
Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. Nevertheless, occurrence of PCP was significantly associated with overall graft failure. As has been previously demonstrated, viral infections such as CMV, BK virus, and hepatitis C virus, and certain bacterial infections such as Pseudomonas aeruginosa, affect allograft dysfunction by modulating non-immunological factors such as hemodynamic change in addition to immunological factors
there are some limitations. First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively. Nevertheless, the study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes. Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects. The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes. However, this did not hinder the study purpose on the relationship between PCP and transplant outcomes.
Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure. The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
Level III
PCP is an oppurtunistic fungi that is present in the post transplant patient…the incidence is somewhere between 0-14%… Infection is the second commonest cause of death with the functioning graft after cardiovascular diseases after transplant… The Association between CMV and BKV for graft rejection is established due to the immunomodulation effect of the viruses…The observational retrospective study conducted in university of Seoul….The study included 1827 kidney transplant patient between Jan 2000 to Dec 2017..They evaluated for graft and survival outcome between those who had PCP and those without PCP infection….
Exclusion criteria were patients less than 18 years old and those with simultaneous kidney pancreas transplant or kidney liver transplants…After the exclusion remaining 1502 patients were finally included for ananlysis .. PCP was defined as clinical suspisicon + PCR for PCP positivity or IF stain on BAL or sputum…Initial use of prophylactic antibiotic was defined was prescription of TMP-SMX for 4 weeks atleast…. CMV positivity was also defined in the study as more than 20 copies/ml on PCR….
Primary outcome of the study was return to dialysis or transplantation….The secondary outcome of the study was all cause mortality….. There was a protocol biopsy done at the time of the transplant on day 0 and 1 year post transplantation and alternate year thereafter…
The median follow up was 6.2 years with 4.5% of the patients having PCP post transplant…. The average time to develop PCP in this study was 5.2 months….
The results showed that male gender and CMV positivity and lack of use of prophylaxsis was associated with more PCP…..
Around 14% of the PCP positive patients had graft failure….. The graft failure episodes were attributed to concurrent AKI factors and not related to immunological factors
They also found that PCP positive cohort had overall higher mortality…
Limitation of the study are it is a retrospective study and the cause effect relationship between PCP and mortality cannot be established…. The study also used oral antibiotics for 1 month duration only as compared to 3-6 months recommended by KDIGO
The level of evidence is level 3 only
This is a retrospective observational study which was approved by the institutional review board of Seoul National University Hospital. This study included 1827 kidney transplanted patients at Seoul National University Hospital from January 2000 to December 2017 evaluated for graft and survival outcome between those who have Pneumocystis jiroveci pneumonia infection and those have no Pneumocystis jiroveci pneumonia infection.. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded. Consequently, the remaining 1502 patients were finally included and their data were reviewed.
They found that male gender and CMV positivity were risk factors associated with PCP infection and prevented by oral prophylactic antibiotics.
PCP infection was associated with both graft failure and overall mortality.
recommendations for intensive tratment and prophylaxis.
Introduction :Infection is an important factor in relation to the risk
of death in kidney transplant recipients, and the second
most common cause of death after cardiovascular dis-
ease in patients with functioning grafts.Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocom-
promized hosts.The incidence of P. jirovecii pneu-
monia (PCP) varies from 0.6 to 14% among kidney
transplant recipients without prophylaxis, with a mortal-
ity of up to 50% despite aggressive antibiotic therapy.
In this study, evaluation of the impact of PCP on
kidney transplant outcomes, including graft failure and
rejection done.
Method :This retrospective observational study included
total 1827 patients who had kidney transplantation at
Seoul National University Hospital from January 2000 to
December 2017.The primary outcome was death-censored graft failure
defined as a return to dialysis or kidney re-
transplantation. The secondary outcome was all-cause mortality.
Result :Among 68 PCP-positive
recipients, 9 (13.2%) patieIntroduction :Infection is an important factor in relation to the risknts developed death-censored
graft failure.During the follow-up period, 11 patients (16.2%) and
13 patients (11.0%) died in the PCP-positive and
-negative groups, respectively. The 28 PCP-positive pa-
tients had concurrent other infectious diseases, and 8
patients died (28.6%). All-cause mortality was higher in
the PCP-positive group than in the PCP-negative group.
Conclusion :All-cause mortality was higher in
the PCP-positive group than in the PCP-negative group.It is related to increased,morbidity,mortality in transplant patient.
Level of Evidence :This is a retrospective observational study, and thus the level of evidence is 3
Summary
Introduction
This article is concerned with how pneumocystis jirovecii pneumonia impacts kidney transplant. PCP is an important cause of morbidity and mortality in kidney transplant recipients.
Discussion
The given article is based on a retrospective observational study which analyzed kidney transplant recipients in Seoul between the years of 2000 and 2017.
Out of the total participants of the base study, 68 developed PCP post transplant. Risk factors were found to be CMV positivity and lack of initial antibiotic prophylaxis.
About the causative organism : Pneumocystis jirovecii is an opportunistic fungi causing pulmonary infection in immunocompromised people. It can affect kidney transplant recipients who do not have prophylaxis and can cause fatalities in upto 50% of those affected even with aggressive antibiotic cover.
This fungi cannot be consistently cultured, and thus its life cycle is not known.
One of the major risk factors includes CMV infection. This is because CMV can modify host immune response, thus leading to suppression of the immune system. The pathogen accelerates aging of host T cells, thus increasing vulnerability to PCP and decreasing rate of infection resolution. This is also why co-infection can worsen pulmonary impairment.
Antibiotic cover and pre transplant dialysis are protective factors against PCP. Pre transplant resolution of uremia lowers the risk of PCP in the post transplant period.
Adequate prophylaxis needs to be for a period of 3-6 months post transplantation.
Conclusion
PCP can have significant negative effects on both the kidney graft and life of the patient. Risk factors include male gender, CMV infection and no antibiotic prophylaxis. Thus, adequate prophylaxis and early intervention and appropriate treatment are crucial to achieving good outcome.
Level of evidence
This is a retrospective observational study, and thus the level of evidence is 3.
EFFECT OF PJP ON KIDNEY TRANSPLANT
background-
cardiovascular and infection is most commom cause of death after transplant
PJP is seen in 0.6 to 14 % of transplant without prophylaxis and 50% mortality
BKV and CMV is associated with rejection and graft loss BUT little is known about PJP and rejection risk and graft function
study
retrospective
in korea
1827 kidney transplants
1502 included afted excluding less than 18 yrs , SPK liverand kidnet tx
diagnosis of PCP
. PCP was defined as the presence of findings suspicious of PCP
detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase
chain reaction or direct immunofluorescence stain of
sputum or bronchoalveolar lavage fluid
PCP
4 weeks after transplant with bactrim
outcome was eath censored graft failure
retransplant or return to dialysis
protocol biopsy as well as indication biopsy done
results
68(4/5%0 had PCP
80% IN FIRST year
median follow up 6.2 yrs
pcp and graft outcome
9 out of 68 had graft failure
significant relationship was found between graft failure and PCP positivity
all patients were MALE
NO PCP received
8 out of 9 has AKI
PCP do not increases the risk of rejection , IFTA , DSA
non immunological cause for graft loss associated with PCP
RISK FACTORS
make gender
CMV positivity
absence of PCP
PJP is associated with graft loss and death
pre transplant dialysis may protect againg PJP – furtehr study is required
PCP is MUST for 3-6 months after transplant
LIMITATION OF STUDY
retrospective
1 month of PCP given which is less than standard
LEVEL 3 STUDY
Introduction
· With the improvement of immunosuppressive regimens, graft loss became less, but the mortality rates in patients with functioning grafts remain unchanged
· Infection is the second most common cause of death after cardiovascular disease in recipients with functioning grafts
· Pneumocystis jirovecii pneumonia is an opportunistic infection occurs in immunocompromized patients with an incidence of 0.6-14% among kidney transplant recipients without prophylaxis, and a mortality of up to 50% despite aggressive antibiotic therapy
· This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods
· Inclusion criteria: Total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017, with final number 1502 patients.
· Exclusion criteria: 1) Patients who were under 18 years old, 2) Patients who received simultaneous kidney–pancreas or kidney–liver transplants
· Data from the kidney transplant recipients were collected from the electronic medical records.
· PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest CT combined with + PCP or direct immunofluorescence stain of sputum or BAL fluid
· Prophylaxis with trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
· CMV infection considered + if PCR is > 20 copies/ml
Discussion
· This study found that male gender and CMV positivity were risk factors for PCP, and the use of oral prophylactic antibiotics may to prevent the risk of PCP
· PCP increased the risk of long-term graft failure; but this was not related to rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
· As PCP was associated with graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
· CMV infection was found to increases a risk of PCP
· Pre-transplant dialysis was newly identified as a protective factor of PCP as uremia alter the immunological responses
Limitations of the study
· It was a retrospective, making it difficult to demonstrate cause and effect definitively.
· The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
· The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes.
· The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion
· Male gender, positive CMV, and non-use of oral prophylactic antibiotics, are risk factors for PCP
· PCP increases the risks of mortality and graft failure
· Prophylaxis is recommended to prevent PCP and subsequent graft failure.
This is a retrospective study level 3
Among infections in kidney transplant recipients, PCP is an important cause of mortality & morbidity. Though certain infections like CMV, BK virus have an association with acute rejection & poor graft survival in early post transplant period, but there is little known in case of PCP infection. This retrospective observational study analyzed 1502 kidney transplant recipient patients at Seoul National University between 2000 and 2017. Total 68 patients developed PCP after transplantation & multivariable cox analysis showed CMV positivity & absence of antibiotic prophylaxis were the risk factors. The PCP positive group had a higher hazard ratio of graft failure compared to PCP negative group but PCP infection does not showed with subsequent development of DSA, rejection and IFTA.
Level of evidence was 3 in this article.
I. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Summarise this article
Backgound
– Cardiovascular disease and infections are the leading causes of mortality among kidney transplant recipients.
– PCP is a significant cause of morbidity and mortality in kidney transplant recipients.
– Among kidney transplant recipients without prophylaxis, incidence of PCP varies from 0.6-1.4%.
– A 50% mortality is reported despite aggressive antibiotic therapy.
Methods
– Retrospective observational study
– analysed 1502 adult patients transplanted between 2000 and 2017
– data collected included demographics, pretransplant status (cause of ESKD, comorbidities, type and duration of dialysis, prior transplant), ABO compatibility, HLA typing, immunosuppressive therapy exposure, PCP diagnosis (based on CXR and PCR or direct immunofluorescence staining), CMV positivity
– primary outcome was death-censored graft failure defined as a return to dialysis or kidney transplantation
– secondary outcome was all-cause mortality
– data on biopsy-proven acute TCMR, ABMR, IFTA and DSAs was recorded
– protocol biopsies done at time zero (post-reperfusion), day 10, 1-year post-transplant and annually thereafter
– indication biopsies were also done
Results
– out of the 1502 patients, 68 patients (4.5%) developed PCP post kidney transplantation
– median time to develop PCP was 5.2months and 79.4% of patients developed PCP during the 1st year following transplantation
– CMV positivity and lack of antibiotic prophylaxis were associated with an increased risk of PCP
– of the 68 PCP-positive patients, 9 developed death-censored graft failure
– the PCP-positive group was at increased risk of graft failure and mortality compared to the PCP-negative group
– PCP infection was not associated with subsequent development of de novo DSAs or pathologic features of TCMR, ABMR or IFTA on kidney biopsy suggesting that the graft failure rates were not attributable to the immunological transplant episodes
– in the follow up period, 11 patients (16.2%) died in the PCP-positive group compared to 13patients (11%) in the PCP-negative group
– the 28 PCP-positive recipients had concurrent infectious diseases and 8 patients (28.6%) died
– all-cause mortality was higher in the PCP-positive group compared to the PCP-negative group
– the commonest cause of death was ARDS related with PCP
Discussion
– much remains unknown regarding PCP i.e., the lifecycle, epidemiology, clinical implications, whether the long-term effects on the graft are due to the infection alone or due to chronic inflammation or other unknown mechanisms
– male sex and CMV positivity were associated with PCP
– use of antibiotic prophylaxis prevents the risk of PCP
– PCP increased the risk of long-term graft failure but this relationship was not dependent of rejection, IFTA or de novo DSAs
– intensive treatment and prophylaxis is recommended post-transplantation due to the increased risk of graft failure and mortality associated with PCP
– CMV infection modifies the host immune response hence it can increase the risk of PCP
– pretransplant dialysis has been identified as a protective factor of PCP – uremia alters immunological responses hence pretransplant resolution of uremia decreases the risk of post-transplant PCP
– occurrence of PCP does not affect the risk of developing acute rejection and production of de novo DSAs
– PCP was associated with overall graft failure
– viral infections (e..g., CMV, BKV, HCV) and some bacterial infections (e.g., pseudomonas aeruginosa) modulate non-immunological and immunological factors hence affecting graft dysfunction
– PCP did not increase risk of rejection meaning that nonimmunological factors may be the cause of these observations
– PCP infection can cause AKI and can also stimulate production of proinflammatory cytokines (e.g., IL-1, IL-6, IL-8) hence inducing graft injury
– mortality rate was high in PCP-positive patients
– 81.8% patients died within 3 months of PCP diagnosis, with the cause of death being PCP itself or other superimposed infections
– given these outcomes, PCP prophylaxis is strongly recommended
– KDIGO recommends PCP prophylaxis for 3-6months following transplantation
Study limitations
– retrospective study hence difficult to demonstrate cause and effect confidently
– observational study design hence cannot determine the mechanisms underlying the risk and the subsequent effect of PCP
– definition of antibiotic prophylaxis as 1 month – this is shorter than what is recommended in the guidelines i.e., 3-6 months
Conclusion
– male sex, CMV positivity and lack of antibiotic prophylaxis increase the risk of PCP
– PCP increases risk of graft failure and mortality
– antibiotic prophylaxis is needed to prevent PCP and subsequent graft failure
Level of evidence provided by this article
– Level III
IMPACT OF PCP ON KIDNEY TRANSPLANT OUTCOMES.
BACKGROUND.
-Infection rank 2nd after cardiovascular dx as a cause of mortality post transplant. PCP incidence post transplant is 0.6-14% in KTR with no prophylaxis with mortality of upto 50%.The impact of PCP on graft dysfunction and mortality is well explored. This study looked into effects of PCP on KTR including graft dysfunction and rejection.
METHODS.
-Retrospective observational study on 1827 pts transplanted at Seoul National University Jan 2000 – Dec 2017.
-Exclusion -Pts < 18 yrs
-Those with simultaneous Pancreas and Kidney Transplant.
-Data was electronically collected.
-PCP was defined as presence of suspicious finding of PCP by a radiologist + PCP PCR or IF stain on sputum or BAL.
-Initial use of prophylactic antibiotics was defined as prescription of septrin > 4 weeks one month post transplant.
-CMV positivity was taken as > 20 copies /ml on PCR or +VE results on viral cultures.
-Primary outcomes; Return to dialysis or kidney transplantation.
-Secondary outcome – All cause mortality.
-Protocol biopsy done at zero time post perfusion on 0/7 and 1 yr post transplantation and alternate year thereafter.
-All analysis was done with stata software.
-Data expressed as mean +/- SD for continuous variables, Categorical variables on baselines xtics were done using x2 and fisher exact test with continuous variables analyzed with student T test.
-A P value of <0.05 was interpreted to be statistically significant.
RESULTS.
-Median follow up was 6.2 yrs with 4.5 % having PCP post transplant.
-Median time to develop PCP was 5.2 months.
-CMV positivity and no use of prophylactic antibiotics were associated with more PCP, equally more males had PCP than females.
-13.2% of PCP +VE pts had graft failure.
-Graft failure amongst pts with PCP was possibly from non immunological factors like concurrent AKI and not typical immunological transplant episodes,
-PCP +VE group had a higher risk of mortality than PCP -VE cohort.
DISCUSSION.
-Male gender and CMV positivity are risk factors for PCP while prophylactic antibiotics seemed to be protective against PCP.
-Due to increased risk of graft dysfunction and mortality ,intensive treatment and prophylaxis recommended post transplant.
-In this study, pre transplant dialysis was found to reduce risk of PCP unlike other studies but this should not be done over a long duration pre transplant. Further studies are needed on pre transplant hemodialysis.
-As per KIDIGO ,PCP prophylaxis should be 3-6/12 post transplant. More studies needed on this.
LIMITATIONS.
-Retrospective study-Difficult to show cause and effects of PCP with certainty.
-Short duration of prophylactic antibiotics in study vs guidelines (1 vs 3-6/12).
-Pathophysiology behind effects of PCP not established.
CONCLUSION.
-Male gender, no prophylaxis and CMV positivity are risk factors to PCP post transplant. More studies needed in future to guide prophylaxis use post kidney transplant.
LEVEL OF EVIDENCE – RETROSPECTIVE – LEVEL 3.
Summary:
Introduction:
Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in kidney transplant recipients. The incidence ranges from 0.6-14% with a mortality rate up to 50%.
Methods:
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
This study included total 1827 patients who had kidney transplantation. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65), total 325 were excluded. PCP positive and PCP negative groups were studied, and graft outcomes and patient survival were compared between groups.
Results: A total of 68 patients (4.5%) developed PCP after transplantation. The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusion: Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases Fig. 2 Patient survival curves in the PCP-positive and -negative patients. P value was obtained using the log-rank test. Dashed line, PCP-positive; solid line, PCP-negative Kim et al. BMC Nephrology (2019) 20:212 Page 6 of 8 both the risks of mortality and graft failure.
Level of evidence: Level 3
Retrospective observational study
level of evidence 3
This retrospective observational study conducted by Kim and his colleagues at Seoul National university hospital looked at an important aspect of long term graft outcome in patients developing PJP during course of illness.
They analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
They found that total of 68 patients (4.5%) developed PCP after transplantation. The risk factors for developing PJP were CMV and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
This study confirms the fact that PJP prophylaxis is mandatory for all transplant patients and occurrence of PJP is associated with reduced long term graft survival and mortality.
Abstract:
Backgrounds: Pneumocystis jirovecii pneumonia (PCP) IS important cause of morbidity and mortality in
kidney transplant recipients.
Method: retrospective observational study
Result: the positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis are risk factors of post-transplant PCP. The PCP-positive group had higher risk of graft failure and mortality than the PCP-negative group. the PCP infection is not related with subsequent development of de novo donor-specific antibodies or pathologic findings, of T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Conclusions: PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
Background:
Infection is an important factor for death in kidney transplant recipients, and the second most common cause of death after CVD in patients with functioning grafts .
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts.
The incidence of P. (PCP) is 0.6 to 14% without prophylaxis, with a mortalityof 50% despite aggressive treatment .
Certain infections like (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period . therefore appropriate infection prophylaxis and treatment regimens could be implemented to reduce immunological complications.
Results:
The infection rate is 6.8 cases per 1000 person-years. The median time to the development
of PCP was 5.2 months , and 79.4% of cases developed during the first year after transplantation.
Ø CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP .
Ø the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients .
To determine the cause of graft failure, this study evaluated the effect of PCP on the rejection, interstitial fibrosis and tubularatrophy, and de novo DSAs. But these did not differ between PCP-positive and –negativegroups . These results suggest that different graft failure rates is not due the conventional immunological transplant episodes, but could be due to non-immunological factors such as concurrent acute kidney injury.
Ø All-cause mortality was higher in the PCP-positive than in the PCP-negative .
Ø 81.8% died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion:
Ø Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown.
Ø The epidemiology of human PCP is unclear yet .
Ø Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
Ø The results of the present study demon stated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
Ø Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
Ø Previous studies demonesrate that CMV infection increases a risk of PCP, it is supported by the present stusy . This may be because CMV might modify the host immune response, leading to immune suppression.
Ø Pre-transplant dialysis was newly identified as a protective factor of PCP in this study. Accordingly, appropriate pre-transplant resolution of uremia would decrease the risk of post-transplant PCP.
Ø But , a long-term pre-transplant dialysis negatively affects the host immune status .
Ø The PCP itself did not affect the risk of of acute rejection and de novo DSA production. But PCP was significantly associated with overall graft failure. infections such as CMV, BK virus, and hepatitis C virus, and Pseudomonas aeruginosa, affect allograft dysfunction by modulating non-immunological factors such as hemodynamic change in addition to immunological factors . In this study , PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Ø Mortality risk was elevated in patients with PCP.
Ø prophylaxis against PCP may be strongly recommended.
Ø According to the KDIGO guideline, it is recommended that all recipients receive prophylaxis against PCP for 3–6months after transplantation .
Limitations of this study.
Ø First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively.
Ø Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Ø Lastly, the present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion:
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
LEVEL 3 retrospective study .
This article analyses the impact of Pneumocystis Jirovecii pneumonia on the outcomes of kidney transplantation.
INTRODUCTION
Post transplant infections play a major role in deciding transplant outcomes. Even with more and more advancement in immunosuppression and newer management protocols, the incidence of infections has remained steady over last 15 years. Rather with advent of more potent immunosuppression, risk of infections, viral, fungal and bacterial has increased.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
impact of PCP on kidney transplant outcomes, including graft failure and rejection were evaluated in this study.
METHODS
This is a retrospective observational study which included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
Transplant outcomes:
1. Death-censored graft failure defined as a return to dialysis or kidney re-transplantation.
2. All-cause mortality.
RESULTS
1. Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
2. The median time to the development of PCP was 5.2 months
3. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
4. PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 [1.14–8.26]); P = 0.027).
5. All-cause mortality was higher in the PCP-positive group than in the PCP-negative group.
6. Pre-transplant dialysis was newly identified as a protective factor of PCP
DISCUSSION
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured. It is necessary to investigate whether the long term effect of PCP on allografts is due to the infection alone or with chronic inflammatory process and other unknown mechanisms.
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. However, occurrence of PCP was significantly associated with overall graft failure.
Mortality risk and is significantly increased whereas graft outome becomes poor in patients with PCP. Hence, prophylaxis for PCP after transplantation is recommended for all patients for a period of 3-6 months post transplantation.
LIMITATIONS
1. Reterospective study makes it difficult to demonstrate, cause and effect definitively.
2. The definition of prophylaxis against PCP was 1 month, which is less than the recommended guideline of 3-6 months.
3. the study could not identify the mechanisms underlying the risk and subsequent effect of PCP.
LEVEL OF EVIDENCE: LEVEL 3
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts .
The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
Certain infections such as cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods
Data collection and definitions
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infection
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation. The secondary outcome was all-cause mortality.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected.
The development of de novo donor-specific antibody (DSA) was defined as any newly developed anti-HLA class I or II antibody.
Results
Baseline characteristics and risk factor of PCP
The median duration of follow-up was 6.2 years.
4.5% experienced PCP after kidney transplantation.
The median time to the development of PCP was 5.2 months and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
PCP and transplant outcomes
13.2% patients developed death-censored graft failure.
univariable and multivariable analyses showed a significant relationship between PCP and graft failure.
Although the acute T cell-mediated and antibody-mediated rejection episodes or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted, the PCP-positive recipients had a higher risk of deathcensored graft failure than the PCP-negative recipients.
The clinical information on the PCP-positive patients with graft failure.
All the patients were male and had no history of prophylactic antibiotics usage after transplantation.
88.9% experienced acute kidney injury according to the Kidney Disease Improving Global Outcomes criteria and (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
The outcomes did not differ between PCP-positive and –negative groups .The results suggest that different graft failure rates might not be attributable to the conventional immunological transplant episodes, but might be related with non-immunological factors such as concurrent acute kidney injury.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group .
The PCP-positive group had a higher risk of mortality than the PCP-negative group.
81.8% died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion
The results of the present study demonstrated that
The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production. Nevertheless, occurrence of PCP was significantly associated with overall graft failure.
PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Certain PCP-positive patients had concurrent acute kidney injury and half of them did not achieve the recovery from this condition, which might leave the grafts with non-immunological damages.
However, through non-immunological pathways, infections may also induce allograft injury by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8 These proinflammatory cytokines are known to be upregulated in patients with PCP.
81.8% patients died within 3 months after diagnosis of PCP infection. The causes of death in these patients were either PCP itself or the other infection superimposed on PCP.
There are some limitations of this study .
First, it was a retrospective study, making it difficult to demonstrate cause and effect definitively. Nevertheless, the study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes. Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Lastly, the present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure. Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure. The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
level of evidence
retrospective analysis level of evidence III
·Summmary of Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome Introduction
· PCP remains a serious opportunistic infection in heavily immunocompromised patients who are not taking chemoprophylaxis.
· The organism
· A group of fungi named Archi ascomycetes has only one copy of nuclear ribosomal RNA and a fragile cell wall and contains little or no ergosterol.
· Transmission of infection
· P-jirovecii can not be cultured in vitro.
· Human hosts can be infected with more than one strain of pneumocystis jirovecii, so the possibility that infection can be acquired on multiple occasions.
· Drug treatment
· The main drug classes used for treatment and prophylaxis of PCP included antifolate drugs ,diamines, atovaquone, and macrolides.
· TMP-SMX is as effective as interim pentamidine for therapy.
· TMP-SMX is the most effective chemoprophylaxis.
· Other medications for the treatment of PCP are Sulfadiazine plus pyrimethamine ,atovaquone, clindamycin plus pyrimethamine e, trimetrexate, dapsone, and aerosolized pentamidine.
· Medication effective for prophylaxis are :
· Dapsone. Dapsone-trimethoprim, atovaquone, aerosolized pentamidine, pentamidine, and clindamycin-primaquine are not effective for prophylaxis.
· PCP prophylaxis for HIV -infected patients with CD4 less than 200 cell/min.
· 80/400 mg TMP-SMX daily appears to be equally effective and associated with fewer side effects than 160/800 mgdialy.
· Tolerability may improve with lower doses of the intermittent regimen.
· Treatment of PCP
· The mortality rates decrease to 5-15%recently as earlier diagnoses and treatment of the PCP infection and the introduction of corticosteroids to patients with moderate to severe PCP if oxygen is less 70 mmHg.
· Sulpha drugs are a structural analogy of PABA and inhibit DHPS.
· In the only non-crossover trial TMP-SMX was associated with better survival than pentamidine survival than pentamidine.
· Adverse affect occurs after 7 days of therapy including rash,fever,leukopenia,hepatotoxicity, and interstitial nephritis plus renal calculus formation.
· Anaphylactic reaction and pancreatitis can occurs.
· Trimethoprim can cause hyperkalemia
· Pentamidine to avoid serious fatal complications slowed and administrated slowly by intravenous infusion .
· Inhaled pentamidine can be used for therapy but it has poor efficacy .
· Side effects of pentamidine:
· Glommular and tubular damage.
· Toxic to the pancreas that can result in hypoglycaemia .
· leukopania
· prolong QT interval
· alternative for the for the TMP-SMX and pentamidine :
· dapsone -pentamidine ,clindamycin -primaquine and atovaquone
· .Atovaquone is a good alternative to TMP-SMX for patients with mild disease who can not tolerate TMP-SMX..duration in HIV-negative is 2 . and HIV positive is 3 weeks.
· Sulphonamide Resistance
· In a retrospective study, TMP-SMX resistance was more than twice as likely in blood cultures from HIV patients receiving TMP-SMX compared to patients not receiving this prophylaxis .
Sulfa Resistance
· An organism is caused by a mutation in the primary sequence of the DHPs gene .
· Two recent results reported the double DHPs mutation.Th55Ala and Pro57 ser result in an absolute requirement for PABA.
· The clinical significance of DHPs mutation, with regard to response to prophylaxis and therapy using asulfa based regimen has been controversial.
· There is evidence to suggest the contributory role for DHPs mutation in breakthrough PCP in patients using alternative sulfa prophylaxis .
· DHFR Resistance
In Trimethoprim in vitro , the combination of trimetrexate and sulfamethoxazole may be amore potent combination than trimethoprim plus sulfamethoxazole. However, no clinical data support this.
Limitation of this study
· The absence of a culture system precluded standard susceptibility testing and limited, the understanding of many fundamental aspects of the organism.
· Absence of definition of clinical failure
· High incidence of adverse effects by the treatment of PCP which included fever caused by infection or treatment.
· Non adherence is presumed failure of prophylaxis may be difficult to access. Although several studies have reported DHFR mutation ,there is so far no evidence that the wide spread use of TMP-SMX have caused emergency of clinical significant resistance to DHFR inhibitors.
· Atovaquone
· It has high number of mutation about 7 which can be explained by ahigh mutation rate and impaired proof reading of mitochondrial genes.
· Survival the same inpatients with or without mutation
· Pentamidine and clindamycin-primaquine:
· are used for presentation and treatment of PCP but possible resistance mechanism have yet to be discussed and reported.
· Conclusion
· Mutation in sulfa and atovaquone drug resistance in P.jirovecii as a result of selective pressure by the widespread use of PCP prophylaxis .
· But there is no firm evidence that DHPs mutation in result in significant resistance to high dose sulfa thearpy.
· Investigation into the mechanism of drug resistance and identification of new moleucular target are continuing..
· These data is crucial for further understanding of the infection and will enable identification of new polymorphic regions and drug targets and may eventually also lead to the development of aculture system.
leve evidence 5
Introduction
Infection is an important risk factor of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts. P. jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts. Among kidney transplant patients without prophylaxis, the incidence of P. jiroveciipneumonia (PCP) ranges from 0.6 to 14%, and a morality of 50% despite aggressive antibiotic therapy. This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods
It was a retrospective observational study, which included 1827 patients who had kidney transplantation at Seoul National University Hospital, from January 2000 to December 2017. Patients under 18 years and patients who received two simultaneous transplants were excluded, and consequently 1502 patients were finally included. Data from the patients was collected from electronic medical records. Demographic characteristics included age, weight, gender, height and body mass index were collected. Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure and comorbidities such as hypertension and diabetes was evaluated. The Abo and HLA compatibility was also evaluated and immunosuppression therapy was determined. PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest CT and PCP positive PCR on sputum or bronchoalveolar lavage fluid. Patients were prescribed oral prophylaxis for the first 4 weeks after transplantation, trimethoprim/sulfamethoxazole.
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney re-transplantation.
The secondary outcome was all-cause mortality. All patients were followed up until graft failure or March 2018. Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection and interstitial fibrosis and tubular atrophy were collected. Protocol biopsies were performed at zero-time, on the 10thday and 1 year after transplantation, and every year thereafter.
Results
Of the 1502 patients, 68 patients experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 persons-years. The median time to the development of PCP was 5.2 months, and 79.4% of the cases developed during the first year after transplantation. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Among the 68 PCP positive patients, 9 patients developed death-censored graft failure. The PCP-positive recipients had a higher risk of death-censored graft failure than PCP-negative kidney transplant recipients. 28 of the PCP positive patients had other infections concurrently, and 8 of these patients died. All-cause mortality was higher in the PCP-positive group than the PCP-negative group. The PCP-negative group had a higher risk of mortality than the PCP-negative group. The most common cause of death of the PCP-positive patients was acute respiratory distress syndrome related with PCP.
Discussion
P. jiroveciiis an opportunistic fungus, and its lifecycle remains unknown as it cannot be cultured. It is imperative to further understand the role of PCP on allografts. The results of the study demonstrated that the male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics reduced the risk of PCP. The occurrence of PCP increased the risk of long-term graft failure. As PCP was associated with graft failure and overall mortality, intensive treatment and prophylaxis is recommended after kidney transplantation. The results also noted that PCP did not increase the risk of rejection after infection. This may be because non-immunological factors may be the cause of the findings. It was reported that the mortality risk was elevated in patients with PCP. Therefore, considering these findings, prophylaxis against PCP may be recommended. Further research is required on the definitive dosage and duration of prophylaxis.
Limitations
The limitations of the study include the retrospective approach and the current definition of the prophylactic antibiotics was one month, which is shorter than the guideline recommendation.
Level of Evidence:
This is a retrospective comparative study, therefore, the level of evidence is level III
INTRODUCTION
The pneumocystis jerovicii which is opportunistic infection that cause severe pulmonary infections in immunocopmromised patients .
The incidence of PCP varies from 0.6% to 14% among kidney transplant recipient who on not prophylaxis ,with mortality rate of up to 50%
all previous studies showing that PCP increase the mortality but with clear effect on graft function or graft survival .
In this study we need to know what is impact of PCP on kidney transplant outcome including graft failure and rejection.
METHOD
This study is retrospective observational analysed 1502 adult patients post kidney transplanted at seoul national univrersity hospital .this number of patients after exclude simultaneous kidney –liver or kidney –pancreas transplantation and also exclude who age under 18 years.
The study compare graft and survival outcome between PJP negative and PJP positive groups between January 2006 to December 2017( median duration of follow up 6.2 years).
RESULT
In the period of 6.2 years in total of 1502 patients 68 patients around 4.5% have affected by pneumocystis jerovecii pneumonia with an infection rate of 6.8 case per 1000 person in years.
The median time to the development of PCP was 5.2 months (interquartile range, 3.9–
10.0 months), and 79.4% of cases developed during the first year after transplantation. There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen ,HTN,and CMV positivity. After adjustment for multiple covariates, CMV positivity and when we not using prophylactic antibiotics all are associated with increasing risk of pneumocystis jerovecii pneumonia.
Graft failure in positive PCP was more than negative around 9 patient (13.2%).
Mortality rate was increase in positive PCP than negative PCP with hazard ratio (HR, 10.99).
There is no differences between positive PCP and negative PCP in development of denovo DSA and histopathological changes as interstitial fibrosis ,atrophy and T cell mediated rejections .
CONCLUSION
Male,CMV positivity and non using of prophylactic antibiotics are considering risk factors of PCP which is significantly increasing mortality and graft loss.
LEVEL OF EVEDENCE 3
Please summaries this article.
Introduction:
An opportunistic Fungal infection “Pneumocystis jirovecii” causes pneumonia (PCP) in immunocompromised cases including kidney transplant recipients.
The incidence rates range from 0.6-14% with a mortality rate up to 50% even with treatment in patients without PCP prophylaxis.
Methods:
This was a retrospective observational analysis of the effect of PCP infection on long term graft survival in kidney transplant recipients.
A total 1827 patients included with 325 exclusions leading to review of 1502 patients who underwent kidney transplant at Seoul National University Hospital from 2000 to 2017.
Two groups: PCP-positive, and PCP-negative groups were made, and graft outcomes and patient survival were compared between them.
Results:
1502 patients were followed for median of 6.2 years. out of which 68 (4.5%) patients developed PCP. Median time was 5.9 months to infection, out of which 79% developing PCP during their first year.
Risk factors for PCP were as follows.
In PCP-positive group 13% developed graft failure pointing towards increased risk of graft failure (hazard ratio 3.1). but important point was that all PCP-positive patients developing graft failure were males and had no PCP prophylaxis in the past. They also had associated acute kidney injury (AKI) at time of admission.
Increased risk of mortality was seen in PCP-positive group (hazard ratio 11) as compared to the PCP-negative group, with up to 80% mortality within 3 months of developing PCP.
Protective factors were use of prophylactic antibiotics, and pre-transplant dialysis. No difference was observed with respect to donor specific antibody (DSA) formation, acute rejection (suggesting non-immunological cause of graft failure), or interstitial fibrosis and tubular atrophy between the studied 2 groups.
Limitations:
To conclude, PCP in renal transplant recipients increases risk of graft loss and mortality, and hence adequate measures should be taken to prevent (by using oral prophylactic antibiotics) and aggressively treat PCP.
2. What is the level of evidence provided by this article?
This is level 3 evidence: because it was “retrospective case control study”.
Thank you
This is a retrospective observational study analysed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
After excluding paediatric patients (under 18 years old) and those who received simultaneous kidney–pancreas or kidney–liver transplants were excluded, the remaining 1502 patients were finally included, and their data were reviewed. The median duration of follow-up was 6.2 years.
Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. Results: A total of 68 patients (4.5%) developed PCP after transplantation. After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Additionally, both univariable and multivariable analyses showed a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31– 8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012), respectively. Also, the PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 [1.14–8.26]); P = 0.027).
The PCP-positive group had higher hazard ratios of graft failure [adjusted hazard ratio (HR), 3.1 (1.14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68–32.80); P < 0.001] than the PCP-negative group. All-cause mortality was higher in the PCP-positive group than in the PCP-negative group. However, the PCP event was not related with the subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody-mediated rejection and interstitial fibrosis and tubular atrophy
The article concludes that PJP is a significant risk for kidney transplant recipients and can impact transplant outcomes. The development of PJP was associated with a higher incidence of acute rejection, delayed graft function, and longer hospital stays. The use of prophylactic medications to prevent PJP is an effective strategy to improve transplant outcomes and reduce the risk of infection and improve transplant outcomes.
Level 3 evidence: a retrospective analysis.
Thank you
Please summarise this article.
Introduction:
Exclusion criteria: patients less than 18 yrs of age, and those receiving other organ with kidney transplant.
Defintions:
Methods and outcomes:
Primary outcomes:
Death censored graft failure- return to dialysis, or kidney retransplantation.
Secondary outcomes:
All – cause mortality, based on data obtained from the National Database of Statistics Korea, all followed until graft failure or till March;2018.
Statistical analysis:
Results:
Risk factors for PCP infection were:
First year post transplant (79.4% of affected cases)
Difference among PCP+/PCP- patients were more significant in males, being on preemptive transplants > peritoneal dialysis > hemodialysis (NOT the duration on dialysis), ABO incompatible, induction with basilximab, and CMV positivity.
The results based on outcomes:
Weakness:
Strength:
Conclusion:
The study clearly identifies the risk factors for PCP infection, and the protective effect of PCP prophylaxis.
The study showed that PCP+ has higher mortality, and may be a non-immune related graft failure.
What is the level of evidence provided by this article?
The level of evidence is II, retrospective cohort exposed to PCP as a risk factor, and looking for outcomes.
Thank you
2.results,
level of evidenc 3 (retrospective obserivational study).
Thank you
Please summarise this article.
Aim of the study : This article examines the impact of pneumocystis jirovecii pneumonia (PCP) on kidney transplant outcome.
Introduction :
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts, and its incidence varies from 0.6 to 14% among kidney transplant recipients without prophylaxis. Several studies have investigated the relationship between PCP and mortality, but the effect of PCP on graft rejection and overall graft outcomes has been less-well-explored. Certain infections such as cyto-megalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period, which is a meaningful clinical issue.
Methods and result :
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
Results: Showed that 68 patients (4.5%) developed PCP after transplantation, with positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis being risk factors. The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group, but the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings.
With the continued development of immunosuppressive regimens in the past decade, death-censored graft failures have gradually decreased in kidney transplant recipients.
.
Conclusion :
PCP is an important factor in relation to the risk of death and graft failure in kidney transplant recipients so appropriate infection prevention and treatment regimens need to be implemented to improve patient and graft survival outcomes which is expected to be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
.
Limitation of the study
– What is the level of evidence provided by this article?
-Level 3 ( observational retrospective cohort study)
Thank you
SUMMARY
The incidence of P. jirovecii pneumonia (PJP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy. In this study impact of PJP on kidney transplant outcomes, including graft failure and rejection were evaluated.
This is a retrospective observational study of total 1827 patients who had kidney transplantation and simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded. After a propensity score matching was performed, the graft and survival outcomes were compared between PJP-negative and PJP-positive groups with median duration of follow-up was 6.2 years.
Results
The infection rate was 6.8 cases per 1000 person-years.
Median time to the development of PJP was 5.2 months.
79.4% of cases developed during the first year after transplantation.
Non-use of oral prophylactic antibiotics were associated with an increased risk of PJP.
13.2% patients among PJP-positive recipients developed death-censored graft failure and they had a higher risk of death censored graft failure than the PJP negative recipients.
Increase risk of graft failure was occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs.
All-cause mortality was higher in the PJP-positive group.
Acute respiratory distress syndrome was the most common cause of death related with PJP.
Conclusion-PJP significantly increases both the risks of mortality and graft failure.
Limitation
Observational retrospective study.
Shorter prophylaxis time then recommended.
Level of evidence is 3 retrospective observational study
Thank you
Summary of the article
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
This is a retrospective observational study, analyzed 1502 KTRs at Seoul National University Hospital between 2000 and 2017 where the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. The study aimed at answering the question: Could PCP be implemented to address subsequent immunological complications?.
Pneumocystis jirovecii in KTR:
1. Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocom- promized hosts.
2. The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortal- ity of up to 50% despite aggressive antibiotic therapy.
3. Certain infections such as CMV and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
Results and Discussion
Results:
1. CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
2. Male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
3. Pre-transplant dialysis was newly identified as a protective factor of PCP (Uremic condition is linked to altered immunological responses).
4. The study’s analyses showed a significant relationship between PCP and graft failure.
5. The PCP-positive recipients had a higher risk of death- censored graft failure than the PCP-negative recipients.
6. No difference between PCP-positive and negative groups regarding the risk of subsequent occurrence of rejection, de novo DSAs, interstitial fibrosis and tubular atrophy.
7. All-cause mortality and mortality rate were higher in the PCP-positive group. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion:
1. Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
2. Previous studies have shown that CMV infection increases the risk of PCP which might be explained by modification of host immune response by CMV that alters the T cell response and aggravate pulmonary impairment during PCP activation.
3. PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations(overall graft failure).
4. The proinflammatory cytokines such as IL-1, IL-6, and IL-8 are known to be upregulated in patients with PCP and may also induce allograft injury.
Limitations of the study
1. It is a retrospective study making it difficult to demonstrate cause and effect definitively.
2. The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation and might increase overall risk of PCP in study subjects.
3. The present observational study design could not determine the mechanisms underlying the risk and sub- sequent effect of PCP.
Strengths of the study
1. The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
The level of evidence provided by this article:
This is a retrospective study with level of evidence grade 3.
Thank you
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in KTR.
Pneumocystis jirovecii is an opportunistic infection affects immunocom-promized patients .
It occurs in atound 0.6 to 14% among of KTR with high mortality rates of up to 50%.
Its long term effect on graft survival is still unclear.
This is a retrospective observational study on 1502 KTR comparing graft and survival outcomes between PCP-negative and PCP-positive groups.
*Methods
– The study design was approved by the institutional review board of Seoul National University Hospital
-1502 KTR from January 2000 to December 2017.
*Data collection
-Age, gender, height, weight, and body mass index.
– prior history of transplantation, the type and duration of dialysis, past medical history.
-ABO compatibility and the number of HLA mismatches, Immunosuppressive therapy including induction .
-PCP infection determined by CT findings, positive PCR, direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
-Initial use of prophylactic antibiotics with trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
-primary outcome was death-censored graft failure, secondary outcome was all-cause mortality.
-Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter.
-Additional kidney biopsies were done if indicated according to graft function with monitoring if DSA.
*Results
-4.5% of patients had PCP after kidney transplantation,79.4% of cases developed in the first year after transplantation.
-CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
-13.2% of PCP-positive patients developed death-censored graft failure.
-PCP-positive recipients had a higher risk of death-censored graft failure than the PCP-negative recipients.
-11-patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and negative groups, respectively.
-The PCP-positive group had a higher risk of mortality, 81.8% of deaths occurred within 3 months after the occurrence of PCP due to cute respiratory distress syndrome related with PCP.
*Discussion
-Long term effect of PCP on allografts needs more studies and weather this long term effect is related to the infection alone or with chronic inflammatory process and other unknown mechanisms is still unclear.
-Current study showed that male sex and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
-CMV infection affects the T cell ,which is important factor affecting the vulnerability to and resolution of PCP, and alteration of the T cells and its aging by CMV might aggravate pulmonary impairment during PCP.
-Pre-transplant dialysis was newly identified as a protective factor of PCP.
-PCP did not increase the risk of any rejection after infection, so a non-immunological factors may be the cause underlying the observations.
-Mortality risk was higher in patients with PCP and the rIsk is highest within the first 3 months of infection therefore
prophylaxis against PCP may be strongly recommended for 3–6 months after transplantation.
But still definitive guidelines on the duration and dosage of PCP prophylaxis are not available
*Limitations
– a retrospective study, making it difficult to demonstrate cause and effect definitively.
-prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (3–6 months)
-The duration of antibiotic prophylaxis might differ between centers.
-present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
What is the level of evidence provided by this article?
Retrospective study level of evidence III.
Thank you
Please summarise this article.
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in kidney transplant recipients. Acute phase toxicity in patients with PCP is well established , but there is a lack of data on the effects of PCP on long-term graft outcome. Pneumocystis jirovecii is an opportunistic pathogen which causes pulmonary infection in immunocompromized with incidence from 0.6 to 14% among kidney transplant recipients without prophylaxis. The mortality in spite of aggressive antibiotic treatment is 50%. The study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methodology
It was a retrospective observational study with 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. The graft survival & outcomes were compared between PCP-negative and PCP-positive groups. Those under age 18 years and those receiving combined kidney and pancreas transplant were excluded. Thus total no was 1502.
Protocol biopsies at Day 0. 10 and 365
Results
Follow up time 6 years and 2 months
A total of 68 patients experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months & 79.4% of cases developed during the first year after transplantation.
CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
There was a significant relationship between PCP and graft failure, with HRs of 3.34 and 3.33respectively.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
Discussion
The use of ATG and the presence of CMV infection increases the risk of PCP
The occurrence of PCP itself did not affect the risk of following development of acute
rejection and de novo DSA production
Conclusion
· PCP is associated with higher risk of graft loss and mortality.
· Risk of PCP is high in male sex and with non use of antibiotics
· More trials needed on the use of prophylaxis in kidney transplant recipients
What is the level of evidence provided by this article?
Level 111
Thank you
Introduction :
Pneumocystis jirovecii is an opportunistic pathogen that causes serious lung infections in immunocompromised individuals. Incidence of P. jirovecii pneumonia (PCP) ranges from 0.6 to 14% in unpreventive kidney transplant recipients despite aggressive antibiotics. It has a mortality rate of up to 50%.
Methods:
A retrospective observational study was conducted on 1,502 adult kidney transplant patients at Seoul National University Hospital from 2000 to 2017. PCP positive group.
Results:
Average follow-up was 6. 2 years (interquartile range 3.0-9.6 years; maximum 18.3 years)
Of 1502 patients, 68 (4.5%) had pneumocystis pneumonia after kidney transplant, with an infection rate of 6.8 cases per 1000 person-years Median time to onset of PCP was 5.2 months (interquartile range 3.9-10.0 months), 79.4% of cases occurred within 1 year of transplantation
Significant difference between PCP-positive and negative patients Gender; Regarding pre-transplant dialysis type, ABO incompatibility, desensitization therapy, induction therapy, hypertension and CMV positivity. Death-screened graft failure occurred in 9 (13.2%) of 68 PCP-positive recipients. ACox multivariate analysis found that positive cytomegalovirus and lack of early oral antibiotic prophylaxis were risk factors for PCP after transplantation. There was a higher hazard ratio for transplant rejection in the PCP-positive group [adjusted hazard ratio (HR), 3.1 (1.1). 14–8.26); P = 0.027] and mortality [adjusted HR, 11.0 (3.68-32.0). 80); P<0.001] than the PCP negative group. However, the PCP events were not associated with subsequent development of de novo donor-specific antibodies or pathological changes such as T-cell or antibody-mediated rejection, interstitial fibrosis, and tubular atrophy
Conclusion:
PCP has long been a risk factor. -Term transplant rejection and mortality with or without rejection. Therefore, proper prevention and treatment are necessary to avoid the side effects of PCP transplantation.
I like your detailed summary and analysis.
Please summarise this article.
1- 68 patients (4.5 %) developed an acute PJP pneumonia. there were 2 identifiable risk factors for having this disease. the 1st was +ve CMV status and the 2nd was lack of oral antibiotic prophylaxis.
2- graft failure was more in the +ve group with an adjusted hazard ratio of 3.1, as compared with the -ve group.
3- mortality was more in the +ve group with an adjusted hazard ratio of 11, as compared with the -ve group.
3- there was no relation between PJP and subsequent development of de novo DSA or pathologic changes as T-cell mediated rejection, interstitial fibrosis or tubular atrophy.
1- PJP is a risk factor for long-term graft failure and mortality that are independent of rejection.
2- appropriate prophylaxis and treatment are still necessary for PJP
What is the level of evidence provided by this article?
I like your detailed summary and analysis.
Why would you label this as level 3?
Please use bold or underline for headings and sub-headings to make it easier to read.
Introduction
In patients with a functional graft, infection is the second leading cause of death after CVS illness. Data on the immunological effects of particular infectious illnesses in transplant recipients is scarce. Hence, more research on infectious posttransplant occurrences is required to enhance survival rates. Pneumocystis jirovecii is an opportunistic pathogen that causes severe lung infections in immunocompromised patients, with a 50% mortality risk in those who do not receive prophylactic antibiotics and even after vigorous antibiotic therapy. In this study, the effects of PCP on kidney transplant outcomes, such as graft failure and rejection, were assessed.
Methods
The 1502 adult patients who received kidney transplants at Seoul National University Hospital between 2000 and 2017 were the subject of this retrospective observational study. Following the use of propensity score matching, the graft and survival results of the PCP-negative and PCP-positive groups were compared with a median follow-up of 6.2 years.
Results
Out of 1502 patients, 68 (4.5%) developed PCP after KT, with a 6.8 case/1000 person-year infection rate. The average time it took for PCP to manifest was 5.2 months, and 79.4% of cases appeared within the first year.
Regarding gender, pre-transplant type of dialysis, ABO-i, desensitization therapy, induction regimen, HTN, and CMV positivity, there were significant variations between PCP-positive and -negative patients. CMV positive and not using oral prophylactic antibiotics were linked to an elevated risk of PCP when several variables were adjusted for.
13.12% of the 68 PCP-positive recipients experienced death-censored transplant failure. Compared to the PCP-negative group, the PCP-positive group showed greater graft failure hazard ratios.
All of the patients were men, and none of them had ever used prophylactic antibiotics following a transplant. Eight out of nine patients (88.9%) developed acute kidney injury throughout the hospitalization period, and four of them (50%) did not have their graft functions fully recovered at release despite responding well to PCP.
Limitations
The first limitation of the study was that it was a retrospective study.
Second, the present definition of prophylactic antibiotics, one month, was shorter than the recommended by guidelines.
Level of evidence
Level 3: Observational retrospective cohort study
I like your detailed summary, limitations of study and analysis.
Why would you label this as level 3?Is it a retrospective cohort or a case-control study?
Thank you Professor for your comment.
The provided study is a retrospective cohort study looking for risk factors and the outcome of interest, so maybe level of evidence between II and III. I am confused because level of II implies that the study is prospective and not retrospective.
Long term effects of PCP infection on the graft outcome
Summary
· Infections are 2nd cause of mortality among adult transplant recipients after cardiovascular causes of death.
· PCP is a well-known cause of post-transplant morbidity and mortality in kidney transplantation.
· Risk factors as strong IS use, lack of chemoprophylaxis and concomitant CMV infection.
· Dialysis and improvement of uremic state can decrease the risk of post-transplant PCP infection, but prolonged duration can worsen the outcome.
· The current study aimed to Compare between PCP positive and negative cases regarding long term graft survival (based on allograft biopsy done every year to detect TCMR, ABMR and IFTA).
· During acute infection, it has deleterious effects on the graft that can be related to immunological and none immunological factors, in addition to the upregulation of cytokines.
· However, the long-term outcome needs to be evaluated. PCP was associated with worse graft outcome (but not explained by more rejection episodes or increasing IFTA).
· PCP was diagnosed by CT chest and identification of the organism by IF staining and PCR.
· KDIGO recommends standard prophylaxis for 3-6 months against PCP with SMX-TMP.
· Points of weakness: retrospective, prophylactic chemotherapy was given for only one moth (while standard recommendations is to give 3-6 months)
· Points of strength: large number of cases,
Level of evidence: retrospective cohort (level III)
I like your detailed summary, weaknesses and strengths of study and analysis.
Why would you label this as level 3?Is it a retrospective cohort or a case-control study?Typing whole sentence in bold or capitals equals to shouting !
Thanks dear professor
It is retrospective cohort , level of evidence is II.
Sorry , I will take care of bold and capital sentences in the next time
Impact of Pneumocystis jirovecii pneumonia
on kidney transplant outcome.
Introduction:
Still cardiovascular diseases is the most common cause of death post kidney transplant with functioning graft, followed by infection, one of these infection is Pneumocystis jirovecii which is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts, the incidence of PJP is increasing up to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy, as well known cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early post-transplant period and in this study they evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods.
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups with median duration of follow-up was 6.2 years.
Results:
-The infection rate was 6.8 cases per 1000 person-years and the median time to the development of PCP was 5.2 months with 79.4% of cases developed during the first year after transplantation.
-CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
-9 (13.2%) patients among 68 PCP-positive recipients developed death-censored graft failure and the PCP-positive recipients had a higher risk of death censored graft failure than the PCP negative recipients.
– The cause of the elevated risk of graft failure are occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs.
– All-cause mortality was higher in the PCP-positive group than in the PCP-negative group and the most common cause of death was acute respiratory distress syndrome related with PCP.
Conclusion.
Male gender, positivity for CMV, and non-use of oral prophylactic antibiotics are considered risk factors of PCP in the kidney transplant cases and PCP significantly increases both the risks of mortality and graft failure.
Level of evidence:3 (Retrospective observational study).
I like your detailed summary, and analysis.
Why would you label this as level 3?
Is it a retrospective cohort or a case-control study?
A retrospective study conducted in S. Korea between years 2000 and 2017 to verify the mortality and allograft dysfunction incidence associated with PJP infection post transplantation. 1502 transplant patients had their transplant performed in Seoul university hospital, were surveyed for post-transplant PJP infection incidence and allograft and patients’ survival were compared between PJP positive and PJP negative patients.
Study conclusions:
Patients’ mortality was higher in PJP infected compared to Non PJP infected. The increasing mortality rate was attributed to the fungal infection itself or to other superadded infections.
Allograft survival was compromised in PJP infected patients, however, there was no increased incidence of rejection or production of DSAs post infection, speculating that its non-relevant to immunological derangement and heightened risk of rejection.
Non immunological factors for allograft failure were suggested by this study, as PJP infection is linked to acute kidney injury with lingering progressive deterioration of allograft function consequently. Similarly, inflammatory cytokines might be crucially inflicting allograft function, such as IL1, IL6 and IL8 are augmented by PJP infection causing inflammation and fibrosis on long term course post PJP infection.
Risk factors:
CMV co-infection was main risk factor for PJP infection, owing to its role in modulating and suppressing cell mediated immunity and C4D lymphocytes in particular predispose to fungal infection of PJP.
Other risk factor was the lack of prophylactic anti-PJP, which is against the general recommendation of CDC to have 3-6 months prophylactic protocol.
Limitation of the study:
1] Observational retrospective study.
2] prophylaxis protocol considered during the study period was for 1 month, falling shorter than the recommendation of 3-6 months, portending higher risk of PJP.
3] The mechanism and risk of PJP infection can’t be assessed properly given the retrospective nature of the study.
Level of evidence 3
I like your detailed summary, limitations of study and analysis.
Why would you label this as level 3?
Introduction
Immunosuppression have been developed. However, infections have been considered as an important factor (second cause ) of death after renal transplantation.
○ PCP incidence is about (0.6 – 14 ) %
○The aim of this study is to evaluate the relation between PCP and renal transplantation outcomes (especially on the graft failure and graft rejection)
Methods
○The study was in Seoul National University Hospital.
○This is a retrospective observational study
○The total number of patients was 1502
○It was performed between 2000- 2017
Criteria of excluding
○Age less than 18 years
○Pancreatic and liver co-transplantation
○
Primary outcome : Death censored graft failure
Secondary outcome: mortality
○The protocol of graft biopsies was performed to identify: (acute T cell mediated rejection- antibodies mediated rejection- interstitial fibrosis and tubular atrophy)
Results
○Median duration of the following up is 6.2 years
○68 patients of 1502 (4.5%) had PCP
○The median time to PCP development was 5.2 Months. But 79.4% was in the first year.
○Risk factors for PCP occurrence after kidney transplantation
GRAFT FAILURE
○9of 68 patient (positive PCP) 13.2% have graft failure (univariable and multivariable analysis showed significant relationship between PCP and graft failure.
○From those who developed graft failure (9), eight of them had AKI
Therefore, graft failure might not be attributed to the immunological factors but might be related to non immunological factors as AKI
○On the other hand, the occurrence of PCP itself did not affect the risk of following development of acute rejection- De novo DSA.
MORTALITY
○mortality was higher 11(16%) in PCP POS compared to (11%) IN PCP neg.
81% of them was happened during the first 3 months.
LIMITATIONS
Strengths
Recommendations
Prophylaxis for PCP is recommended but the duration still controversial.
Level III
level 3
I like your detailed summary, limitations and analysis.
Why would you label this as level 3?
Please summarise this article.
-Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts .
-Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts .
– The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy .
-It is retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017. Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas
or kidney–liver transplants (n = 65) were excluded. The remaining 1502 patients were finally included and their data were reviewed.
-The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
-The occurrence of PCP increased the risk of long-term graft
Failure.
-Intensive treatment and prophylaxis of PCP is recommended after transplantation.
-Pre-transplant dialysis was newly identified as a protective factor of PCP. Uremic condition is linked to altered immunological responses.
-The study showed that PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
– Mortality risk was elevated in patients with PCP.
-According to the KDIGO it is recommended that all recipients receive prophylaxis against PCP for 3–6months after transplantation .
Limitation :
-it was a retrospective study, making it difficult to demonstrate cause and effect definitively.
-The duration of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation .
-The study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
What is the level of evidence provided by this article?
Level 3
I like your detailed summary, limitations of srudy and analysis.
Why would you label this as level 3?
Please use bold or underline for headings and sub-headings to make it easier to read.
summarise of Impact of Pneumocystis jirovecii pneumonia
on kidney transplant outcome
Introduction
· Infection is the second cause of death after CVS disease in patients with a functioning graft.
· There is little data on immunological outcomes after specific infectious diseases in the transplant recipient.
· Further studies of posttransplant infectious events are therefore needed to improve survival outcomes.
· Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized patients.
· 0.6 -14% incidence of pneumonia in p.j.
· 50% mortality rate in kidney transplant recipients without prophylaxis and even after aggressive antibiotics therapy.
· This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
· Study design retrospective observational study included 1827 patients who had a kidney transplants at Seoul Natuval University Hospital from jan2000 to dec 2017.
· Transplant outcome: the primary outcome was death-censored graft failure defined as a return to dialysis or kidney re-transplantation. And secondary outcome was all-cause mortality.
· Results:
· There are significant differences between PCP -positive and negative patients with response to gender, type of pretransplant dialysis ,ABOI transplant, desensitization therapy, induction regimen, HTN and CMV positivity and non-use oral prophylaxis antibiotics were associated with an increased risk of PCP.
· PCP and transplant outcome: among 68 PCP-positive 13.2% of patients develop death-censored graft failure. There is a significant relation between PCP and graft failure with HR 3.34 and 3.33 % respectively.
· The result suggests that different graft failure rates might not be attributed to the conventional immunological transplant episodes but might be related to non immunological factors such as concurrent acute kidney injury.
· The most common cause of death was acute respiratory distress syndrome related to PCP.
· Discussion :
· PCP is relatively common after kidney transplantation, its clinical implication especially in relation to graft outcome has not been evaluated.
· The result of the study found that male gender and CMV positive were risk factors associated with PCP and the use of oral prophylactic antibiotics seem to prevent the risk of PCP.
· CMV infection increases the risk of PCP as might modify the host immune response leading to immunosuppression.
· Pre-transplant dialysis was newly identified as a protective factor of PCP,.however term pre-transplant dialysis negatively affect host immune status .
· Limitation of the study:
· 1-Retrospective study making it difficult to demonstrate the cause and effect definitively.
· 2-definition of prophylactic antibiotics 1 month which was shorter than the guidelines recommendation (3-6)month.
· 3-observational study design could not determine the mechanism underlining the risk and subsequent effect of PCP.
· Conclusion:
· Risk factors of PCP in kidney transplant cases with the male gender. positively for CMV, and non-use of oral prophylactic antibiotics.
· PCP significantly increases both the risk of mortality and graft failure.
evidence level 3
I like your detailed summary, limitations of the study and analysis.
Why would you label this as level 3?
Background
● Infection is an important risk factor of death in kidney transplant recipients
● Pneumocystis jirovecii is an opportunistic pathogen causes severe pulmonary infection in immunocopromized hosts
● The incidence is 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy
● This study evaluates the impact of PCP on kidney transplant outcomes, including graft failure and rejectionm
Methods
● A retrospective observational study
● 1827 kidney recipients at Seoul National University Hospital
● From January 2000 to December 2017. ● Excluded Patients :
☆ under 18 years old
☆ Simultaneous kidney–pancreas or kidney–liver transplants
● 1502 patients were included
Data collection and definitions
● Data from the kidney transplant recipients were collected from the electronic medical records.
● PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomog-raphy combined with PCP positivity in sputum or bronchoalveolar lavage fluid.
Transplant outcomes
● The primary outcome was death-censored graft failure
● The secondary outcome was all-cause
mortality
Results
● The median duration of follow-up is 6.2 years (3.0–9.6 years )
● 4.5% experienced PCP after Kidney Tx
● The median time to the development of PCP was 5.2 months
● 79.4% developed during the first year after transplantation.
● Factors associated with an increased risk of PCP :
☆ CMV positivity
☆ The non-use of oral prophylactic
☆ Male gender
● 13.2% of patients with positive PCR developed death-censored graft failure.
● 16.2% , 11.0% and 28.6% died in the PCP-positive , negative groups,and PCP-positive with concurrent infection respectively.
● 81.8% died within 3 months after the occurrence of PCP.
● The most common cause of death was acute respiratory distress syndrome
● The occurrence of PCP increased the risk of long-term graft failure and mortality due to Non-immunological factors ( AKI and proinflammatory cytokines ) other than immunological transplant episodes
● Pre-transplant dialysis but not long term dialysis was identified as a protective factor of PCP due to altered immunological responses by Uremic condition
● all recipients receive prophylaxis against PCP for 3–6 months after transplantation
● limitations of study :
☆ A retrospective study
☆ prophylactic antibiotics duration was shorter which could alter the risk of PCP and transplant outcomes.
☆ Mechanisms underlying the risk and sub-sequent effect of PCP could not determine by this study design
Level evidence : 3
I like your detailed summary and analysis.
Why would you label this as level 3?
Please use bold or underline for headings and sub-headings to make it easier to read.
Please summarise this article.
# The objective of the study:
Is to determined the effect of PCP on allograft transplant outcomes involving the graft failure and rejection.
# Introduction:
*The common cause of mortality in recipient with functioning kidney is CVD, followed by Infection.
*There is a few information on immunologic outcomes following specific infectious disease in KTR, so more studies in this field are needed.
*PCP is an opportunistic pathogen that lead to severe pulmonary infection in immunocompromized
Patients.
*The rate of PCP varies between (0.6 to 14%) between KTR without prophylaxis, and the deaths is up to 50% in spite of heavy antibiotic therapy treatment.
# Method:
*This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
*After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
*Excluding criteria:
Patients below18 years old , who received kidney–pancreas or kidney–liver transplants .
# The result:
*Out of 1502 patients, 68 (4.5%) experienced PCP post KT, with an infection rate of 6.8 cases per 1000 person-years.
*The median time to the development of PCP was 5.2 months and 79.4% of cases developed during the first year.
*There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-i, desensitization therapy, induction regimen, HTN and CMV positivity.
* After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
*Between 68 PCP-positive recipients, (13.2%) developed death-censored graft failure.
* The PCP-positive group had higher hazard ratios of graft failure than the PCP-negative group.
*All the patients were male and had no history of prophylactic antibiotics usage after transplantation.
*During the admission period, 8 of 9 patients (88.9%) experienced acute kidney injury according to the KDIGO criteria, and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
# The limitation of the study:
*Retrospective study, making it difficult to demonstrate cause and effect definitively.
The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
*The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months),
*The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
# Conclusion:
*Risk of PCP is aggravated in the KT cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
*PCP significantly increases both the risks of mortality and graft failure.
* Prophylaxis may be needed to prevent PCP and subsequent graft failure.
*The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
What is the level of evidence provided by this article?
*Level (3)
Well done
Tkank you very much
Introductions:
Infection is second leasing cause of deaths postbkidney trajsplant.
PCP cause increases mortality in 50percent of infected posttransplant patient.
The study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods Study design and subjects:
retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture.
Transplant outcomes
The primary outcome was death-censored graft failure.
The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018.
Data collected for ABMR and CMR.
Results Baseline characteristics and risk factor of PCP
After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP .
PCP and transplant outcomes :
a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31– 8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012), respectively.
the PCP-positive recipients had a higher risk of deathcensored graft failure than the PCP-negative recipients .
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group.
The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion :
male gender and CMV positivity were risk fir PCP.
use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
Pre-transplant dialysis was newly identified as a protective factor of PCP.
Limitation of the study:
First, it was a retrospective study, making .
Second, the current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months).
Level of evidence :3.
Thankyou.
Well done
Without prophylaxis, kidney transplant recipients had a P. jirovecii pneumonia (PCP) incidence ranging from 0.6 to 14%, with a mortality of up to 50% despite rigorous antibiotic therapy.
In total, 1827 individuals underwent kidney transplantation at Seoul National University Hospital between January 2000 and December 2017 were included in this retrospective observational analysis. Patients under the age of 18 (n = 260) and those who had simultaneous kidney, pancreas, or liver transplants (n = 65) were both disqualified.
Both univariable and multivariable analyses revealed a substantial association between PCP and graft failure among the 68 PCP-positive recipients, where 9 (13.2%) patients experienced death-censored graft failure.
Although other immunological findings such as interstitial fibrosis, tubular atrophy, and de novo DSA as well as acute T cell-mediated and antibody-mediated rejection episodes were also adjusted, the PCP-positive recipients still had a higher risk of death-censored graft failure than the PCP-negative recipients.
The findings imply that graft failure rates may not be connected to immunological transplant episodes in the traditional sense, but rather to non-immunological variables such as concomitant acute renal damage.
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics. PCP significantly increases both the risks of mortality and graft failure.
Accordingly, robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
A retrospective observational study (level III)
Thankyou.
In KTRs, Infection is the second most common cause of death with functioning graft after cardiovascular disease.
P. jirovecii pneumonia (PCP) one of the opportunistic infection associated with high mortality rate despite treatment. Certain infections increased risk of graft rejection. The effect of PCP on graft function is not well studies.
Aim of the study:
Evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Transplant outcomes
Primary outcome : death-censored graft failure defined as a return to dialysis or re-transplantation.
Secondary outcome: all-cause of mortality.
Methods
Study design Retrospective observational study.
Study period: from January 2000 to December 2017.
Follow up: All patients were followed until graft failure or March 2018
Included: total 1827 KTRs at Seoul National University Hospital.
Exclusion: Patients < 18 years old (n = 260) or patients received simultaneous kidney–pancreas or kidney–liver transplants (n = 65).
Data collection from EMR.
Results for ABO, HLA typing Immunosuppressive therapy were collected.
PCP was defined; suspicious of PCP radiologically on chest CT with PCP positivity on PCR or direct immunofluorescence stain of sputum or BAL.
Initial use of oral prophylactic antibiotics; defined as a prescription of TMP/SMX for > 4 weeks during the first month after KT.
There were no cases with pentamidine or atovaquon for prophylaxis.
CMV positivity; defined as > 20 copies/ml on PCR or positive culture
Protocol biopsies: done at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter.
Additional biopsies: if graft function is deteriorated, or signs of rejection.
De novo DSA: as any newly developed anti-HLA class I or II antibody.
Propensity score matching was performed to account for the imbalance in baseline characteristics between the PCP-positive and -negative groups.
Results:
-1502 patients included and followed for median of 6.2 years
-PCP infection occurred in 68 (4.5%) KTRs.
-Multivariable Cox analysis showed: CMV- positivity and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
-Both univariable and multivariable analyses showed a significant relationship of PCP with graft failure HR of 3.1
– No difference in risk of development of de novo DSA or pathological finding of rejection between PCP-positive and –negative groups
– PCP-positive patients had concurrent AKI and half of them did not achieve the recovery which might leave the grafts with non-immunological damages.
-All-cause mortality was higher in the PCP-positive group HR of 11.0than in the PCP-negative group
81.8% died within 3 months after the occurrence of PCP.
-The most common cause of death was ARDS related with PCP.
Conclusions:
PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
Limitations:
– Retrospective nature of the study, difficult to demonstrate cause and effect definitively.
– The overall risk of PCP might be higher in the study as duration of prophylactic antibiotics was 1 month, which was shorter than the recommendations (3–6 months)
Strength:
-Good follow up period.
Level of evidence:
Level 3; Observational retrospective cohort study ( started with risk factor PCP positive or negative then looked at outcomes (mortality, graft survival)
Exellent analytical summary.
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome:
This article is retrospective observational study were kidney transplant patients collected from Seoul National University Hospital from January 2000 to December 2017. This article focus on impact of Pneumocystis jirovecii is on solid organ transplant and it’s outcome.
Introduction:
Pneumocystis jirovecii is an ascomycetous fungus and an opportunistic pathogen that can cause morbidity and mortality and increase risk of rejection in immunocompromised patients with transplant.
Risk factors of PCP were there are differences in patients with positive PCP and negative patients; so there’s high risk of PCP in positive patients and those how not receive prophylactic treatment against PCP in respect to other co-morbidity. The maximum time for exposure of patients to infection is 5.5 months post kidney transplant.
The all PCP-positive recipients with graft failure are male and no history of receiving prophylactic antibiotics. Those patients has high risk of death.
PCP positive patients associated with occurrence of rejection, interstitial fibrosis and tubular atrophy and developing of de novo DSA. This study shows patients with CMV infection increase risk of PCP. Where CMV lead to alteration and impair T cell (CD4), function which are expose patients to PCP infection.
Pre- dialysis duration and uremic condition also expose to increase infection because impaired of immunological factors. Occurrence of PCP increase risk of graft failure; also other viral and bacterial infection increase risk of graft failure, however PCP infection itself is not lead rejection but immunological alteration expose patients to rejection. Another non-immunological pathways, infections may also induce allograft injury by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8.
Limitations of this study:
Well done,though your information of immunological direct implication mentioned twice is contradicting.
1. Please summarise this article.
Introduction: Pneumocystis jirovecii, an opportunistic fungal infection, causes pneumonia (PCP) in kidney transplant recipients, with incidence rates ranging from 0.6 to 14% and a mortality rate upto 50% despite treatment in patients without PCP prophylaxis. The effect of PCP on graft rejection and long-term graft results is not known.
Methods: The study conducted was a retrospective observational analysis of effect of PCP on graft rejection and failure in kidney transplant recipients. A total 1827 patients were included, out of which 325 were excluded with final review done for 1502 patients who underwent kidney transplant at Seoul National University Hospital from 2000 to 2017. The patients were divided into 2 groups: PCP-positive, and PCP-negative groups, and graft outcomes and patient survival were compared between them.
Results: 1502 patients were followed up for median time of 6.2 years. 68 out of the 1502 (4.5%) patients developed PCP. Median time to develop PCP was 5.9 months, with 79% developing PCP within first year. Risk factors for PCP included Cytomegalovirus (CMV) positivity, non-use of prophylactic antibiotics, and male gender. 13% of the PCP-positive group developed death censored graft failure (DCGF) pointing towards increased risk of graft failure (hazard ratio 3.1). All PCP-positive patients developing graft failure were males, had no history of PCP prophylaxis, and most had associated acute kidney injury (AKI) at time of admission. PCP-positive group had increased risk of mortality (hazard ratio 11) as compared to the PCP-negative group, and more than 80% died within 3 months of developing PCP. Protective factors for PCP included use of prophylactic antibiotics, and pre-transplant dialysis. There was no difference with respect to donor specific antibody (DSA) formation, acute rejection (suggesting non-immunological cause of graft failure) , or interstitial fibrosis and tubular atrophy between the 2 groups.
Limitations: Retrospective study, lack of clarity regarding duration of prophylactic treatment given, use of non-standardized definition of prophylactic antibiotics in the study (increasing risk of PCP),and inability to ascertain mechanisms underlying the risk and effects of PCP due to the observational design of the study.
To conclude, PCP in renal transplant recipients increases risk of graft loss and mortality, and hence adequate measures should be taken to prevent (by using oral prophylactic antibiotics) and aggressively treat PCP.
2. What is the level of evidence provided by this article?
The level of evidence is level 3: A retrospective case control study
Comprehensive ,exellent.
This is a retrospective observational study done inSeoul national center to detecte the effect of PCP on kidney graft survival and the rate of rejection if any .
This study done 1502 patient post RTX , this study was conducted from 2000 to 2007 data obtained from medical records , PCP was daignosed according to imaging and PCR .The aim of the study to know if there is diretc relation between PCP and rejection or survival rate like other CMV and B virus .
usually PCP is an oppertunistic infection with mortality rate of 50% post RTX with morbidity of 0.6 to 14 % .
THe study concolude that ,Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
▪︎PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
this article is level III retrospective study
Well done.
Background:
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromised hosts. The incidence of P. jirovecii pneumonia (PCP): 0.6 to 14% among kidney transplant recipients without prophylaxisMortality of up to 50% despite aggressive antibiotic therapy.This study evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Material and methods:
Retrospective observational study Analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups. Results:
Median follow-up: 6.2 years68 (4.5%) experienced PCP after kidney transplantationMedian time to develop PCP: 5.2 months79.4% of cases developed during the first year after transplantation.CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.Eleven patients (81.8%) died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.Discussion:
Male gender and CMV positivity were risk factors associated with PCPUse of oral prophylactic antibiotics prevented the risk of PCP.The occurrence of PCP increased the risk of long-term graft failureThis relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.PCP was associated with both graft failure and overall mortalityThat is why intensive treatment and prophylaxis is recommended after transplantation.Limitations :
Retrospective studyProphylaxis given only for 1 month which could be 3 to 6 months
Level of evidence: Level III (retrospective study)
Thankyou well done.
SUMMARY
Introduction
There has been a great improvement in graft survival in the last decades as a result of simultaneous development and improvement in immunosuppressive medication. However, the same could not be said of death that occurs with a functioning graft, and infections have been implication as part of the aetiological causes.
Pneumocystis Jirovechii is an opportunistic pathogen that could manifest with a severe form of respiratory infection, particularly in an immunocompromised host like post-kidney transplant recipients. Its incidence is 0.6% – 14% and with a mortality of about 50% if prophylaxis is not administered
Aim of the study
Method of the study
Transplant Outcome
Results
Limitations of the study
Strength of the study
Level of evidence
A retrospective case-control, Level III
Well done .
IT is an observational study.
Thank you prof Dawlat
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
This retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017 which evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Median duration of follow-up was 6.2 years (IQR, 3.0–9.6 years; maximum 18.3 years).
68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
Median time to the development of PCP was 5.2 months (IQR, 3.9–10.0 months)
79.4% of cases developed during the first year after transplantation.
Significant differences between PCP-positive and -negative patients with respect to
Gendertype of pre-transplant dialysis,ABO-incompatibility,desensitization therapy,induction regimenhypertensionCMV positivityPropensity score matching to mitigate the difference in baseline characteristics between the PCP-positive and -negative groups was done.
Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure
Both univariable and multivariable analyses showed a significant relationship between PCP and graft failure, with HRs of 3.34 (1.31–8.56) (P = 0.012) and 3.33 (1.30–8.53) (P = 0.012)
PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients despite acute TCMR and ABMR or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted.
PCP-positive patients with graft failure were all the patients were male and had no history of prophylactic antibiotics usage after transplantation.
8 of 9 patients (88.9%) experienced AKI according to the KDIGO and 4 of them (50%) did not have recovered their graft functions at discharge despite the recovery from PCP.
The study evaluated the effect of PCP on the risk of subsequent occurrence of rejection, interstitial fibrosis and tubular atrophy, and de novo DSAs and these outcomes did not differ between PCP-positive and –negative groups
Different graft failure rates might not be attributable to the conventional immunological transplant episodes, but might be related with non-immunological factors such as concurrent AKI
11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and PCP-negative groups
28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%)
All-cause mortality was higher in the PCP-positive group,adjusted HR, 10.99
Limitation
retrospective studydefinition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation.duration of antibiotic prophylaxis might differ between centerscould not determine the mechanisms underlying the risk and subsequent effect of PCPConclusion
Risk of PCP is increased in the KT with male gender, positivity for CMV, and non-use of oral prophylactic antibioticsPCP increases both the risks of mortality and graft failureprophylaxis may be needed to prevent PCP and subsequent graft failure.
What is the level of evidence provided by this article?
A retrospective observational study (level III)
I like your detailed summary and analysis.
¤ Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
__________________________
▪︎This study has evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
◇ Background:
▪︎Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts. ▪︎Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immuno- compromized hosts .
▪︎The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
▪︎While the acute phase toxicity in patients with PCP is well-characterized, there is a lack of data on the effects of PCP on long-term graft outcome.
◇ Method:
▪︎ This a retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017.
▪︎ After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
◇ Results:
▪︎A total of 68 patients (4.5%) developed PCP after transplantation.
▪︎The multivariable Cox analysis showed
that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
▪︎ The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group. However, the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
◇ Limitation of he study:
1. A retrospective study, making it difficult to demonstrate cause and effect definitively.
2. The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects
3. The duration of antibiotic prophylaxis (i.e., more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes.
3. The present observational study design could not
determine the mechanisms underlying the risk and subsequent effect of PCP
◇ Strength of the study:
1. Informative data.
2. The study achieved its primary purpose:
a. By demonstrating the relationship
between PCP and transplant outcome
b. On the relationship between PCP and
transplant outcomes.
◇ Conclusion
▪︎Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
▪︎PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP
▪︎The present study will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients
¤ Level of evidence:
Level III (a retrospective study)
Why is not a case control study?
▪︎This is a retrospective observational cohort study becaus, it started with risk factor ( PCP positive or negative), then study the outcomes (mortality and graft survival).
▪︎While retrospective cohort studies try to compare the risk of developing a disease to some already known exposure factors, a case-control study will try to determine the possible exposure factors after a known disease incidence.
Please summarise this article.
Infection is an important factor in relation to the risk of death in kidney transplant recipients, the second most common cause of death
The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50%
Methods Study design and subjects
retrospective observational study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded
the remaining 1502 patients their data were reviewed.
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records
Demographic characteristics including age, gender, height, weight, and body mass index were collected.
Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes
Results for both recipient and donor ABO blood groups (ABO) and human leukocyte antigen (HLA) typing were collected to evaluate ABO compatibility and the number of HLA mismatches.
Immunosuppressive therapy was determined, including induction therapy with basiliximab or anti-thymocyte globulin, and calcineurin inhibitors for maintenance therapy. A combination of steroids, mycophenolic acid, and calcineurin inhibitors
PCP was defined as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
Initial use of oral prophylactic antibiotics was defined as a prescription of trimethoprim/sulfamethoxazole for more than 4 weeks during the first month after kidney transplantation.
There were no cases with pentamidin or atovaquon for prophylaxis. CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infectionTransplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
The secondary outcome was all-cause mortality, based on data obtained from the National Database of Statistics Korea. All patients were followed until graft failure or March 2018.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were also collected.
Protocol biopsies were performed at zero-time (postreperfusion), on the 10th day and 1 year after transplantation, and every year thereafter.
Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years. The median time to the development of PCP was 5.2 months (interquartile range, 3.9– 10.0 months), and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity. After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP
PCP positive (n = 68)
Hemodialysis 47.1%
ABO-incompatible 19.1%
Tacrolimus 85.3%
Basliximab 892.6%
Antithymocyte globulin 0%
Oral prophylactic antibiotics 10.3%
Positivity for CMV 60.3%
Acute T cell-mediated rejection 61.8%
Acute antibody-mediated rejection 11.8%
What is the level of evidence provided by this article?
retrospective cohort study observational
level of evidence 3
Why is not a case control study?
yes .noted
it is a case control study that establish a correlation between exposures and outcomes, but cannot establish causation.
PCP negative group
PCP positive group
Background
With the continued development of immunosuppressive regimens in the past decade, death-censored graft failures have gradually decreased in recipients of both living and deceased kidney recipients.
More information on the causes of mortality unrelated to graft failure is needed to further improve the survival of transplant recipients.
Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Despite its clinical implication of these infectious diseases, there is little data on immunologic outcomes after specific infectious disease in transplant recipients.
Several studies have investigated the relationship between PCP and mortality , but the effect of PCP on graft rejection and overall graft outcomes has been less-well explored
Certain infections such as cytomegalovirus (CMV) and BK virus have demonstrated relationships with acute rejection during the early posttransplant period.
We evaluated the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Study design and subjects
The study design was approved by the institutional review board of Seoul National University Hospital
The study design was approved by the institutional review board of Seoul National University Hospital and complied with the Declaration of Helsinki.
1805-173-948) and complied with the Declaration of Helsinki
This retrospective observational study included total 1827 patients who had kidney transplantation.
Seoul National University Hospital from January 2000 to December 2017.
Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded.
The remaining 1502 patients were included and their data were reviewed.
The requirement of informed consent was waived by the board
Data collection and definitions
Data from the kidney transplant recipients were collected from the electronic medical records.
Pre-transplant status, including prior history of transplantation, the type and duration of dialysis, history of diabetic nephropathy as a cause of kidney failure, and comorbidities such as hypertension and diabetes, was evaluated.
Results for both recipient and donor ABO blood groups (ABO) and HLA.
Immunosuppressive therapy was determined, including induction therapy with basiliximab or anti-thymocyte globulin, and calcineurin inhibitors for maintenance therapy.
CMV positivity was defined as > 20 copies/ml on polymerase chain reaction or positive result on viral culture, according to the definition of CMV infection.
Transplant outcomes
The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
The secondary outcome was all-cause mortality, based on data obtained from the National.
All patients were followed until graft failure or March 2018.
Data on biopsy-proven acute T-cell-mediated rejection, acute antibody-mediated rejection, and interstitial fibrosis and tubular atrophy were collected.
Protocol biopsies were performed at zero-time, on the 10th day and 1 year after transplantation, and every year thereafter.
Additional kidney biopsies were performed if graft function deteriorated or any suspicious symptoms or signs of rejection were observed.
All pathologic findings were examined by a nephropathologist.
The development of de novo DSA, was defined as any newly developed anti-HLA class I or II antibody
Statistical analysis
All statistical analyses were performed using Stata software. .
Categorical variables were compared using χ2 and Fisher’s exact tests and continuous variables were compared using Student’s t-test.
Risk factors for PCP occurrence were analyzed using univariable and multivariable Cox proportional hazard models.
Propensity score matching was performed to account for the imbalance in baseline characteristics between the PCP-positive and -negative groups.
Scores were created with matching variables including age, gender, donor type, type of pre-transplant dialysis, hypertension, the usage of prophylactic antibiotics, and CMV positivity which had P values under 0.1 in multivariable Cox analysis for the risk of PCP.
Graft survival, overall patient survival, risk of rejection and development of DSA were analyzed using univariable and multivariable Cox proportional hazard models.
A P value < 0.05 was considered to indicate statistical significance
Baseline characteristics and risk factors of PCP
The median duration of follow-up was 6.2 years.
Of the 1502 patients, 68 (4.5%) experienced PCP after kidney transplantation, with an infection rate of 6.8 cases per 1000 person-years.
The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
Discussion
Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured [17, 18].
The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP, and the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
Previous studies have shown that CMV infection increases a risk of PCP [20–22], as supported by the present results.
This may be because CMV might modify the host immune response, leading to immune suppression [23, 24].
T-cells, especially CD4 T cell, are important factors affecting the vulnerability to and resolution of PCP [26], and alteration of the T cell response by CMV might aggravate pulmonary impairment during PCP activation [27].
Findings
Occurrence of PCP was significantly associated with overall graft failure
Outcome univariable multivariable
Interstitial fibrosis and tubular atrophy 1.51 (0.72–3.15) 0.274 1.62 (0.77–3.41) 0.204.
PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
Considering both the significant effect of PCP on mortality and the negative effect on graft outcome over long-term period, prophylaxis against.
The study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
The duration of antibiotic prophylaxis might differ between centers, which could alter the risk of PCP or other transplant outcomes.
This did not hinder the study purpose on the relationship between PCP and transplant outcomes.
Conclusion
Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
Kim et al BMC Nephrology (2019) 20:212 Page 6 of 8 both the risks of mortality and graft failure.
Robust prophylaxis may be needed to prevent PCP and subsequent graft failure.
The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients
I like your detailed summary and analysis.
Background:
Infection is the 2nd most common cause of death in post-kidney transplant recipients after cardiovascular causes.
PCP can occur up to 14% in PKT without prophylaxis with mortality up to 50 % despite aggressive AB treatment.
methods:
This is a retrospective observational study that analyzed 1502 adult patients who underwent kidney transplantation
at Seoul National University Hospital between 2000 and 2017.
Graft & survival outcomes were compared between PCP-positive & negative PKT groups.
PCP was defined as radiological findings by CT plus PCR positivity or direct immunofluorescence of sputum or BAL fluid.
Prophylactic use of AB was defined as TMP/SUL > 4 weeks during the 1st month after kidney transplantation.
results:
4.5 % of patients develop PCP.
Risk factors were lack of initial prophylactic AB prescription & CMV positivity.
The positivity of PCP showed a hazardous ratio of graft failure & mortality in comparison to the negative PCP group but no evidence of subsequent de-novo DSA or pathological evidence of t-cell mediated rejection, Ab-mediated rejection, or IFTA.
conclusion:
The risk of PCP in PKT increased with male gender, CMV positivity & non-use of prophylactic Antibiotic
PCP infection increases risks of mortality & graft failure independent of increased risk of rejections.
The use of prophylactic antibiotics & aggressive treatment of PCP is strongly recommended.
– Level of evidence:
Level III, retrospective observational study
Why would you label this as level III?
Please summarise this article.
Introduction
o The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis (mortality up to 50%)
o The relationship between PCP and mortality was investigated by several studies, but the effect of PCP on graft rejection and overall graft outcomes not well explored
Aim of the study: address the impact of PCP on kidney transplant outcomes, including graft failure and rejection
Methods
o Include total of 1502 kidney transplant patients at Seoul National University Hospital from (2000-2017) (Patients > 18 years and only kidney transplantation)
o The graft and survival outcomes were compared between PCP-negative and PCP-positive groups
o The primary outcome was death-censored graft failure (return to dialysis or kidney retransplantation)
o The secondary outcome was all-cause mortality
Results
o The median duration of follow-up was 6.2 years
o Of the 1502 patients, 68 (4.5%) developed PCP after kidney transplantation (median time was 5.2months and 79.4% of cases developed during the first year after transplantation)
o Positive CMV and the non-use of oral prophylactic antibiotics were risk factors of post-transplant PCP
o Among 68 PCP-positive recipients, 9 (13.2%) patients developed death-censored graft failure (All patients were male with no history of prophylactic antibiotics after transplantation)
o During follow-up, 11 patients (16.2%) and 13 patients (11.0%) died in the PCP-positive and-negative groups, respectively (All-cause mortality was higher in the PCP-positive group than in the PCP-negative group)
o The most common cause of death was acute respiratory distress syndrome related with PCP.
o The PCP-positive group had higher rates of graft failure and mortality than the PCP-negative group (the PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings, such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy)
Discussion
o This study demonstrated that male gender and CMV positivity were risk factors for PCP and the use of oral prophylactic antibiotics prevent the risk of PCP
o The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs
o Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation
Limitations of the study:
1. A retrospective study
2. Duration of prophylactic antibiotics was 1month, which was shorter than the guideline recommendation (i.e., 3–6months), which might increase overall risk of PCP in study subjects
3. The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP
Conclusions
o Risk of PCP include male gender, positivity for CMV, and non-use of oral prophylactic antibiotics
o PCP is a risk factor of both mortality and long-term graft failure, , irrespective of rejection
o Appropriate prophylaxis may be needed to prevent PCP and subsequent graft failure
What is the level of evidence provided by this article?
A retrospective observational study (level III)
I like your listing of limitations of this study.
Thank you prof
Impact of Pneumocystis jirovecii pneumonia on Kidney transplant outcome:
Background
Death-related graft failure had been dramatically improved as a result of improving immunosuppressant protocols, more studies and observation are needed to reduce death-unrelated graft failure, to improve the total causes of mortality (opportunistic infection).
Infection is an important second factor of death in functioning graft recipients, following cardiovascular disease.
Pneumocystis jirovercii is an opportunistic infection in an immunocompromised recipient with an incidence of 0.6 to 14% among kidney transplant recipients and mortality of up to 50% although aggressive antibiotic therapy.
This Article assesses the effect of PCP on kidney transplant outcomes, including graft failure and rejection.
Discussion
Limitation of the study
Conclusion
Level of evidence
Level ((III)), retrospective study
I like your listing of limitations of this study.
Typing whole sentence in bold or capitals equals to shouting !
thank u Prof
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Introduction
· Infection is the second most common cause of death after CVD in patients with functioning grafts.
· The incidence of P. jirovecii pneumonia (PCP) is 0.6 to 14% among kidney transplant recipients without prophylaxis.
· Mortality related to PCP is up to 50% despite aggressive antibiotic therapy.
· The effect of PCP on graft rejection and overall graft outcomes has been less-well studied.
Methods
· This retrospective observational study.
· Included 1502 patients who had kidney transplantation without pancreatic transplantation and above 18 years of age at Seoul National University Hospital from January 2000 to December 2017.
· PCP was defined as the presence of findings suspicious of PCP on chest CT plus PCP positivity on PCR or direct IF stain of sputum or BAL fluid.
· CMV positivity was defined as >20 copies/ml on PCR or positive viral culture.
· The primary outcome was death-censored graft failure defined as a return to dialysis or kidney retransplantation.
· The secondary outcome was all-cause mortality.
Results
· 4.5% experienced PCP after kidney transplantation
· CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
· There was a significant relationship between PCP and graft failure, with HRs of 3.34 and 3.33 respectively.
· PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients (adjusted HR, 3.06 P=0.027).
· All the patients who developed graft failure were male and had no history of prophylactic antibiotics usage after transplantation.
· All-cause mortality was higher in the PCP-positive group than in the PCP-negative group
· The PCP-positive group had a significant higher risk of mortality adjusted HR, 10.99.
· Nine of Eleven patients died within 3 months after the occurrence of PCP. The most common cause of death was acute respiratory distress syndrome related with PCP.
Discussion
· The clinical implications, especially in relation to graft outcomes, have not been fully evaluated.
· The results of the present study demonstrated that male gender and CMV positivity were risk factors associated with PCP.
· The use of oral prophylactic antibiotics seemed to prevent the risk of PCP
· PCP increased the risk of long-term graft failure; however, this was not related to rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
· As, PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
· In this study pre-transplant dialysis was identified as a protective factor of PCP, resolution of uremia would decrease the risk of PCP. Further studies are needed in the aspect.
· PCP itself did not affect the risk of acute rejection and de novo DSA production. The occurrence of PCP was significantly associated with overall graft failure probably due to non-immunological factors such as the production of proinflammatory cytokines.
· Mortality risk was elevated in patients with PCP in the first 3 months after diagnosis of PCP infection. The cause of death was either PCP itself or the other infection superimposed on PCP.
Conclusion
· PCP significantly increases both the risks of mortality and graft failure. Accordingly, vigorous prophylaxis may be needed.
2. The level of evidence is 3
Why would you label this as 3?
What are strengths and limitations of this study.
1-Please summarise this article.
Introduction;
-Infection is an important factor in relation to the risk of death in kidney transplant recipients, and the second most common cause of death after cardiovascular disease in patients with functioning grafts.
-Pneumocystis jirovecii is an ascomycetous fungus that causes opportunistic infections, and its life cycle remains unknown because it cannot be consistently cultured.
-The incidence of P. jirovecii pneumonia (PCP) varies from 0.6 to 14% among kidney transplant recipients without prophylaxis, with a mortality of up to 50% despite aggressive antibiotic therapy.
Methodology;
-This study included total 1827 patients who had kidney transplantation at Seoul National University Hospital from January 2000 to December 2017.
-After excluded (325 patients; the remaining 1502 patients were finally included and their data were reviewed.
–Exclusion criteria; Patients who were under 18 years old (n = 260) or who received simultaneous kidney–pancreas or kidney–liver transplants (n = 65) were excluded.
-After a propensity score matching was performed,the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
Results;
–The median time to the development of PCP was 5.2 months, and 79.4% of cases developed during the first year after transplantation.
-There were significant differences between PCP-positive and -negative patients with respect to gender, type of pre-transplant dialysis, ABO-incompatibility, desensitization therapy, induction regimen, hypertension and CMV positivity.
-After adjustment for multiple covariates, CMV positivity and the non-use of oral prophylactic antibiotics were associated with an increased risk of PCP.
-Although the acute T cell-mediated and antibody-mediated rejection episodes or other immunological findings such as interstitial fibrosis and tubular atrophy and de novo DSA were additionally adjusted.
-The PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients .
-Mortality risk was elevated in patients with PCP. Nine out of eleven (81.8%) patients died within 3 months after diagnosis of PCP infection.
-The causes of death in these patients were either PCP itself or the other infection superimposed on PCP.
-During the follow-up period, 11 patients (16.2%) died in the PCP-positive and 13 patients (11.0%) died in PCP-negative groups.
-The 28 PCP-positive patients had concurrent other infectious diseases, and 8 patients died (28.6%).
-The PCP-positive group had a higher risk of mortality than the PCP-negative group.
-The most common cause of death was acute respiratory distress syndrome related with PCP.
-CMV infection increases a risk of PCP , as supported by the present results.
-This may be because CMV might modify the host immune response, leading to immune suppression.
-CMV infection affects the T cell compartment and accelerates aging of T cells; especially CD4 T cells which are important factors affecting the vulnerability to and resolution of PCP.
-Alteration of the T cell response by CMV might aggravate pulmonary impairment during PCP activation.
Conclusions;
-Although PCP is relatively common after kidney transplantation, its clinical implications, especially in relation to graft outcomes ,have not been fully evaluated.
-The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
-Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
-According to the KDIGO, it is recommended that all recipients receive prophylaxis against PCP for 3–6 months after transplantation.
-Risk of PCP is aggravated in the kidney transplant cases with male gender, positivity for CMV, and non-use of oral prophylactic antibiotics.
Limitation;
-Although this study achieved its primary purpose by demonstrating the relationship between PCP and transplant outcomes.
–It was a retrospective study, making it difficult to demonstrate cause and effect definitively.
-The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (3–6 months), which might increase overall risk of PCP in study subjects.
-However, definitive guidelines on the duration and dosage of PCP prophylaxis are not available and more research is needed to determine the appropriate approach.
-The duration of antibiotic prophylaxis (more than 4 weeks) might differ between centers, which could also alter the risk of PCP or other transplant outcomes.
-The present observational study design could not determine the mechanisms underlying the risk and subsequent effect of PCP.
2-What is the level of evidence provided by this article?
Retrospective observation study
This retrospective observational study;
Level of evidence III
I like your listing of limitations of this study.
Typing whole sentence in bold or capitals equals to shouting !
Impact Of Pneumocystis Jirovecii Pneumonia on Kidney Transplant Outcome
1. Please summarise this article.
Introduction:
Infection is a significant risk factor for mortality in kidney recipients and it is following cardiovascular disease (CVD) in order as the second most common cause of death with a functioning graft.
Pneumocystis jirovecii (PJP), previously known as pneumocystis carinii (PCP) is one of the opportunistic infections that causes serious pneumonia in immune compromised patients.
P. jirovecii pneumonia (PJP) occurs in 0.6 to 14% of kidney transplant patients without prophylaxis, with a 50% mortality rate despite rigorous antibiotic treatment. PCP has been linked to mortality, but its impact on graft rejection and outcomes has been less studied.
The impact of PJP on allograft rejection and outcomes is unknown.
Aim of the study:
Aim to Evaluate of PCP infection impact on kidney graft outcome including failure and rejection.
Method of study :
The primary outcome:
Death-Censored Graft Failure
The secondary outcome: all-cause mortality.
Statistical analysis:
Results:
1) CMV +ve patients
2) Absence of prophylaxis
3) male gender.
Discussion:
Limitations:
Conclusion:
Prophylaxis is needed to prevent PJP and graft failure in kidney transplant recipients.
Adequate duration of prophylactic antibiotic reduces the risk of PJP infection in solid organ transplantation and its consequent effect on graft failure/mortality.
More RCTs needed to give us information about PJP prophylaxis in kidney recipient patients.
2. What is the level of evidence provided by this article?
Level of evidence III, Retrospective observation study
I like you listing of limitations of this study.
Typing whole sentence in bold or capitals equals to shouting !
– Infection is considered the second most common cause of death in renal replant recipient s after cardiovascular disease
– Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that cause severe lung injury, and is associated with increased morbidity and mortality in renal transplantation
– The Incidence varies between 0.6-14% , and once occur around half of the cases die despite treatment
– This is a retrospective study evaluating 1502 renal transplant recipients at single center between 2000 and 2017 and asses the following :
Results:
Conclusions:
What is the level of evidence provided by this article?
Why would you label this as III? I like your summary
Because it is a retrospective study
Summary
Introduction
Infections are the second most common cause of death in kidney transplant recipients with a functioning graft.
PCP is an opportunistic infection that causes a pulmonary infection in immunocompromised persons.
Incidence rate of PCP varies between 0.6-14% in kidney transplant recipients without prophylaxis, and its mortality can go up to 50%.
Aim of this study:
To determine the impact of PCP on kidney transplants outcomes including graft failure and rejection.
Methodology:
This was a retrospective observational study in Seoul. Carried out between January 2017 and December 2017.
They included 1502 participants.
Exclusion criteria:
They were followed till March 2018 or they developed graft failure whichever occurred earlier.
PCP was diagnosed by the presence of finding suspicious for PCP by a radiologist on CT chest plus PCR positivity or direct immunofluorescence stain of sputum or BAL.
CMV positivity was diagnosed as >20 copies/ml.
Primary outcome: death censored graft failure
Secondary outcome: All cause mortality.
Results:
68 participants (4.5%) developed PCP. Median time to infection was 5.2 months.
79.4% of the infections occurred in the first year post transplant.
Median time of followup was 6.2 years.
Of the 68, 9 had death censored graft failure and died within 3 months after occurrence of the PCP, cause of the death was ARDS secondary to PCP.
The nine patients were all males and were not on antibiotic prophylaxis.
Of the 68, 28 had concurrent other infections and 8 of them died.
11 (16.2%) and 13(11%) patients in the PCP positive and negative group died.
All cause mortality was higher in the PCP positive group.
Eight out of the nine patients with death censored graft failure had acute kidney injury.
Discussion:
Life cycle of PCP is unknown because it can’t be consistently cultured.
Male gender and CMV positivity were risk factors associated with PCP.
Oral prophylactic antibiotics seem to prevent the risk.
PCP increased the risk of long term graft failure.
This study supports previous studies results that CMV infection increases risk of PCP infection.
Pre-transplant dialysis was associated as protective factor, could be due to clearing the uraemia state that is associated with altered immunological response.
PCP infection didn’t increase the risk of rejection suggesting non-immunological factors may be associated.
Mortality was high in the PCP positive group caused of death was either the PCP itself or there infections superimposed on the PCP.
Thus prophylaxis is strongly recommended.
Limitations:
Strengths:
It was able to demonstrate relationship between PCP and outcome.
Conclusion:
Risk for PCP is high in kidney transplant recipients who were male, had CMV positivity and were not on antibiotic prophylaxis. PCP increases risk of mortality and graft failure. Hence prophylaxis required to prevent PCP and subsequent graft failure.
Level of evidence: 3
Why would you label this as 3?
I like your listing of strengths and limitations of this study.
Thank you prof.
This was a retrospective observational study giving it a level 3 in the pyramid
Please summarise this article.This is a retrospective observational study from a single center in the south Korean population with a follow-up period of 17 years, data were collected from electronic medical records in the period between 2000-2017, and the aim of this study was to determine the impact of PCP infection on the overall graft and patient survival, and the immunological impact on rejection
Study design and methods
A retrospective observational study from a national university single center included 1502 kidney transplant recipients from 2000-2017 after the exclusion of those under the age of 18 years or those with dual transplantation ( kidney & liver or kidney &pancreas ), the patient’s clinical characteristics and demographic were taken from electronic medical records in addition to the ABO compatibility, HLA typing, and Mismatches, induction type basiliximab Vs ATG and maintenance immunosuppression types ( the use of triple maintenance immunosuppression including steroid, MMF, and CNI ), re transplantation, They use the definition of PCP as the presence of findings suspicious of PCP detected by a radiologist on chest computed tomography combined with PCP positivity on polymerase chain reaction or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid. They use cotrimoxazole as prophylaxis from the first 4 weeks following kidney transplantation, they don’t have to use pentamidine or atovaquone as alternative prophylaxis. they defined CMV positivity as > 20 copies/ml on polymerase chain reaction or a positive result on viral culture.
They screen for graft rejection by protocol biopsies starting from day 0, pre-transplantation then annual protocol biopsy or whenever indicated, also DSA monitoring for denovo DSA for both class1, 11
The primary outcome of this study was death-censored graft failure (return to dialysis or kidney re-transplantation).
The secondary outcome includes all-cause mortality outcome and impact on graft survival including rejection and graft failure.
Results
Table 1 shows the total patients’ clinical characteristics and demographics, median FU of 6.2 years, from a total of 1502 patients only 68 ( 4.5%) got PCP with an infection rate of 6.8 cases/1000 persons /year with medium-time for PCP infection around 5.2 months .majority of PCP infection occur after 1 year of transplantation in 79% of cases, more in male recipients, also PCP prevalence was more in ABO Incompatible and those underwent desensitization, induction type of IS and CMV co-infection, After modification for many covariates, only CMV positivity and the non-use of oral prophylactic antibiotics was associated with an increased risk of PCP.
PCP infection and graft outcome
Between 68 PCP-positive recipients, 9 (13.2%) patients established death-censored graft failure. the PCP-positive recipients had a higher risk of death censored graft failure than the PCP-negative recipients
(Adjusted HR, 3.06 [1.14–8.26]); P = 0.027)
Higher rate of graft failure in PCP-positive recipients and it’s due to non-immunological factors such as concurrent acute kidney injury.
All-cause mortality was higher in the PCP-positive group than in the PCP-negative group. The most common cause of death was acute respiratory distress syndrome related to PCP within the first 3 months of infection. No difference in the rate of acute TCM, AMR, or denovo DSA between the two groups.
Discussion
The results of this study confirmed that male gender and =infection with CMV plus non-use of antibiotics prophylaxis are major risks for PJP after kidney transplantation infection can impact the graft and patient survival and was not through the rejection episodes or IFTA or denovo DSA, and the aggressive treatment and antibiotics prophylaxis is mandatory after kidney transplantation.
Previous studies supported the finding of this study in regards to CMV co-infection and the risk of PCP as CMV can affect the T cell immune response like CD4, this alteration in T cell response by CMV might aggravate
pulmonary impairment during PCP activation.
Conclusion:
this observational study confirms that male gender and CMV – co-infection with non-use of prophylaxis AB as major risks factors for PCP after transplantation also PCP infection can impact both graft and patient survival mainly through non-immunological effects, we need more future studies to address the best timing and duration of AB prophylaxis after transplantation
Limitations of the study
1. Retrospective design
2. The definition of AB prophylaxis within 4 weeks? Which is shorter than the duration recommended by the KDIGO guideline ( 3-6 months ).
3. The current observational study design could not determine the mechanisms underlying the risk and sub[1]sequent effect of PCP.
2. What is the level of evidence provided by this article?
level 3, retrospective observational study
The Aim of the Study ;
To evaluate the impact of PCP on kidney transplant outcomes, including graft failure and
rejection.
The Type of the Study ;
This retrospective observational study.
Ethical Approval ;
Was approved by the institutional review board of Seoul National University Hospital and complied with the Declaration of Helsinki.
The Population ;
1502 kidney transplant recepients.
The Exclusion Criteria ;
1-Patients who were under 18 years old .
2- Patients who received simultaneous kidney–pancreas or kidney–liver transplants .
The Method;
This retrospective observational study analyzed 1502 adult patients who underwent kidney transplantation at Seoul National University Hospital between 2000 and 2017. After a propensity score matching was performed, the graft and survival outcomes were compared between PCP-negative and PCP-positive groups.
The Result of the Study ;
1- The multivariable Cox analysis showed that positivity for cytomegalovirus and lack of initial oral antibiotic prophylaxis were risk factors of post-transplant PCP.
2-The PCP-positive group had higher hazard ratios of graft failure and mortality than the PCP-negative group.
3-The PCP event was not related with subsequent development of de novo donor-specific antibodies or pathologic findings ,such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
The Limitations of the Study ;
1-It was a retrospective study, making it difficult to demonstrate cause and effect definitively.
2-The current definition of prophylactic antibiotics was 1 month, which was shorter than the guideline recommendation (i.e., 3–6 months), which might increase overall risk of PCP in study subjects.
Conclusion;
1-The results of this study demonstrated that male gender and CMV positivity were risk factors associated with PCP.
2-The result of this study demonstrated that ,the use of oral prophylactic antibiotics seemed to prevent the risk of PCP.
2-The occurrence of PCP increased the risk of long-term graft failure; however, this relationship was not dependent of rejection, interstitial fibrosis and tubular atrophy, or de novo DSAs.
3-The results of study demonstrated that , PCP did not increase the risk of any rejection after infection, suggesting that non-immunological factors may be the cause underlying the observations.
4-Because PCP was associated with both graft failure and overall mortality, intensive treatment and prophylaxis is recommended after transplantation.
5-The present results will be the basis of the future clinical trials on the use of prophylaxis in kidney transplant recipients.
What is the level of evidence provided by this article?
Level III
Why would you label this as level III?
Please use bold or underline for headings or sub-headings to make it easier to read.
Thanks Professor
I will do
This is retrospective observational study
1- Summary:
Objectives: To evaluate the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Material and methods:
Results:
Conclusion:
PCP is a risk factor of long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment is needed to avoid adverse transplant outcomes of PCP.
II- level of evidence: IIIb
Why would you label this as IIIb?
it is a retrospective study
I am sorry it was a writing mistake. the level according to Oxford level of evidence is IIb
Please summarise this article.
Background
Method
Results
Discussion
Limitations:
Conclusion:
============================================
What is the level of evidence provided by this article?
Level of Evidence III
I like your detailed summary and analysis.
1.Please summarize this article.
Introduction
The study
The primary outcome:
The secondary outcome:
Results
Baseline characteristics & risk factor of PCP:
PCP & transplant outcomes:
Discussion
Limitations
=========================
2. What is the level of evidence provided by this article?
I like your detailed summary and analysis. What is the difference between retrospective cohort or a case-control study?
Thank you, dear Prof Ajay
A case-control study attempts to identify potential exposure factors following a known disease incidence, whereas a retrospective cohort study compares the risk of getting a disease to some already known exposure factors.
Please use bold or underline for headings or sub-headings to make it easier to read.
I.Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
====================================================================
Please summarise this article.
Background
====================================================================
Methods
Transplant outcomes
Statistical analysis
====================================================================
Results
Baseline characteristics and risk factor of PCP
PCP and transplant outcomes
====================================================================
Discussion
====================================================================
Conclusion
====================================================================
What is the level of evidence provided by this article
I like your detailed summary and analysis. What is the difference between retrospective cohort or a case-control study?
Many thanks Prof.Sharma
=============================================================
Please summarise this articlePneumocystis jirovecii (PJ) is a notable cause of morbidity and mortality in solid organ transplant recipients. This study assessed the effect of PJ infection on kidney transplant outcomes.
Methods:
Results:The PCP positive and negative groups were matched using propensity score matching.
Incidence of PCP
The following risk factors were associated with an increased risk of PCP.
PCP-positive recipients had a higher risk compared to PCP negative in terms of
PCP had no effect on risk of
Limitations
Conclusion:Adequate duration of prophylactic antibiotic reduces the risk of PC infection in solid organ transplantation and its consequent effect on graft failure/mortality What is the level of evidence provided by this article?Case-Control retrospective study:Level 3b
Why do you label this as a case-control study?
Retrospective cohorts comparing PCP negative and positive groups on kidney transplant outcomes
Introduction:
Aim of the study:
Methods:
Result & discussion:
Level of evidence is 3
what is the difference between retrospective cohort or a case-control study?
Retrospective study when the researcher start the study at the time follow-up has already completed.
Case control study when the researcher select cases & control depending on presence or absence of outcome & loopback in time for disproportionate exposure.
Please summarize this article
Introduction
Methodology
Results
Conclusion
What is the level of evidence provided by this article?
what is the difference between retrospective cohort or a case-control study?
Thank you, prof
Summary : Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome
Introduction
This article is concerned with the effect of pneumocystis jirovecii pneumonia on long term graft outcome and mortality.
About the offending agent
Pneumocystis jirovecii is a fungus that causes opportunistic infections. The purpose of this article also goes toward identifying whether the long term effect of OCO on allograft is due only to infection, or combined with other reasons such as chronic inflammation. This is an area that warrants more research.
Outline of the study
This study demonstrates that PCP risk was increased in cases of positive CMV and with male patients. In contrast, the risk of PCP greatly reduced with oral use of prophylactic antibiotics. PCP can lead to long term graft damage and even failure. This is not found to be associated with rejection, interstitial fibrosis, tubular atrophy, or de novo DSAs.
Due to the intensity of the complications caused by PCP, aggressive post transplant prophylaxis and treatment is recommended.
Discussion
PCP has been linked to male gender and CMV infection. CMV increases PCP risk in both male and female patients, and this could be attributed to CMV modifying the host immune response, resulting in immune suppression. IT affects the T cells and speedens aging in these cells, weakening immune response of the host and making it difficult to prevent or resolve PCP in the patient. Lung impairment is a significant clinical feature.
Protective factors against PCP include prophylactic antibiotics and pre transplant dialysis. Since uremia is linked to altered immune response, dialysis could help with resolution of uremia to an acceptable level, thus decreasing the risk of post transplant PCP. It is worth it to note that long term dialysis prior to transplant can have an opposite effect on the immune system and thus PCP incidence. Frequency and dose of dialysis may play a role in the outcome.
In addition, incidence of PCP did not increase the risk of acute rejection or de novo DSA production.
Conclusion
KDIGO guidelines recommend that all kidney transplant recipients receive prophylaxis against PCP for a period of 3-6 months post transplant. Limitations of this study include retrospective nature of the study making is difficult to clearly demonstrate cause and effect. In addition, this study used a very short period of prophylactic antibiotics (1 month) in comparison with guideline recommendations, thus leaving the possibility of increased risk of PCP.
Robust prophylaxis may be necessary to prevent PCP and long term graft damage or failure in these patients.
Level of evidence
This is a retrospective observational study looking for risk factor with subject of interest, and thus level of evidence is 3.
Is it a retrospective cohort or a case-control study?
Introduction
Pneumocystosis is an opportunistic disease that causes severe interstitial pneumonia with high mortality in patients who have undergone solid organ transplantation.
Materials and methods
A single-center retrospective observational study conducted at Seoul University Hospital between 2000 and 2017 compared groups with and without pneumocystosis, setting the level of evidence 3.
Protocol biopsies were performed on D+0, D+10, and D+365 of the Transplant. Additional biopsies were performed if necessary.
Objectives
Primary – Graft failure and loss
Secondary – Mortality related to all causes
Results
The medical follow-up time was six years and two months. 1502 patients were followed with 68 patients presenting with infection (4.5% and 6.8 cases per thousand patients). After five months is the average time to present infections with 79.4% of cases in the first year.
Risk factors were male gender, ABO incompatibility, desensitization, and CMV positivity.
Pneumocystosis has HR 3.34 for graft failure and 3.06 for graft loss.
All-cause mortality was higher in the Pneumocystosis positive group with HR 10.99 being the main cause of mortality respiratory failure triggered by Pneumocystosis itself.
Discussion
The presence of CMV infection and the use of anti-lymphocyte drugs increase the risk of pneumocystosis. Its occurrence does not affect the risk of acute rejection or de novo DSA production.
Limitations
Retrospective study, making cause and effect difficult. In that center, prophylaxis was only for one month, against most guidelines that suggest 3 to 6 months of prophylaxis.
Conclusion
Pneumocystosis has a high risk of loss of graft function and there is a need for prospective studies to define the adequate duration of post-transplantation prophylaxis.
Is it a retrospective cohort or a case-control study?
Retrospective and observational
Introduction:
Pneumocystis jirovecii produces severe lung infections in immunocompromised patients. P. jirovecii pneumonia (PCP) occurs in 0.6 to 14% of kidney transplant patients without prophylaxis, with a 50% mortality rate despite rigorous antibiotic treatment. PCP has been linked to mortality, but its impact on graft rejection and outcomes has been less studied.
Method:
This was a retrospective study that looked at 1502 adult patients who had kidney transplants at Seoul National University Hospital between the years 2000 and 2017. Following the completion of a propensity score matching procedure, a comparison of the graft and survival results between PCP-negative and PCP-positive groups was carried out.
Results:
68 transplant recipients (4.5%) developed PCP. Cytomegalovirus positivity and absence of oral antibiotic prophylaxis were risk variables for post-transplant PCP in the multivariable Cox analysis.
The PCP-positive group exhibited greater hazard ratios of graft failure (3.1 (1.14–8.26); P = 0.027) and death (11.0 (3.68–32.80); P < 0.001) than the PCP-negative group. However, PCP did not cause de novo donor-specific antibodies or pathologic features such as T-cell or antibody-mediated rejection, interstitial fibrosis, or tubular atrophy.
Conclusion:
A positive test for CMV, the absence of oral prophylactic antibiotics, and a male gender all contribute to an increased risk of post-transplantation pneumonia (PCP).
PCP is a risk factor for long-term graft failure and mortality, irrespective of rejection. Accordingly, appropriate prophylaxis and treatment are needed to avoid the adverse transplant outcomes of PCP.
it is possible that rigorous prophylaxis will be required to avoid PCP and the eventual failure of the transplant. The current findings will serve as the foundation for future clinical studies concerning the administration of prophylaxis to patients with kidney transplants.
Level of evidence III, Retrospective observation study
Is it a retrospective cohort or a case-control study?
retrospective cohort
1-Background
Infection is the second most common cause of death after cardiovascular disease in patients with functioning grafts.
Pneumocystis jirovecii is an opportunistic pathogen which can lead to severe pulmonary infection in immunocompromised cases . P. jirovecii pneumonia (PCP) incidence is 0.6 to 14% in renal transplant recipients without prophylaxis, mortality can reach up to 50% even with intensive antibiotic therapy.
Unlike the effect of CMV and BKV on graft rejection ,the effect of PCP on graft rejection is less evaluated .
Aim
Access the impact of PCP on kidney transplant outcomes, including graft failure and rejection.
Methods
This is a retrospective observational study involving 1502 renal transplant recipients at Seoul National University Hospital within 17 year .
Medical details were obtained from records and PCP was diagnosed through CT findings and PCR or direct immunofluorescence stain of sputum or bronchoalveolar lavage fluid.
Cases were considered CMV positive if > 20 copies/ml on PCR or positive result on viral culture.
The primary outcome was considered death-censored graft failure ,through dialysis or renal retransplantation and the secondary outcome was all-cause mortality.
Both outcomes were compared between PCP-negative and PCP-positive groups
Results
4.5% of the cases experienced PCP post transplantation. The risk factors of post-transplant PCP were CMV positivity and lack of oral antibiotic prophylaxis . Graft failure and mortality were higher in the PCP-positive group than the PCP-negative group. Meanwhile PCP was not associated with DSA occurrence or pathologic findings,such as T-cell or antibody mediated rejection and interstitial fibrosis and tubular atrophy.
Discussion
Pneumocystis jirovecii is an ascomycetous fungus that leads to opportunistic infections,it’s mechanism of graft affection is not investigated nor it’s outcomes evaluated.
Risk factors for PCP included male gender, CMV positivity while oral prophylactic antibiotic and pretransplant dialysis by decreasing uremia seemed to lower the risk.
CMV infection impairs CD4 T cell response thereby rendering the patient vulnerable to pulmonary infection by PCP .
PCP increased graft failure risk apart from rejection ,tubular atrophy and DSA .
It was suggested that PCP affect the graft in a non immunological way by stimulating the production of proinflammatory cytokines.
Therefore treatment and prophylaxis are mandatory.
KDIGO recommended that prophylaxis against PCP must be given to renal transplant recipients for 3–6 months after transplantation.
Limitations were being a retrospective study, antibiotic prophylaxis was 1 month rendering cases more liable to PCP infection also prophylaxis duration varied between centers ,another aspect is that this study wasnot able to detect the mechanisms which increases the risk and subsequent effect of PCP.
Conclusion
PCP is a risk factor for graft failure on the long term and mortality, apart from rejection.
Prophylaxis and treatment is crucial to avoid PCP and it’s complications.
2-Level of evidence is 3 as it is a retrospective study
Is it a retrospective cohort or a case-control study?
Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome:
1- Infection account 20 % (second cause of death) of mortality in SOT after cardiovascular complications which account 40% and remains the first cause of death with functioning graft.
2- Pneumocystis jirovecii pneumonie PCP is an an ascomycetous fungus opportunistic organism has 0.6-1.4% incidence of infection in renal transplant recipient without use of prophylaxis, and its mortality reaches 50% even with aggressive treatment.
3- Long term graft failure in association with PCP is not known it is due to infection or due to associated chronic inflammatory process or other factors.
4- Male gender and CMV are important risk factors associated with PCP.
5- Long term prophylaxis of PCP is associated with decrease incidence.
6- Aggressive treatment of PCP post transplant is important as it may associated with rejection and risk of other infections like CMV.
7- CMV infection is important risk factor for PCP as CMV alter T cell immune response especially CD4 which is important in aggravation or suppression of PCP.
8- Pre-transplant dialysis or uremia alters the immune response and increase risk of PCP post transplant.
9- The occurrence of PCP itself did not affect the risk of following development of acute rejection and de novo DSA production.
10- Occurrence of PCP was significantly not associated with overall graft failure.
11- Infections may also induce allograft injury (non-immune mechanism) by stimulating the production of proinflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8, these proinflammatory cytokines are known to be upregulated in patients with PCP.
12- Mortality with PCP is high either due to PCP itself or other associated infections.
13- Prophylactic treatment of PCP is highly recommended for 6 months post transplant to avoid high risk of mortality.
level of evidence 3
Is it a cross-sectional study or a longitudinal study?
Is it a retrospective cohort, diagnostic risk assessment or a case-control study?
it is retrospective cohort