Please counsel this patient discussing the pros and cons of transplantation.
Will you elaborate more on HIVAN?
What are the chances of recurrence of HIVAN post-transplantation?
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Mohammed Sobair
Please counsel this patient discussing the pros and cons of transplantation.
Pros:
Survival rate is better than hemodialysis.
1 and 3 years patient. And graft survival is similar to non HIv.
Cons:
There risk of recurrence of diseases.
Risk of opportunistic infection.
Risk of acute rejection.
Theoretical risk of more posttransplant malignancy.
HIV-associated nephropathy (HIVAN) is a renal parenchymal disease that occurs
exclusively in people living with HIV. It is a serious kidney condition that may possibly lead to end-stage kidney disease, particularly in the HIV-1 seropositive patient.
What are the chances of recurrence of HIVAN post-transplantation?
Risk of recurrence is remote and further studies on going to elaborate more evidence.
· Please counsel this patient discussing the pros and cons of transplantation. Always transplant has been a better option then dialysis in ESRD patients. To decrease the burden of dialysis and quality of life transplantation is a better option. Proceeding for transplantation of HIV patient should be council for future recurrence of renal disease. · Will you elaborate more on HIVAN? HIVAN is the fate of HIV patients it not treated, its late consequence of the disease. Usually these patient present with constitutional symptoms of recurrent infection, proteinuria, worsening renal function, and progressive renal failure. Literature shows some association of genetic propenicity with HIVAN an apoliprotien (APOL1). The most common presentation is GN with FSGS. · What are the chances of recurrence of HIVAN post-transplantation? Its significant concern of recurrence of disease. To prevent the recurrence of disease, however, higher the viral load, there is higher risk of recurrence of disease. The HIV copies should be less than 50 to proceed for transplantation, CD4+T cell should be more then 200, Treatment with HAART, Pre-transplantation prophylactic, for PCP, CMV, Vaccination for HBV, HAV, HZV, HPV, DPT, and MMR Post-transplant annual vaccination,
Human immunodeficiency virus (HIV) infection has been associated with both acute kidney injury (AKI) and chronic kidney disease (CKD) )HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS [1-3] although HIVAN may also occur in patients with less advanced HIV infection or following acute seroconversion [4,5]. Histologically, HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation [6].
Issues related to HIVAN will be discussed in this topic. An overview of kidney disease in people with HIV and discussions of electrolyte abnormalities, dialysis, and transplantation in people with HIV are provided elsewhere
Please counsel this patient discussing the pros and cons of transplantation. · Kidney transplantation is the best option for an ESRD patients including HIV-related recipients. · HIV positive patients was not a common entity but this has changed in recent years with the use of the new HAART medications · HIV + recipients should receive proper counseling about the pros and cons of renal transplantation compared to staying on dialysis. Pros: · Provides hope for HIV+ recipients who utilizes the currently available cART if they fulfill certain criteria · Better patient survival and quality of life than remaining on dialysis. · Utilizing HIV+ donors to HIV + recipients reduces the transplant waiting time · Opportunistic infections that occur in the post-transplant period is not higher in HIV+ ve compared to HIV –ve recipients. Cons: · Increased rejection rates (2-3 times) including steroid-resistant rejection and delayed graft function compared to the general population. · More drug interactions between cART and immunosuppressive agents · Increased risk of malignancy associated with human papilloma virus, no increase in other malignancies · Increased incidence of bacterial infections · HIV AN recurrence after transplantation
Will you elaborate more on HIVAN? · HIV-associated nephropathy (HIVAN) is the first kidney disease diagnosed in HIV-infected patients · Risk factors: o Race: 50 times more in African-Americans than in whites, with increased risk with presence of 2 APOL1 risk alleles o proteinuria >3g per day and higher serum creatinine from baseline o High viral load (>400 copies/ml) and CD4 count <200 · Clinical picture: o Proteinuria (usually heavy up to nephrotic). However, edema and hypertension arenot typically present. o Rapid decline in renal functions to ESRD · Diagnosis: o Urine examination show a bland urinary sediments o US shows enlarged swelling echogenic kidneys o Biopsy is required to differentiate from other cause and show collapsing FSGS, interstitial nephritis, visceral epithelial cell proliferation, endothelial tubuloreticular inclusions, and tubular microcystic dilatation. The Tubulo-interstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease. · Management: o Initiation of cART (regardless of CD4 count), o Control of proteinuria with ACE inhibitors or ARBs o Steroids to reduce tubule-interstitial inflammation o If ESRD developed, renal replacement therapy in form of dialysis and transplant( offered to patient who fulfills certain criteria) is available.
What are the chances of recurrence of HIVAN post-transplantation? · Chances increase if the donor is HIV-positive. However, there is no correlation between the recurrence of HIVAN and viral loads. · The chances for recurrence depends on the adequacy of the treatment of HIV with cART. So, if managed well keeping in mind the interaction with transplant immunosuppression. The chances will be low. · The location of the viral reservoir in the transplanted kidney is important as graft function deteriorate if the virus is identified in the podocytes and not in the tubular cell of the transplanted kidney.
References: 1. Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11. 2. Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. 3. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. 4. British Transplantation Society. Kidney and Pancreas Transplantation in patients with HIV, 2nd ed.; British Transplantation Society: Macclesfield, UK, 2017
Please counsel this patient discussing the pros and cons of transplantation.
HIV positive patients had been successfully transplanted for the last 15 years and the donor pool had successfully been expanded to also include HIV positive donors. HIV positive patients should be selected for transplantation according to standard selection criteria, similar to HIV negative transplant recipients. Additional recommendations, specific to HIV, include: -patient should be virally suppressed (undetectable viral load) and be on a stable ART regimen for at least 3 months before the date of the transplant. -patients must have a CD4 count above 200 cells/mm3, but patients with lower CD4 counts. Pros: – improved quality of life and better long-term prognosis and survival. -Opportunistic infections encountered post-transplant in HIV-positive patients are not significantly higher than HIV-negative recipients . Cons – rejection rates and DGF are higher than in the general population . -Increased incidence of bacterial infections Only patients with fully treated tuberculosis should be considered for transplantation. -drug-drug interactions between cART and immunosuppressive agents . superior outcomes had been reported with integrase strand transfer inhibitor-based antiretroviral regimens, as there is no interaction with calcineurin inhibitors but if this no available the PIs have been used to decrease the amount of CNI that the HIV positive recipients require, hence saving drug costs . – Patients with opportunistic infections and neoplasms without effective medical therapy are generally excluded (PML, chronic intestinal cryptosporidiosis). –ATG has been shown to be associated with decreased patient and graft survival and it is better to use basileximab -In the case of using HIV positive deceased donors, particular attention should be given to the risk of donor derived infections like latent tuberculosis and strongyloidiasis in endemic areas. Screening for sexually transmitted diseases such as syphilis, West Nile Virus and Chagas parasitic disease are important. –De novo HHV8- mediated Kaposi’s sarcoma (KS) had been reported in some HIV infected transplant recipients, but switching immunosuppressive regimens to include TOR inhibitors generally controlled this. – Chronic immune activation and inflammation is known to contribute to the risk of cardiovascular diseases in HIV positive patients.
Will you elaborate more on HIVAN?
Pathologically HIVAN is defined by: -a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy. -Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features. -In ART-treated patients, a non-collapsing form of FSGS called FSGS (NOS) is more commonly encountered at biopsy. -Numerous forms of immune complex-mediated glomerular disease have been reported in HIV-positive individuals. -These immune complex-mediated glomerular diseases can include multiple patterns: mesangial proliferative, membranous, membranoproliferative, endocapillary proliferative, and crescentic forms. Clinically presents with nephrotic syndrome, rapid progression ESRD, and irreversible renal failure .
What are the chances of recurrence of HIVAN post-transplantation?
The risk of recurrence post-transplant is highe if the donor is HIV-infected. The risk of recurrence is low if HIV infection is well controlled by medication References: Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1; 105(7): 1492–1501.
Please counsel this patient discussing the pros and cons of transplantation.
I will counsel him on the following points:
Firstly, & most importantly, that HIV itself is not a contraindication for kidney transplantation (1B), & that transplantation has morbidity & mortality benefits, though associated with increased rate of DGF and rejection as compared to ESRD due to other causes.
Secondly, that being HIV-positive, he will be wait-listed only if he is fulfilling the following conditions:
Adherence with treatment prescribed to control the virus (cART therapy).
The CD4+ T cell counts are >100 cells/μL & have been stable during the preceding 3 months.
Undetectable viral load in the last 6 months.
No opportunistic infections have occurred during the last 6 months.
No H/O progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
Will you elaborate more on HIVAN?
HIVAN is most prevalent in patients who receive ART late after initial diagnosis, & is a major cause for CKD in developing countries. Organ failure develops more quickly than in high income nations due to high incidence of infection-related nephropathies & a lack of secondary preventative measures.
Regardless of the method of HIV transmission, classic HIVAN, as it was first defined in the pre-ART period, continues to occur among ART-naive or non-adherent patients, typically of African heritage.
High viral load, low CD-4 count, & apoliprotein-L1 (APOL1) genetic variant have all been associated with an increased clinical risk for developing HIVAN in the native kidneys of HIV positive individuals.
Proteinuria in the nephrotic range, increased renal echogenicity on US, & a kidney biopsy are used to confirm the diagnosis.
HIV positive patients also suffer from CKD secondary to non-communicable diseases (DM & HTN).
HIV-related CKD has become the third most common cause of ESRD in young people of African descent in the US.
Podocytopathy or immune complex-mediated glomerular disease are two common manifestations of HIV in the kidney. The podocytopathy can manifest as FSGS or MCD & diffuse mesangial hypercellularity.
In 2008, an HIV-positive donor transplant program was launched in South Africa.
For around 20 years, TX programs in the USA have used HIV-negative donors, & more recently, the Hope Act has allowed for the use of HIV-positive donors as well.
In most centers HIV positive patients had been transplanted with HIV negative living & DD. Only one centre had reported long-term outcomes using HIV positive DD with several new centers now embarking on this practice as part of the HOPE act in the USA as well as some centers in Europe.
Specific infection screening considerations in HIV positive TX HPV screening post transplantation:
Post-TX IS may make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection.
Prophylactic therapy:
Life long prophylaxis against PCP.
3 months prophylaxis against CMV if donor positive & recipient negative.
Vaccinations prior to transplant:
Pneumococcal vaccine given to all patients on the waiting list pre-TX.
HBV & HAV vaccination.
Influenza vaccine once yearly.
HZV vaccination in high-risk patients (>50 years old).
HPV vaccination.
All patients have to be up to date with DPT & MMR vaccinations before transplantation.
Vaccinations post-transplant:
Annual influenza vaccination is recommended.
Use of live virus vaccine not recommended (MMR should not be given post-transplant)
It is recommended to wait 3 to 6 months after transplant before giving vaccines.
If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment.
What are the chances of recurrence of HIVAN post-transplantation?
Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence.
HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients.
Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney.
Please counsel this patient in discussing the pros and cons of transplantation.
Advantages (pro) kidney transplantation
Better quality of life
Better patient survival compared to dialysis (less morbidity and mortality especially pertaining to the cardiovascular ds)
Generate more income
Higher rate of fertility
Disadvantages
Higher risk of infection
Higher risk of rejection
Drug interaction
Will you elaborate more on HIVAN?
Classically manifested by focal segmental glomerulosclerosis (collapsing). Patient with HIVAN will experience proteinuria and rapidly worsening renal function. Anti-retroviral therapy is the mainstay of therapy (1).
What are the chances of recurrence of HIVAN post-transplantation?
Recurrence post-transplant is low but compared to non-HIV individual there are at higher rate of acute rejection (2).
Reference
Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
Waheed, S., Sakr, A., Chheda, N. D., Lucas, G. M., Estrella, M., Fine, D. M., & Atta, M. G. (2015).Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLOS ONE, 10(6), e0129702.https://doi.org/10.1371/journal.pone.0129702
Q1:
Pros:
good survival for graft and patient, especially in compared with remaining on waiting list. In addition, the quality of life would be better, too.
Cons:
The higher rate of infection, malignancy, DGF, rejection and drug interactions.
Q2:
HIV-associated nephropathy (HIVAN) starts with proteinuria and could proceed to ESKD. Risk factors are high viral load, low CD4, APOL1 mutations (especially in blacks), but have been reported in Caucasians, too.
Glomerular nephropathy: are usually developed by immune complex.
Tubulointerstitial nephropathy: is related to the treatment of HIV by drugs and opportunistic infections.
Vascular NP: TMA and atherosclerosis or age-dependent nephrosclerosis.
Treatment includes effective HIV treatment and starting ACEi or ARBs or even steroids if needed.
Q3: In one study from the Paris, no recurrence of HIVAN after kidney transplantation, among 27 recipients was noted.
Reference:
1.Blumberg, E. A., & Rogers, C. C. (2019). Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation, 33(9). https://doi.org/10.1111/ctr.13499
2.Touzot, M., Pillebout, E., Matignon, M., Tricot, L., Viard, J. P., Rondeau, E., Legendre, C., Glotz, D., Delahousse, M., Lang, P., & Peraldi, M. N. (2010). Renal transplantation in HIV-infected patients: The Paris experience. American Journal of Transplantation, 10(10). https://doi.org/10.1111/j.1600-6143.2010.03258.x
HIV infection is not contraindications for renal transplantation . discussing the pros and cons of transplantation.
Kidney patient due to hiv infection have better survival with transplantation,better life by getting of hemodialysis,however have more complication compare to non hiv patients due to the use of strong immunosuppressi agent which may activate the virus ore make it stronger .
Will you elaborate more on HIVAN?
No.
What are the chances of recurrence of HIVAN post-transplantation?
The patient is a known case of CKD…he is HIV positive…He needs live related renal transplant…Even in those individuals with HIV there is a survival advantage of those who are on dialysis…There is overall mortality benefit for those after transplant as compared to dialysis and HIV…..
The pros are cART availability has made it possible for transplantation as a viable treatment option for HIV positive patient….They need to fulfill few criteria before transplant like absence of HIV resistance, absence of few oppurtunistic infections like PML, cyrptosporidiosis, no active TB, CD4 count>200 for 6 months, negative HIV RNA viral load for 3 months… There is definitive survival advantage after transplant in HIV individuals..There are studies to show that oppurtunistic infections encountered post transplant in HIV positive patients are not higher than HIV negative individuals….Even on cadaver list the waiting time of HIV positive recipient
The patients who have developed HIVAN and are on dialysis have few points of concern before transplantation…There has been increased reports on rejection and delayed graft function in the population….There is a concern of increased risk of oppurtunistic infection and malignancy in HIV individuals and IL2 receptor antagonists are better choice as compared to the ATG…Older HIV individuals with diabetes are known to have poor graft function as compared to younger HIV individuals….There is also increased drug interaction reported with cART and immunosuppressive agents…
Elaboration on HIVAN:
HIV associated nephropathy is the first kidney disease diagnosed in patients with HIV infected patients….The original description is of nephrotic syndrome having collapsing type of FSGS which leads to CKD and dialysis… HIVAN is more common (50-60 times) in African American individuals..The incidence is more common in individuals with HIV viral load >400 copies/ml, proteinuria > 3 gm/day, CD4 count <200 cells/cumm. The risk of HIVAN is more in individuals with APOL 1 gene with 2 allele….They will present with azotaemia…They will not usually have edema and hypertension….Patients with HIVAN will progress rapidly to CKD and ESRD…urine routine will show nephrotic range proteinuria and hematuria….Kidney biopsy shows collapsing FSGS..Other biopsy features reported with HIV are interstitial nephritis, pseudocrescents, endothelial tubulo reticular interactions and tubular microcystic dilatation….Steroids are used to control the proteinuria and interstitial inflammation….
There is no correlation between the HIV Viral load and recurrence of HIVAN after renal transplant….There are reports of recurrence of HIVAN if the donor has high viral load and not adequately treated before a live or cadaver transplant…Collapsing FSGS has shown to have a high recurrence if the virus is housed in the podocyte..Other forms of HIVAN like proliferative GN and Chronic interstitial nephritis are not known to recur…If the HIV is well managed with cART the chances of recurrence are low…The bottomline is good HAART therapy will keep the viral load under control and reduce the recurrence..HIVAN recurrence has not been reported in US clinical trials
Please counsel this patient discussing the pros and cons of transplantation.
PROS – Increased life span perspective – Leaving hemodialysis CONS – Risk of transplant-related complications: opportunistic infections – increase in the number of medications – polypharmacy
Will you elaborate more on HIVAN?
Clinically, it presents with progressive azotemia, significant proteinuria and little or no peripheral edema in patients with advanced HIV disease. Renal parenchymal injury is characterized by epithelial cell proliferation, dedifferentiation and apoptosis along the entire nephron. Histologically, it is distinguished by finding collapsing glomerulopathy, microcystic tubular dilation, interstitial inflammation and fibrosis.
What are the chances of recurrence of HIVAN post-transplantation?
African studies indicate that this risk is low.
REFERENCE:
Gilbert J, Manji A. Considerations in the Management of a Kidney Transplant Patient With HIV. Cureus. 2021 Oct 13;13(10):e18744. doi: 10.7759/cureus.18744. PMID: 34659933; PMCID: PMC8513352.
Botha J, Fabian J, Etheredge H, Conradie F, Tiemessen CT. HIV and Solid Organ Transplantation: Where Are we Now. Curr HIV/AIDS Rep. 2019 Oct;16(5):404-413. doi: 10.1007/s11904-019-00460-7. PMID: 31482298; PMCID: PMC6813753.
1. Please counsel this patient discussing the pros and cons of transplantation. Kidney transplant even for HIV+ recipients, offers · Better quality of life and Survival benefit compared to HD · But risk of DGF, rejection is increased, as is isk of opportunistic infection and malignancy. HIV-associated nephropathy (HIVAN) · is the most severe form of CKD; commonest cause of ESRD in HIV-positive patients in the UK · Patients are typically young (mean 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure. The majority of patients progress to ESRD within 10 years of diagnosis of HIVAN · Kidney transplantation in HIV-positive patients is complicated by a high rate of acute allograft rejection · Immunosuppression has been well tolerated and HIV viraemia uncommon, although renal complications are relatively frequent. Few patients experience opportunistic infections, HIV disease progression or malignancy. · Most studies suggest that kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise fit and eligible, with life expectancy >5 years. · HAART / cART has improved survival in patients with HIVAN in addition to decreasing the incidence of HIVAN in PLHIV and reducing the risk for progression to RRT · Currently it is recommended to initiate cART in patients with HIVAN, regardless of CD4 cell count · Graft rejection is also a major concern in this population, due to immune dysregulation and the drug interactions between ART and CNI · Counselling the patient about the disease and need for taking HARTT to keep HIV controlled (viral load <50 copies /ml or undetectable). · The patient needs to know that HIVAN could recur in the transplanted kidney. 2. Will you elaborate more on HIVAN? It causes glomerular disease with collapsing FSGN and nephrotic syndrome with heavy proteinuria. The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function, even in the absence of oedema. Biopsy with E/M shows subendothelial tubule-reticualr inclusion bodies, not 100% specific / sensitive. The prognosis in patients with HIVAN is poor, even among those treated with antiretroviral therapy More common in African population. In studies of adult and pediatric people with HIV, 96-100% were African descent. According to data from the (USRDS), more than 85 % of new (ESKD) cases attributed to HIVAN occur in African Americans. In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
Study compared patients with non-HIVAN ESKD and patients with HIVAN ESKD found that the latter had increased mortality Proper donor selection – rule out proteinuria, may need biopsy. What are the chances of recurrence of HIVAN post-transplantation? There is a risk of HIVAN recurrence in the graft post-transplantation, particularly in cases wherein the donor is HIV positive Reported in 23.5% of cases with 3% graft loss according to south African study. References: 1. HIV-Associated Nephropathy in 2022 2. British Transplantation Society Guidelines 3. Winston JA et al; Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344;1979
HIVAN
IT IS cause glomerular disease with collapsing FSGN and nephrotic syndrom with heavy proteinura . which is more more common in african population . biopsy showed E/M it presents with subendothelial tubuloreticualr inclusion bodies.
This condition need counseling the patient about the disease ,and if the patient want to do kidney transplant he has to take the HARTT first and keep HIV PCR COPIES BELOW 50, ADDING TO THAT , proper donor selection ,he has to know that RTX survival is better than to remain odn dialysis.
The patient need to know that HIVAN could recur in the transplanted kidney.
references
uptodate
Pros:
Better quality of life
Survival benefit compared to HD
Cons:
Increased risk of DGF
Increased risk of opportunistic infection and malignancy
Increased risk of rejection Will you elaborate more on HIVAN? HIVAN is classic renal manifestation of HIV but incidence had decreased due to HAART. Patients usually have low CD4 count and increased viral load. Patients have nephrotic syndrome with rapid rise of serum creatinine and histopathology shows collapsing variant of FSGS. Predominantly affects patients of African ancestry due to APOL1 risk alleles. HAART slows the progression. Recurrence: HIVAN is a secondary form of FSGS, if HIV infection is managed well with cART, the chances of recurrence are low.
Please counsel this patient discussing the pros and cons of transplantation.
· HIV-associated nephropathy (HIVAN) is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK
· Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure.
· The majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
· Kidney transplantation in HIV-positive patients is complicated by a high rate of acute allograft rejection
· Immunosuppression appears to be well tolerated, with few patients experiencing opportunistic infections, HIV disease progression or malignancy.
· Immunosuppression has been well tolerated and HIV viraemia uncommon, although renal complications are relatively frequent
· Most studies suggest that kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible.
· cART has dramatically improved survival in patients with HIVAN in addition to decreasing the incidence of HIVAN in PLHIV and reducing the risk for progression to RRT
· Currently it is recommended to initiate cART in patients with HIVAN, regardless of CD4 cell count
· Graft rejection is also a major concern in this population, given the baseline immune dysregulation and the drug interactions between cART and calcineurin inhibitors Will you elaborate more on HIVAN?
· The prognosis in patients with HIVAN is poor, even among those treated with antiretroviral therapy
· The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function, even in the absence of edema.
· HIVAN displays a striking racial predilection for individuals of African descent. In studies of adult and pediatric people with HIV, 96 to 100 percent were of African descent.
· According to data from the (USRDS), more than 85 % of new (ESKD) cases attributed to HIVAN occur in African Americans.
· In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
· A study compared patients with non-HIVAN ESKD and patients with HIVAN ESKD found that the latter had increased mortality What are the chances of recurrence of HIVAN post-transplantation?
· There is a risk of HIVAN recurrence in the graft post-transplantation, particularly in cases wherein the donor is HIV positive
Kidney transplant is a valid choice in HIVAN WITH ESRD
ADVANCTAGES
better than dialysis
effective CART make organ transplant possible in HIV
DISADVANTAGES
increase risk of acute and delayed rejection
Increase risk of drug drug interactions
Increase risk of infections
Increase risk of malignancy
HIVAN – it a type of collapsing FSGN with nephrotic grade proteinuria , normal size echogenic kidney on USG seen in HIV patients with characteristic biopsy findings like microcyst
HIVAN can recur post kidney transplantation
in African American population
Please counsel this patient discussing the pros and cons of transplantation.
The patient should know the following recommendations of British Transplantation Society Guidelines kidney and pancreas transplantation in patients with HIV
All potential kidney transplant recipients are screened for HIV infection
• HIV per se is not a contraindication for kidney transplantation
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication.
Pros
more reliable than on being on dialysis
Cost effective
availability of cART has made it feasible to offer kidney transplantation to HIV-positive patients
Cons
increase risk of acute and delayed rejection
Increase risk of drug drug interactions
Increase risk of infections
Increase risk of malignancy
Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN) is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK (7). Patients of black ethnicity, who constitute one third of those diagnosed with HIV in the UK, are at increased risk of ESRD (7,9,10). Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median estimated glomerular filtration rate [eGFR] 21 mL/min/1.73m2 ) at diagnosis (11). Although suppression of HIV replication may improve or stabilise kidney function, the majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
The podocytopathy can manifest as focal segmental glomerulosclerosis (FSGS) or minimal change disease and diffuse mesangial hypercellularity
Classic HIVAN, as originally described in the pre-ART era continues to occur among ART-naïve or non-adherent patients, usually of African descent, irrespective of the mode of HIV transmission. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV positive patients. Diagnosis is confirmed by a nephrotic range proteinuria, and increased renal echogenicity on ultrasound and a kidney biopsy.28
Pathologically HIVAN is defined by a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy.Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features.
Tubulointerstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease. It accounts for marked kidney enlargement and hyperechoic appearance by ultrasound. Typical tubulointerstitial features include tubular microcysts,” which are dilated tubules (at least 3-fold the diameter of normal tubules) containing glassy proteinaceous casts lined by flattened, simplified epithelium. The microcysts may be focal or diffuse and may involve cortex and medulla, including proximal, distal and collecting tubular segments.
What are the chances of recurrence of HIVAN post-transplantation?
HIVAN recurrence is a concern in some HIV positive transplant programs. In the South African group features of HIVAN presented many years after the transplant and had a slow progression having no clinical impact in most cases.
HIV patients without VL and no CI can be considered for transplantation. Pros.
Better QLF.
Better survival in comparison to HD./PD.
Cost effective in the long term compared to dialysis.
Cons.
Risk of DGF.
2-3-fold increased risk of graft rejection with comparison to non-HIV.
Increased risk of infection particularly with use of lymphocyte depleting agents like ATG.
Polypharmacy with more possibility of drug-to-drug interaction.
More costly due to close monitoring
-HIVAN:
. Collapsing FSGS with tubular dilatation and interstitial inflammation. HIVAN entails HIV infecting epithelial cells and expression of HIV gene in susceptible patients. Genetics is important in etiopathogenesis as proved by increased incidences in APOL1 gene polymorphisms and in Africans.
Presentation is with proteinuria, hardly any edema, +/- hematuria and later renal functions deterioration.
Diagnosis: HIV +VE, CD4 <200, impaired renal function tests, proteinuria, hematuria, collapsing FSGS & commonly normal sized kidneys on US.
Transplantation includes HAART, ACEI/ARBS for HTN and proteinuria, RRT, and SGLT2 inhibitors for proteinuria.
Recurrence of HIVAN
Reported in 23.5% of cases with 3% graft loss according to south African study.
Ref:
Winston JA et al; Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344;1979
HIVAN
IT IS cause glomerular disease with collapsing FSGN and nephrotic syndrom with heavy proteinura . which is more more common in african population . biopsy showed E/M it presents with subendothelial tubuloreticualr inclusion bodies.
This condition need counseling the patient about the disease ,and if the patient want to do kidney transplant he has to take the HARTT first and keep HIV PCR COPIES BELOW 50, ADDING TO THAT , proper donor selection ,he has to know that RTX survival is better than to remain odn dialysis.
The patient need to know that HIVAN could recur in the transplanted kidney.
first patient has to know that renal transplantation is not contraindicated as long as the HIV disease is controlled.
the key of success of he procedure is compliance on antiviral treatment
proper donor selection is mandatory
the survival benefit is less than those without HIV , but much better than maintaining on diaysis.
· Associated with higher rate of bacterial infection especially with ATG, higher rate of DGF and 2 folds of rejection episodes.
2- HIVAN:
It is 2ry FSGS which present clinically with heavy nephrotic syndrome and rapid deterioration of kidney function
HIVAN is 50 times more in African americans with high viral load and presence of APOL1 allels.
diagnosis requires biopsy and typically presents with collapsing subtype focal segmental glomerulosclerosis and microcyst formation in the tubulointerstitial region. E/M it presents with subendothelial tubuloreticualr inclusion bodies.
Treatment :
HAART.
ACEI/ARBS for proteinuria.
renal replacement therapy
SGLT2 inhibitors for proteinuria
3- Recurrence: is expected if viral load is not controlled.
5. A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
– HIV positive patients are more susceptible to kidney disease than their HIV negative counterparts so kidney transplantation does not entirely absolve them from kidney issues
– this is due to the direct impact of the HIV virus on the kidney as well as the associated immune response
Pros of kidney transplantation
– kidney transplantation is the best treatment modality for ESKD patients
– no need for dialysis
– better quality of life
– shorter waiting time
Cons of kidney transplantation
– major surgery with potential risk
– risk of infections and malignancies following kidney transplant
– risk of delayed graft function
– risk of rejection
– lifelong immunosuppressive drugs
– drug-drug interactions between HAART and the immunosuppressive drugs
– risk of HIVAN recurrence in the graft kidney
Will you elaborate more on HIVAN?
– HIVAN is described as the classic kidney disease commonly associated with HIV infection (1)
– histologically, it is a collapsing form of FSGS accompanied by microcystic tubular dilatation and interstitial inflammation (2)
– Pathogenesis: HIV directly infects glomerular and kidney tubular epithelial cells with subsequent expression of HIV genes within the infected kidney cells in a genetically susceptible host (3)
high index of suspicion in a patient with CD4 <200, HIV viremia, nonadherence to HAART, nephrotic-range proteinuria, rapidly declining kidney function even in the absence of edema
a kidney biopsy is required to establish a definitive diagnosis f HIVAN
patients suspected to have HIVAN based on the clinical presentation may have a different histologic diagnosis e.g., classical FSGS, MPGN, DKD, lupus-like immune complex GN, amyloidosis
– Differential diagnosis: noncollapsing FSGS, immune complex-mediated GN (IgA, MN, MPGN, lupus-like proliferative GN), GN due to HBV or HCV co-infection, DKD, amyloidosis (7)
– Treatment – no RCTs have been done to evaluate the therapies listed below:
if HAART naïve, initiate HAART otherwise assess medication adherence, drug resistance
HAART regimen should be dose adjusted for kidney function
RAASi (ACEi/ ARBs) for patients with proteinuria and/ or hypertension, if proteinuria persists add on SGLT2i
SGLT2i have been shown to slow progression of non-diabetic proteinuric CKD including FSGS
generally, there is no role for routine glucocorticoids in HIVAN
for patients with no improvement in kidney function, glucocorticoids can be considered after weighing benefits vs risk – risk of infection, metabolic derangements
some studies suggest that glucocorticoids improve kidney function and reduce proteinuria in HIVAN patients (8)
monitor response to treatment using sCR, eGFR, uPCR or uACR, CD4, HIV viral load
some HIVAN patients eventually progress to ESKD and should be well prepared for dialysis and transplantation
– Prognosis: remains poor even among those on HAART, many
such patients progress to ESKD
What are the chances of recurrence of HIVAN post-transplantation?
– HIVAN recurrence is a major concern, requires more attention in the future References
1. Gardenswartz MH, Lerner CW, Seligson GR, Zabetakis PM, Rotterdam H, Tapper ML, et al. Renal disease in patients with AIDS: a clinicopathologic study. Clinical nephrology. 1984 Apr;21(4):197-204. PubMed PMID: 6733986. Epub 1984/04/01. eng.
2. Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int. 1999 Dec;56(6):2203-13. PubMed PMID: 10594796. Epub 1999/12/14. eng.
3. Bruggeman LA, Ross MD, Tanji N, Cara A, Dikman S, Gordon RE, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. Journal of the American Society of Nephrology : JASN. 2000 Nov;11(11):2079-87. PubMed PMID: 11053484. Epub 2000/10/29. eng.
4. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. Journal of the American Society of Nephrology : JASN. 2011 Nov;22(11):2129-37. PubMed PMID: 21997394. Pubmed Central PMCID: PMC3231787. Epub 2011/10/15. eng.
5. Kudose S, Santoriello D, Bomback AS, Stokes MB, Batal I, Markowitz GS, et al. The spectrum of kidney biopsy findings in HIV-infected patients in the modern era. Kidney Int. 2020 May;97(5):1006-16. PubMed PMID: 32278618. Epub 2020/04/13. eng.
6. Bigé N, Lanternier F, Viard JP, Kamgang P, Daugas E, Elie C, et al. Presentation of HIV-associated nephropathy and outcome in HAART-treated patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2012 Mar;27(3):1114-21. PubMed PMID: 21745806. Epub 2011/07/13. eng.
7. Atta MG, Choi MJ, Longenecker JC, Haymart M, Wu J, Nagajothi N, et al. Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. The American journal of medicine. 2005 Nov;118(11):1288. PubMed PMID: 16271919. Epub 2005/11/08. eng.
8. Eustace JA, Nuermberger E, Choi M, Scheel PJ, Jr., Moore R, Briggs WA. Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids. Kidney Int. 2000 Sep;58(3):1253-60. PubMed PMID: 10972688. Epub 2000/09/06. eng.
Please counsel this patient discussing the pros and cons of transplantation.
Pros of transplantation in a patient on dialysis include:
· Better quality of life and patient survival
· Risk of HIV viremia is low if the patient fulfilling specific criteria and well controlled on HAART
· Risk of HIVAN post transplant is low if viremia controlled on HAART.
· Rate of opportunistic infection not significantly higher than non HIV recipient Cons of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
· Higher rate of rejection
· Some immunosuppresions have greater risk of HIV activation and better to be avoided
· Some HAART medications interact with immunosuppresions and to be modified.
· Maliganacy is higher especially with human papilloma virus
Will you elaborate more on HIVAN?
HIVAN is 2ry form of FSGS which present clinically with heavy nephrotic syndrome and dearranged kidney functions with rapid deterioration of eGFR
HIVAN is 50 times more in African americans with high viral load and presence of APOL1 allels.
In L/M its usually presents with picture of collapsing FSGS and E/M it presents with subendothelial tubuloreticualr inclusion bodies.
management include conservative management include ACEI or ARBS,statins, steroids and cART.
What are the chances of recurrence of HIVAN post-transplantation?
Its 2ry FSGS related to HIV.multicenter study done is US showed low rate of recurrence post transplant if the patient fullfiling specific criteria pretransplant with good compliance on cART post transplant. References:
Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
Lucas A, Wyatt CM. HIV at 40: kidney disease in HIV treatment, prevention, and cure. Kidney Int. 2022 Oct;102(4):740-749. doi: 10.1016/j.kint.2022.06.021. Epub 2022 Jul 16. PMID: 35850290; PMCID: PMC9509437.
Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11. doi: 10.1159/000526868. PMID: 36816427; PMCID: PMC9936764.
Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA, Atta MG. HIV-associated nephropathy: links, risks and management. HIV AIDS (Auckl). 2018 May 25;10:73-81. doi: 10.2147/HIV.S141978. PMID: 29872351; PMCID: PMC5975615.
Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, Viard JP, Anglicheau D, Bienaimé F, Muorah M, Galmiche L, Gribouval O, Noël LH, Satie AP, Martinez F, Sberro-Soussan R, Scemla A, Gubler MC, Friedlander G, Antignac C, Timsit MO, Onetti Muda A, Terzi F, Rouzioux C, Legendre C. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014 Feb;25(2):407-19. doi: 10.1681/ASN.2013050564. Epub 2013 Dec 5. PMID: 24309185; PMCID: PMC3904571.
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. Please counsel this patient discussing the pros and cons of transplantation.
-HIV pts with undetectable VL and no other CI to transplant should all be considered for renal transplantation. The HOPE treaty allows HIV pts to enroll as donors.
Pros;
Better quality of life.
Has a survival benefit in comparison to HD./PD.
Cheaper in the long term compared to HD./PD.
Cons;
Increased risk of DGF.
X2-3 risk of graft rejection in comparison to non HIV popn.
Increased risk of infection esp with lympocyte depleting agents like ATG.
Polypharmacy with more drug to drug interaction.
More costly to monitor esp the OIs ,SE and DI in comparison to non HIV popn.
Will you elaborate more on HIVAN?
Classic renal dx from HIV is a collapsing FSGS with tubular dilatation and interstitial inflammation. HIVAN involves HIV infecting epithelial cells with expression of HIV gene in susceptible individuals. Genetics play a key role in pathogenesis as evidenced by increased incidences in APOL1 gene polymorphisms and Africans.
These pts will present with proteinuria, most have normal BPS, hardly any edema,+/- hematuria and later dev renal functions derangements.
Diagnosis is evidenced by HIV +VE,CD4 <200,deranged renal function tests, proteinuria, hematuria, collapsing FSGS and most have normal sized kidneys on US.
TX involves;
HAART.
ACEI/ARBS in HTN and those with proteinuria.
RRT – HD/PD/transplantation.
SGLT2 inhibitors for proteinuria as evidenced or an extrapolation for DAPA CKD study.
HIVAN Recurrence;
-A south African study involving 51 KTR had 23.5% of pts with recurrence of nephropathy and 3% graft loss. All those with nephropathy had suppressed VL during the study.
REF;
Winston JA et al; Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344;1979
Gardenswatz MH et al ; Renal dx in pts with AIDS;A clinicopathologic study.Clin Nephrol;1984;21;197
Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplantation is the best treatment option for the eligible patient with ESRD regardless of their HIV status.
Pros
It is associated with better quality of life and survival rates than being on dialysis.
It is more cost effective than dialysis.
Cons
There are strict criteria that one has to fulfil to make you eligible.
There is increased risk of infections and malignancy hence need of prophylaxis medications that may increase ones pill burden.
There is an increased risk of rejection this could be due to drug interactions between the ART and immunosuppressive medication.
There is a higher rate of DGF in the HIV population hence one might be on dialysis briefly after transplantation.
Will you elaborate more on HIVAN?
HIVAN is the classic kidney disease of HIV infection however its incidence has been declining with the use of cART.
It presents usually in the patient with a low CD4 counts and high viral loads with heavy proteinuria, rapidly rising Scr and histopathological findings of collapsing glomerulosclerosis and tubulointerstial inflammation.
It predominantly affects persons of African ancestry due to the predominance of the APOL1 risk alleles.
Use of cART can prevent it and reverse it.
Treatment involves initiation of cART in the ART naive patient, blockade of the RAAS, steroids and RRT
What are the chances of recurrence of HIVAN post-transplantation?
A south African study where 51 patients were followed up for 10 year period, 12 patients had features of HIVAN on per protocol biopsy with only 2 of them who lost their graft.
Further research is thus required.
References
HIV-Associated Nephropathy in 2022
Rivera F.B.a, Ansay M.F.M.b, Golbin J.M.c, Alfonso P.G.I.c, Mangubat G.F.E.d , Menghrajani R.H.S.e, Placino S.e,Taliño M.K.V.b, De Luna D.V.f, Cabrera N.g, Trinidad C.N.h, Kazory A.i
HIV-associated nephropathy: links, risks and management
Laura Palau, Steven Menez, […], and Mohamed G Atta
Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies
Elmi Muller, MD PhD, Francois C. J. Botha, MBChB, […], and Peter Stock, MD PhD
Kidney transplantation is the best RRT option, irrespective of the HIV status of the recipient. The pros of transplantation include:
1. better survival rates.
2. better quality of life.
3. Because of the availability of cART, transplantation is now a viable treatment option for HIV-positive patients who meet certain criteria.
4.waiting time on the waitlist may be reduced by the option of HIV-positive donor acceptance.
Kidney transplantation is the best RRT option, irrespective HIV status of the recipient.
The cons of transplantation include:
1- increased rates of rejection & DGF if compared to the general population.
2- drug interactions should be considered & monitored closely.
3- increased risk of infection & malignancy post-transplantation
4-incidence of HPV-mediated cancers
5- the risk of HIVAN recurrence was reported
Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN)can present by nephrotic syndrome (with a collapsing FSGS), rapid progression to ESRD.
– HIVAN risk is 50 times higher in African-Americans than in whites, and the existence of 2 APOL1 risk alleles increases the risk. -clinical picture:
1- CD4 count of 200, a high viral load (>400 copies/ml).
2- proteinuria, Edema and hypertension .
3- high s.creatinie
4- renal biopsy: characterized by FSGS collapse, interstitial nephritis, visceral epithelial cell proliferation.Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features. -management:
1- cART (independent of CD4 count).
2-anti proteinuric measures ( low salt diet, bl.p control, ACEI or ARBS , diuretics)
3-CKD management, with RRT options with priority of transplanatation
What are the chances of recurrence of HIVAN post-transplantation?
-HIVAN recurrence is concern. conclosions from Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies Muller, Elmi MD, PhD1; Botha, Francois C. J. MBChB2; Barday, Zunaid A. MBChB3; Manning, Kathryn MPH1; Chin-Hong, Peter MD, PhD4; Stock, Peter MD, PhD5
-HIVAN symptoms appeared many years after the transplant in the South African group and progressed slowly without clinical significance. In the 51 South African transplants, 12 patients had HIVAN-related biopsy abnormalities, although only 2 lost their grafts. These patients experienced rejection in the first three years following transplantation.
-All HIVAN recurrence patients had undetectable viral levels throughout the investigation. This study observed no link between donor viral load and HIVAN recurrence.
-HIVAN occurred in 2 of 150 HIV-positive individuals in a US multicenter trial.
-HIVAN recurrence must be addressed in the future.
-Canaud et al.47 report rapid graft function decline after HIVAN diagnosis in the podocyte rather than the tubular cell of the transplanted kidney. Canaud et al. found a significant rate of HIV infection in transplanted kidneys, but the US trial did not (source NEJM). Future research will investigate these discrepancies.
– Aggressive immunosuppression to treat rejection may cause a kidney viral reservoir flare-up.
Please counsel this patient discussing the pros and cons of transplantation.
Pros of transplantation include:
Kidney transplantation is the best treatment for end stage renal disease, even for HIV patients, because dialysis does not replace all the functions of a kidney.
Kidney transplantation from donors without HIV is very safe and even kidneys from those with HIV to people living with both HIV and end-stage kidney disease is feasible and relatively safe. Getting a kidney from an HIV positive donor may reduce waiting time for a transplant.
Medicines are now available to fight HIV as well as the infections that may occur in transplant patients.
Cons of transplantation include:
Kidneys transplanted into HIV patients may not work as well as those who do not have the virus.
Powerful medications may have to be used to prevent rejection of the donated kidney; but these drugs can lead to the rise of HIV and other infections which then would require anti-viral medications and anti-biotics.
Some anti-rejection medications react with anti-viral medicines, making the treatment choice difficult at such occasions.
Patients with HIV getting anti-rejection medications for transplanted kidneys may sometimes develop cancers more frequently than those without HIV.
Will you elaborate more on HIVAN?
Clinical Features: HIV-infected patients may present at any age with HIVAN, which is a collapsing form of FSGS. Usual findings are nephrotic syndrome, progressively increasing serum creatinine at presentation, and rapid progression, with about half reaching ESRD within 3 years. Edema and hypertension are not typically seen in HIVAN. Patients will have high viral load and low CD4 counts signifying advanced HIV infection. Kidneys are often enlarged in HIVAN patients on ultrasound. A kidney biopsy in needed for confirmatory diagnosis.
Light microscopy: Segmental or global glomerular tuft collapse with overlying visceral epithelial hyperplasia and hypertrophy is seen. Hypertrophied visceral epithelial cells have frequent protein droplets. There is accompanying microcystic tubular dilatation and active tubulointerstitial nephritis with a predominantly lymphocytic infiltrate, often with tubulitis and edema.
Immunofluorescence microscopy: No or limited immune deposits (nonspecific IgM and C3 staining in collapsed segments) are identified. .
Electron microscopy: Glomerular basement membranes are wrinkled and collapsed. Overlying visceral epithelial cells show hypertrophy and hyperplasia, with frequent vacuoles and protein droplets. There is extensive foot process effacement and no or limited mesangial deposits. Tubuloreticular aggregates are present in endothelial cells.
The prevalence of HIVAN among HIV-infected individuals has decreased dramatically since the advent of combination antiretroviral therapy (cART).
Differential Diagnosis: Collapsing glomerulopathy can be related to other infections (eg, parvovirus), drugs (eg, bisphosphonates and calcineurin inhibitors), thrombotic microangiopathy or systemic lupus erythematosus.
History of HIV infection and the presence of tubuloreticular aggregates indicate HIVAN as the etiology of the collapsing lesions. Management: Initiation of cART , ACE inhibitors or ARBs, and steroids (to reduce tubulointerstitial inflammation). Dialysis is initiated in case ESRD develops and transplantation is an option. Renal transplant should be offered if the patient fulfils certain criteria like CD4 count >200 and undetectable viral load by PCR.
What are the chances of recurrence of HIVAN post-transplantation?
In a study 64% patients developed delayed graft function (DGF), and 54% patients required post-operative dialysis within one week of transplant. Graft survival rates at 1 and 3 years were 100% and 81%, respectively. Acute rejection rates at 1 and 3 years were 18% and 27%, respectively. If HIV infection is managed well with cART, the chances of recurrence are low. References:
Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(9): e96-138.
British Transplantation Society. Kidney and Pancreas Transplantation in patients with HIV, 2nd ed.; British Transplantation Society: Macclesfield, UK, 2017
Please counsel this patient discussing the pros and cons of transplantation
Kidney transplantation in the HAART era has shown improved overall survival compared to HIV patients on dialysis, and similar graft survival rates to HIV- negative patients. Due to these encouraging results, HIV-seropositivity is no longer a contraindication to renal transplantation.
Recent studies showed that:
Patient survival was 97% at 1 year and 94% at 3 years.
Graft survival was 91% at 1 year, and 81% at 3 years.
Acute rejection was 33% at 1 year.
Infectious complications occurred in 41% at 1 year.
Above data for the short-term outcome, but data regarding long-term outcomes and comparisons with appropriately matched HIV− patients are
still lacking.
These outcomes are inferior to other transplant recipients without HIV but better than dialysis patients.
Other disadvantages of kidney transplantation in HIV +ve patients is interaction between HAARTs and some immunosuppressive medications. Which means that we need special concentration on these drugs, measure the level whenever available,
Will you elaborate more on HIVAN?
HIV infection can directly cause renal dysfunction in a variety of ways, including HIV-associated nephropathy (HIVAN), immune complex diseases, and thrombotic microangiopathy. HIVAN occurs in approximately 10% of patients with HIV and is the third most common etiology of end-stage renal disease (ESRD) among African Americans aged 20–64 years.
HIVAN is pathologically characterized by a collapsing glomerulopathy with active tubulointerstitial inflammation.
What are the chances of recurrence of HIVAN post-transplantation?
In South African study it occurred in 12 out of 51 cases. However, only 2 cases lost their graft as result of the recurrence.
In American cohort the recurrence was much less in 2 out of 150 cases over 3years.
References;
1-HIV-associated nephropathy: links, risks
and managementHIV/AIDS – Research and Palliative Care 2018:10 73–81.
2-Kidney transplant outcomes in HIV‑positive patients: a systematic review and meta‑analysis, Zheng et al. AIDS Res Ther (2019) 16:37 3- Challenges of kidney transplantation in HIV positive recipients
Mahmoud Alameddine1, Joshua S. Jue2, Ian Zheng1, Gaetano Ciancio1Transl Androl Urol 2019;8(2):148-154
Patient can have a near normal life with ability to do daily activities not their own
Patient can travel anywhere without being tied down to the dialysis center and having to schedule their life around sessions
Fewer restrictions in terms of diet
Better chances of reproduction with return to normal fertility before kidney disease
improved vitality
Cons of kidney transplant
Kidney transplant is a major surgery, and thus risks like bleeding are possible.
Blood transfusion may need to be done.
Strong immunosuppressive medications need to be taken by the patient, because this will reduce the risk of graft rejection. However, even with such medication, it is possible that the patient may lose their graft. The transplant may not be successful. But the transplant team will do everything in their capability to prevent such an incident.
Depending on the disease, kidney damage can occur in the graft also.
Serious life threatening complications are a possibility.
Possible increase in HIV viral load post transplant because of strong immunosuppression and drug interactions between IS drug regimen and ART.
Lifelong medication which the patient has to remember to adhere to.
Patient has to completely stop alcohol, drug abuse, and smoking if he has those habits.
Possibility of diabetes and cancer post transplant due to necessary medications.
HIVAN
HIVAN or HIV associated nephropathy is a complication of AIDS and can occur following acute seroconversion or chronic disease.
Expression of HIV 1 genes in kidney epithelial cells is a pre-requisite for HIVAN to develop. The mechanism of HIV infecting renal epithelial cells is unclear. Classical receptors necessary for entry of virus into T cells and macrophages are absent from renal cells. Studies show that macrophages and lymphocytes appear to be vectors for renal epithelial cell transmission of HIV. Among these are CD209 and DEC205. CD209 antigen mediates HIV infection of dendritic cells. DEC205 antigen contributes directly to infection of renal tubular cells.
Polymorphisms in APOL1 can result in an increased risk of HIVAN. The mechanism of variation is unclear.
Phagocytosois of apoptotic CD4+ T cells could be a possible mechanism by which HIV accesses renal cells.
Histopathology – HIVAN is defined as collapsing glomerulonephropathy and associated tubulointerstitial disease, which includes tubular micro cysts and inflammation of the interstitial. Diffuse effacement of podocyte foot process and endothelial tubular inclusions can be examined by electron microscopy. Staining for IgM, C3 and C1q in collapsed segments and mesangial areas is seen by immunofluorescence.
HIVAN presents with a swift decline in GFR and proteinuria in the nephrotic range.
Differential diagnosis include HIV associated immune complex kidney disease, membranoproliferative GN (co-infection with HCV infection), amyloidosis, minimal change disease, post infectious GN, thrombotic microangiopathy, diabetic nephropathy, immunoglobulin A nephropathy, membranous glomerulopathy.
Before the advent of combined antiretroviral therapy, HIVAN was an aggressive disease that resulted in rapid progression to ESRD in 4 months. Currently, prognosis is better and more favorable for these patients. However, it is crucial to remember that these patients have worse outcomes than other recipients.
Main complication is progression to CKD, and subsequently, ESRD requiring RRT. Other less significant complications include hypertension and lower extremity edema.
Patient should be encouraged and educated to be compliant with ART and to follow up on a regular basis.
Chances of recurrence of HIVAN post transplantation
Cumulative incidence of recurrent IgAN after 7 years post transplant is at a range of 25-30%.
Risk of IgAN recurrence after 11 years is around 27%.
References
NHS blood and transplant. Benefits and risks of a kidney transplant – How a kidney transplant can help and problems that might occur.
Melendez Rivera JG, Hashmi MF. HIV Nephropathy. [Updated 2022 Aug 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559134/
Jäger, C., Stampf, S., Molyneux, K. et al. Recurrence of IgA nephropathy after kidney transplantation: experience from the Swiss transplant cohort study. BMC Nephrol 23, 178 (2022). https://doi.org/10.1186/s12882-022-02802-x
HIVAN recurrence is found to not have much data at present. There is however evidence suggesting that immune complex mediated GN is a significant contributor to kidney disease in the HIV population. Clinical and histological recurrence of HIV associated lupus like nephritis after successful kidney transplantation is rare and causes hematuria, proteinuria and impaired kidney function.
Further studies are needed to accurately assess the rates of HIVAN recurrence after kidney transplant.
Reference
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013 Aug;62(2):335-8. doi: 10.1053/j.ajkd.2013.01.010. Epub 2013 Mar 5. PMID: 23481367; PMCID: PMC4121438.
Please counsel this patient discussing the pros and cons of transplantation.
HIV per se is not a contraindication for kidney transplantation. HIV positive patients should be selected for transplantation according to standard selection criteria, similar to HIV negative transplant recipients. Additional recommendations, include that the patient should be virally suppressed (undetectable viral load) and be on a stable ART regimen for at least 3 months before the date of the transplant. Ideally the patients must have a CD4 count above 200 cells/mm3, but patients with lower CD4 counts have been transplanted successfully in the past.
The transplantation of recipients with low, but detectable levels of HIV remains a contentious issue. Some programs are moving forward with transplantation in this cohort. The majority of clinicians will accept patients for transplantation with a temporary viral load increase that is less than 200cps/ml. Nonetheless, since this may represent low grade replication, transplantation of HIV positive recipients with viral loads less the 200 cps/ml should be limited to centres with a broad experience in the transplantation and management of the HIV infected recipient.
HIV-Associated Nephropathy (HIVAN) is most prevalent in patients who receive antiretroviral therapy (ART) late after initial diagnosis, and is a major cause for CKD.
High rates of infection-related nephropathies and a limited capacity for secondary prevention result in more rapid progression to organ failure . Estimating the burden of CKD in HIV-positive patients is important when considering the allocation of resources including dialysis, availability of deceased and living donor organs, and transplantation.
To know the benefits of transplantation in the HIV infected population.
To know underlying burden of organ failure and its risk factors, irrespective of current treatment availability or eligibility criteria.
Also the improved quality of life and better long-term prognosis of a HIV positive patient, the focus for treatment for these patients have moved to transplantation rather than dialysis over the last 10 years. Will you elaborate more on HIVAN?
HIV-positive individuals is diverse, including lesions directly related to intrarenal HIV gene expression and lesions related to co-morbidities, drug effects, immune dysregulation, and other co-infections . Podocytopathy or immune complex-mediated glomerular disease are two common manifestations of HIV in the kidney.
The podocytopathy can manifest as focal segmental glomerulosclerosis (FSGS) or minimal change disease and diffuse mesangial hypercellularity.
Because of the direct impact of the virus on the kidney as well as the associated immune response, HIV positive patients are more suspectable to CKD than HIV negative patients.. What are the chances of recurrence of HIVAN post-transplantation?
Yes there are chances of HIVAN recurrance, but data is lacking and needs more studies References
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5. . Roland ME, Barin B, Huprikar S, et al. Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS. 2016;30(3):435–44. Doi: 10.1097/QAD.0000000000000934 [PMC free article] [PubMed] [CrossRef] [Google Scholar
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
HIV per se is not a contraindication for kidney transplantation. End stage renal disease 2/2 HIV should be offered transplant if there CD4. count is more than 200 cells/microliter for at least 3 months and the viral load is undetectable for the same period and the patient has. demonstrated compliance and has no active infection and/or malignancy.
HIV-positive patients are wait-listed only if:
a) They are adherence with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma Please counsel this patient discussing the pros and cons of transplantation. Pre-transplant testing and immunization, immunosuppressive protocol, post-transplant prophylaxis, risk of rejection, prognosis, long-term results, post-transplantation problems, HIV infection, and delayed graft function. Kidney Tx. can be successful in HIV+ patients, but further studies are needed to optimize immunosuppressive therapy regimens to reduce AR after transplantation. Kidney transplantation is the treatment of choice for many patients with end-stage kidney disease. A successful kidney transplant can improve your quality of life and reduce your risk of dying. In addition, patients who undergo kidney transplantation do not require hours of dialysis treatment. Ideally, patients who are eligible to get a kidney transplant do so before ever starting on dialysis. Patient selection for HIV positive transplantation HIV positive patients should be selected for transplantation according to standard selection criteria, such as virally suppressed, stable ART regimen, and CD4 count above 200 cells/mm3. However, transplantation of HIV positive recipients with viral loads less than 200 cps/ml should be limited to centres with abroad experience. Patients with fully treated tuberculosis should be considered for transplantation, while those with opportunistic infections and neoplasms without effective medical therapy are excluded. All potential recipients should be screened for tuberculosis, syphilis and hepatitis C pre-transplant. Treatment/screening for co-infection for HBV/HCV should be done prior to transplant. The Pros: Improve your quality of life. The new kidney will help restore the body’s metabolism and improve blood circulation, allowing the body to handle nutrients better and live a healthy life. The Cons: Delayed graft function (DGF), AR, graft loss and days spent hospitalized in the first year after KT as well as a trend towards lower mortality. Acute rejection. Young age, heavy proteinuria before transplant, and rapid progress of primary FSGS are independent risk factors for recurrent FSGS. Infectious complications Drug interaction Will you elaborate more on HIVAN? HIV-related nephropathy is a major cause of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from AKI and CKD. A full virologic cure is only possible with complete eradication of the viral reservoir in the kidney. Renal disease associated with HIV infection is primarily a glomerular dominant disease, classified into two maincategories:podocytopathies and immune complex-mediated disease. Specific infection screening considerations in HIV positive TX HPV screening post transplantation: Post-TX MAY make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection. Secondary causes should be sought in post-infectious glomerulonephritis. HIV-associated nephropathy incidence peaked in the mid-1990s but has declined due to increased use of combined anti-retroviral treatments.
Pathophysiology: HIV-Associated Nephropathy: HIV-Associated Nephropathy is caused by the expression of HIV-1 genes in the kidney epithelial cells, which is mediated via transfer from leukocytes and phagocytosis of apoptotic CD4+ T cells. Polymorphisms in APOL1 result in an increased riskof HIVAN. HIV-Associated Immune Complex Kidney Disease HIV-associated immune complex kidney disease is caused by co-infection with hepatitis B and C, but the mechanism and relevance of post-antiretroviral therapy is unknown. HIV-Associated Thrombotic Microangiopathy Thrombotic microangiopathy is caused by exposure to circulate viral proteins combined with medications, proinflammatory molecules, and antiphospholipid antibodies. Histopathology HIVAN it is the classic kidney disease that has been associated with HIV infection as a complication of AIDS. Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubulo-reticular inclusion bodies, with diffuse effacement of podocyte foot process and endothelial tubular inclusions may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants. Due to the cART, the incidence of HIVAN is declining. Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESRD.
Patients with HIVAN have: Advanced HIV disease with a CD4 of less than 200 Nephrotic range proteinuria Rapid decline in kidney function HIV-associated nephropathy is characterized by collapsing glomerulopathy and tubulointerstitial disease, HIV-related kidney diseases fall under four pathologic classifications: Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases. Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial, or fungal pathogens Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis. Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis. History and Physical: HIV-associated nephropathy is characterized by a rapid decline in GFR and proteinuria, but other manifestations are uncommon. Evaluation: Screening for HIV nephropathy in HIV positive patients should include serum creatinine and estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline when ART is initiated or changed, and at least twice a year in stable patients infected with HIV. Imaging modalities, such as ultrasonography of the kidneys, may be useful in specific settings, but a kidney biopsy is often the only means of achieving a definitive diagnosis. CART induced nephropathy is more common than HIVAN, presenting with CD4 count <200 cells/mm, viral load >400 copies/mL, rapid decline in renal function, proteinuria >300 mg/24h, hyaline or proteinaceous casts on urinalysis, and large-sized kidneys with intense cortical echogenicity. Diagnosis:
The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
Suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
Kidney biopsy is gold standard for diagnosis of HIVAN.
There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease. Differential Diagnosis: Noncollapsing focal segmental glomerulosclerosis (FSGS) HIV-associated immune complex kidney disease Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection) Amyloidosis Minimal change disease Postinfectious glomerulonephritis Thrombotic microangiopathy Diabetic nephropathy Immunoglobulin A nephropathy Membranous glomerulopathy Differential diagnosis Collapsing glomerulopathy:
FSGS primary (idiopathic) FSGS
Parvovirus B19 infection
SV40 infection
acute CMV infection
Erythrophagocytosis syndrome
Interferon therapy
Pamidronate toxicity
Acute vaso-occlusive injury
Rare familial forms Treatment: HIVAN is associated with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, so 1-Combined antiretroviral therapy is the mainstay of treatment for all patients with HIV infection regardless of CD4 count.
It is important to adjust cART therapy to renal function, and renal replacement therapy remains the mainstay. Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs) are also important, and steroids can be added as an adjunct.
SGLT2 inhibitors Prophylactic therapy: Prophylaxis against PCP and CMV is like regimens used at most centers for HIV negative recipients. Vaccinations prior to transplant: Pneumococcal vaccine given to all patients on the waiting list pre-TX. Hepatitis A and B vaccine, if indicated, should be given before the transplant. Influenza vaccine once yearly. HZV vaccination in high-risk patients (>50 years old). HPV vaccine should be given in selected patients, usually under the age of 45 years. All patients must be up to date with DPT & MMR vaccinations before transplantation. Vaccinations post-transplant: Annual influenza vaccination is recommended. Use of live virus vaccine not recommended (MMR should not be given post-transplant) It is recommended to wait 3 to 6 months after transplant before giving vaccines. If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment. Immunosuppression and antiretroviral therapy challenges Interaction between protease and non-nucleoside reverse transcriptase inhibitors with the CNI and mTOR inhibitors. Variable drug levels between patients and often CNI dosages must be significantly increased or decreased because of these drugs on the cytochrome P450 enzyme. Prognosis: The prognosis in patients with HIVAN is poor, even among those treated with ART. HIVAN consistently do worse than those with other causes of renal disease. Many HIVAN patients will develop end-stage kidney disease (ESKD). Complication: HIVAN can lead to CKD, ESRD, hypertension, and lower extremity edema. Deterrence and Patient Education: HIV-associated nephropathy is an aggressive disease that can lead to end-stage renal disease, so patients should be encouraged to be compliant with antiretroviral medications and follow up with their primary care clinician and nephrologist on a regular basis. Pearls and Other Issues Combined antiretroviral therapy is the mainstay treatment for HIVAN, but other aetiologies are more common due to cART and improved survival. An interprofessional team approach should be used to improve patient outcomes, including frequent renal function testing and biopsy. CD4 count and viral load should be considered for cART initiation. What are the chances of recurrence of HIVAN post-transplantation? HIV-positive patients who underwent a second transplant had a 1.96-fold higher risk of allograft loss and a 3.1-fold increased risk of death. The risk of recurrence of collapsing FSGS is approximately 30% after transplantation. Prognosis is poor for HIVAN recurrence after kidney transplantation. Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence. HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients. Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney. Reference HIV and Kidney Transplantation by Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool -UK
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013;62(2):335-338. doi: 10.1053/j.ajkd.2013.01.010
Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int 92: 461–469, 2017
Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018 May;27(3):144-152. Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kathryn Manning, Peter Chin-Hong, Peter Stock, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies, Transplantation. 2021 July 01; 105(7): 1492–1501. doi:10.1097/TP.000000000000 3485.
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation. Please counsel this patient discussing the pros and cons of transplantation. Will you elaborate more on HIVAN? What are the chances of recurrence of HIVAN post-transplantation? HIV per se is not a contraindication for kidney transplantation. End stage renal disease 2/2 HIV should be offered transplant if there CD4. count is more than 200 cells/microliter for at least 3 months and the viral load is undetectable for the same period and the patient has. demonstrated compliance and has no active infection and/or malignancy.
HIV-positive patients are wait-listed only if:
a) They are adherence with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma Please counsel this patient discussing the pros and cons of transplantation. Pre-transplant testing and immunization, immunosuppressive protocol, post-transplant prophylaxis, risk of rejection, prognosis, long-term results, post-transplantation problems, HIV infection, and delayed graft function. Kidney Tx. can be successful in HIV+ patients, but further studies are needed to optimize immunosuppressive therapy regimens to reduce AR after transplantation. Kidney transplantation is the treatment of choice for many patients with end-stage kidney disease. A successful kidney transplant can improve your quality of life and reduce your risk of dying. In addition, patients who undergo kidney transplantation do not require hours of dialysis treatment. Ideally, patients who are eligible to get a kidney transplant do so before ever starting on dialysis. Patient selection for HIV positive transplantation HIV positive patients should be selected for transplantation according to standard selection criteria, such as virally suppressed, stable ART regimen, and CD4 count above 200 cells/mm3. However, transplantation of HIV positive recipients with viral loads less than 200 cps/ml should be limited to centres with abroad experience. Patients with fully treated tuberculosis should be considered for transplantation, while those with opportunistic infections and neoplasms without effective medical therapy are excluded. All potential recipients should be screened for tuberculosis, syphilis and hepatitis C pre-transplant. Treatment/screening for co-infection for HBV/HCV should be done prior to transplant. The Pros: Improve your quality of life. The new kidney will help restore the body’s metabolism and improve blood circulation, allowing the body to handle nutrients better and live a healthy life. The Cons: Delayed graft function (DGF), AR, graft loss and days spent hospitalized in the first year after KT as well as a trend towards lower mortality. Acute rejection. Young age, heavy proteinuria before transplant, and rapid progress of primary FSGS are independent risk factors for recurrent FSGS. Infectious complications Drug interaction Will you elaborate more on HIVAN? HIV-related nephropathy is a major cause of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from AKI and CKD. A full virologic cure is only possible with complete eradication of the viral reservoir in the kidney. Renal disease associated with HIV infection is primarily a glomerular dominant disease, classified into two maincategories:podocytopathies and immune complex-mediated disease. Specific infection screening considerations in HIV positive TX HPV screening post transplantation: Post-TX MAY make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection. Secondary causes should be sought in post-infectious glomerulonephritis. HIV-associated nephropathy incidence peaked in the mid-1990s but has declined due to increased use of combined anti-retroviral treatments.
Pathophysiology: HIV-Associated Nephropathy: HIV-Associated Nephropathy is caused by the expression of HIV-1 genes in the kidney epithelial cells, which is mediated via transfer from leukocytes and phagocytosis of apoptotic CD4+ T cells. Polymorphisms in APOL1 result in an increased riskof HIVAN. HIV-Associated Immune Complex Kidney Disease HIV-associated immune complex kidney disease is caused by co-infection with hepatitis B and C, but the mechanism and relevance of post-antiretroviral therapy is unknown. HIV-Associated Thrombotic Microangiopathy Thrombotic microangiopathy is caused by exposure to circulate viral proteins combined with medications, proinflammatory molecules, and antiphospholipid antibodies. Histopathology HIVAN it is the classic kidney disease that has been associated with HIV infection as a complication of AIDS. Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubulo-reticular inclusion bodies, with diffuse effacement of podocyte foot process and endothelial tubular inclusions may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants. Due to the cART, the incidence of HIVAN is declining. Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESRD.
Patients with HIVAN have: Advanced HIV disease with a CD4 of less than 200 Nephrotic range proteinuria Rapid decline in kidney function HIV-associated nephropathy is characterized by collapsing glomerulopathy and tubulointerstitial disease, HIV-related kidney diseases fall under four pathologic classifications: Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases. Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial, or fungal pathogens Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis. Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis. History and Physical: HIV-associated nephropathy is characterized by a rapid decline in GFR and proteinuria, but other manifestations are uncommon. Evaluation: Screening for HIV nephropathy in HIV positive patients should include serum creatinine and estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline when ART is initiated or changed, and at least twice a year in stable patients infected with HIV. Imaging modalities, such as ultrasonography of the kidneys, may be useful in specific settings, but a kidney biopsy is often the only means of achieving a definitive diagnosis. CART induced nephropathy is more common than HIVAN, presenting with CD4 count <200 cells/mm, viral load >400 copies/mL, rapid decline in renal function, proteinuria >300 mg/24h, hyaline or proteinaceous casts on urinalysis, and large-sized kidneys with intense cortical echogenicity. Diagnosis:
The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
Suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
Kidney biopsy is gold standard for diagnosis of HIVAN.
There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease. Differential Diagnosis: Noncollapsing focal segmental glomerulosclerosis (FSGS) HIV-associated immune complex kidney disease Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection) Amyloidosis Minimal change disease Postinfectious glomerulonephritis Thrombotic microangiopathy Diabetic nephropathy Immunoglobulin A nephropathy Membranous glomerulopathy Differential diagnosis Collapsing glomerulopathy:
FSGS primary (idiopathic) FSGS
Parvovirus B19 infection
SV40 infection
acute CMV infection
Erythrophagocytosis syndrome
Interferon therapy
Pamidronate toxicity
Acute vaso-occlusive injury
Rare familial forms Treatment: HIVAN is associated with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, so 1-Combined antiretroviral therapy is the mainstay of treatment for all patients with HIV infection regardless of CD4 count.
It is important to adjust cART therapy to renal function, and renal replacement therapy remains the mainstay. Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs) are also important, and steroids can be added as an adjunct.
SGLT2 inhibitors Prophylactic therapy: Prophylaxis against PCP and CMV is like regimens used at most centers for HIV negative recipients. Vaccinations prior to transplant: Pneumococcal vaccine given to all patients on the waiting list pre-TX. Hepatitis A and B vaccine, if indicated, should be given before the transplant. Influenza vaccine once yearly. HZV vaccination in high-risk patients (>50 years old). HPV vaccine should be given in selected patients, usually under the age of 45 years. All patients must be up to date with DPT & MMR vaccinations before transplantation. Vaccinations post-transplant: Annual influenza vaccination is recommended. Use of live virus vaccine not recommended (MMR should not be given post-transplant) It is recommended to wait 3 to 6 months after transplant before giving vaccines. If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment. Immunosuppression and antiretroviral therapy challenges Interaction between protease and non-nucleoside reverse transcriptase inhibitors with the CNI and mTOR inhibitors. Variable drug levels between patients and often CNI dosages must be significantly increased or decreased because of these drugs on the cytochrome P450 enzyme. Prognosis: The prognosis in patients with HIVAN is poor, even among those treated with ART. HIVAN consistently do worse than those with other causes of renal disease. Many HIVAN patients will develop end-stage kidney disease (ESKD). Complication: HIVAN can lead to CKD, ESRD, hypertension, and lower extremity edema. Deterrence and Patient Education: HIV-associated nephropathy is an aggressive disease that can lead to end-stage renal disease, so patients should be encouraged to be compliant with antiretroviral medications and follow up with their primary care clinician and nephrologist on a regular basis. Pearls and Other Issues Combined antiretroviral therapy is the mainstay treatment for HIVAN, but other aetiologies are more common due to cART and improved survival. An interprofessional team approach should be used to improve patient outcomes, including frequent renal function testing and biopsy. CD4 count and viral load should be considered for cART initiation. What are the chances of recurrence of HIVAN post-transplantation? HIV-positive patients who underwent a second transplant had a 1.96-fold higher risk of allograft loss and a 3.1-fold increased risk of death. The risk of recurrence of collapsing FSGS is approximately 30% after transplantation. Prognosis is poor for HIVAN recurrence after kidney transplantation. Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence. HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients. Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney. Reference HIV and Kidney Transplantation by Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool -UK
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013;62(2):335-338. doi: 10.1053/j.ajkd.2013.01.010
Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int 92: 461–469, 2017
Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018 May;27(3):144-152. Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kathryn Manning, Peter Chin-Hong, Peter Stock, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies, Transplantation. 2021 July 01; 105(7): 1492–1501. doi:10.1097/TP.000000000000 3485.
Please counsel this patient discussing the pros and cons of transplantation.
PROS:
Long term outcomes are always superior after kidney transplanation than remaining on dialysis
Long term graft and patient survival after kidney transplantation in HIV positive individuals are comparable with non-HIV patients, if all inclusion criteria are met.
Preferably if donor is live related and HIV negative, then results can be very good
Dialysis relayed complications and lifestyle restriction can be prevented with kidney transplantation especially when recipient is youth.
CONS:
Increased risk of graft rejection, development of opportunistic infection
Issues in establishing target theurapeutic levels if immunosupression
Increase in HIV viral load after transplanation
Will you elaborate more on HIVAN?
Renal disease remains one of the major causes of mortality in patients infected with HIV.
HIV can infect and replicate within renal epithelial cells.
Renal disease associated with HIV infection is primarily a glomerular dominant disease that is further classified into two main categories: podocytopathies and immune complex-mediated disease.
The major subtypes of podocytopathy that have been described in the setting of HIV infection are classic HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis
The expression of HIV-1 genes in the kidney epithelial cells is required for the development of HIVAN.
CD209 antigen (DC-SIGN), which mediates HIV infection of dendritic cells, and lymphocyte antigen 75 (DEC-205), which may directly contribute to infection of renal tubular epithelial cells.
HIV-associated nephropathy is defined as a collapsing glomerulopathy and associated tubulointerstitial disease, which may include tubular microcysts and inflammation of the interstitium.
Diffuse effacement of podocyte foot process and endothelial tubular inclusions are mainstays when examined by electron microscopy. Staining for IgM, C3, and C1q in collapsed segments and mesangial areas is common by immunofluorescence.
What are the chances of recurrence of HIVAN post-transplantation?
Yes there are chances of HIVAN re currance, but exact data is lacking and needs more studies.
REF:
Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021;105(7):1492-1501. doi:10.1097/TP.0000000000003485
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
– Please counsel this patient discussing the pros and cons of transplantation.
I will tell him that kidney transplantation is now accepted as “standered of care” for HIV -positive patients with end stage renal disease .,but to be qualified for transpalntation ,he must meet the transplant center s general medical and surgical criteria in addition to HIV -specific metrics ,absence of active infection or malignancy ,undetectable viral load >200 cells/m3 in stable antiretroviral regimens and no history of progressive multifocal leukoencephalopathy ,chronic cryptosporidiosis,central nervous system lymphoma or kaposi sarcoma .
PROS :
HIV positive patients have shown good graft survival and outcome which is even comparable to non HIV patients .
–Decrease waiting time for transplantation with use of HIV positive donors .
– Better lifestyle with less restrictions when get rid of dialysis
-No longer complications related to dialysis.
-Risk of opportunistic infection is not significantly higher when compared to non transplanted HIV patients
CONS :
Increase risk of allograft rejection
HIV patients are also at risk of DGF
Drug interaction is expected especially CNI and HAART drug monitoring is mandatory .
There is an increased chance of post transplant malignancies .
– Will you elaborate more on HIVAN?
– HIVAN is the classic kidney disease of HIV infection and commonest cause of CKD and ESRD in HIV patients ,but fortunately has become less common with widespread use of antiretroviral therapy .
– Patients with African descent has been reported prevalence of HIVAN to be 3% to 12%
Risk factors of HIVAN : Are low CD4 cell count, high HIV viral load, and family history of renal disease.
– Polymorphisms in APOL1 result in an increased risk of HIVAN
Clinical presentation :
–The classical presentation of HIVAN is heavy proteinuria and a rapid decline in kidney function .
Diagnosis :
– Biopsy is the gold standard for diagnosis.
– The classical histological form is collapsing FSGSaccompanied by microcystic tubular dilatation and interstitial inflammation other forms are immunocomplex associated nephropathy and thrombotic microangiopathy
– Proteinuria, urinalysis typically bland; nephritic profile may suggests alternative diagnosis .
-Renal US : will show normal to large size kidneys with increased echogenicity .
Differential diagnosis :
-HIV-associated immune complex kidney disease
– Membranous glomerulopathy
– Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)
– Minimal change disease
– Diabetic nephropathy
– Immunoglobulin A nephropathy
– Thrombotic microangiopathy
Treatment :
– ART is very effective in reverse or stabilizing renal dysfunction, preventing progression, and improving long-term renal function and survival outcomes.
– Control the BP and blood sugar .
– Corticosteroids as adjunct to ART +/- ACEi/ARB may give rapid response .
– Revision of all medications looking for the need of renal dose adjustments ,or if there is use of over counter medications and NSAID.
– It has increasingly been recognized that APOL1 gene risk alleles play a pivotal role in the development and progression of HIVAN which may be targeted for future therapy.
– What are the chances of recurrence of HIVAN post-transplantation?
Recent studies of HIVAN in post kidney transplant patients showed favorable results, but there is a risk of recurrence especially with HIV positive donors and when the living donor has a high-risk variant of the APOL1 gene which may lead to rapid decline of kidney function in both donor and recipient .
I agree with the figures that you have quoted for HPVAN recurrence rate, that are realistic.
Too much use of bullet points even before the headings is not a good idea. You have used bullet points with hyphen and at places where there is no word,
Please counsel this patient discussing the pros and cons of transplantation.
Proper patient counselling is the cornerstone of the initial steps of improving patient centered quality of life.
Starting by the pros; renal transplantation is by far the best therapeutic option for ESRD ,improving lifestyle, avoiding complications associated by dialytic support ( risk of cardiovascular complications, bone mineral disease affection, risk of repeated blood transfusion and other encountered adverse effects), achieving dependent lifestyle compared to haemodialysis. Renal transplantation has been feasible after the advances of c ART therapy and improved further success results.
While the cons that are really challenging are the following ; the increased probability of acute rejection episodes , marked susceptibility to opportunistic infections as CMV ,PCP and others which may be life threatening requiring long-term prophylactic protocols. Although there have been advances in c ART therapy, yet there are expected drug interactions among immunosuppressive medications and c ART therapy may pose the patients to hazardous risks of viral replication or the higher incidence of rejection.
Will you elaborate more on HIVAN?
HIVAN occurs mainly by the expression of HIV-1 genes within the renal epithelial cells. However the culprit mechanism is still unknown how the HIV infects renal epithelial cells. Some studies revealed that macrophages and lymphocytes seem to be vectors for renal epithelial cell transmission of HIV. The CD209 antigen (DC-SIGN) is one of the antigens studied that can directly contribute to infection of renal tubular cells mediating HIV infection of dendritic cells, and lymphocyte antigen 75 (DEC-205). Polymorphisms in APOL1 may result in an increased incidence of HIVAN. Phagocytosis of apoptotic CD4+ T cells are also suggested as one of the possible mechanisms by which HIV enters renal epithelial cells. The HIV proteins Vpr and Tat circulate in plasma as well as proteoglycans, and lipid get access to podocytes.
Screening for HIV nephropathy relies on serum creatinine, estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline after c ART therapy is administered or changed for at least twice a year in stable patients. Renal biopsy remains the definitive means for diagnosis. Histologically, it resembles collapsing FSGS however the presence of tubuloreticular inclusions within the endothelial cells distinguishes them by EM.
Treatment essentially by c ART therapy in addition to ACEI to delay progression to ESRD.
What are the chances of recurrence of HIVAN post-transplantation?
Recurrence rate post renal transplantation is assumed to be high resembling FSGS about 30 %. This can be detected early on histological level in protocol biopsies without even clinical manifestations. Unfortunately according to the scares data recurrence of HIVAN may not be prevented by the use of cART therapy.
PLoS One. 2015; 10(6): e0129702.
Published online 2015 Jun 10. doi: 10.1371/journal.pone.0129702
PMCID: PMC4463848
PMID: 26061701
Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy
According to this study, among 11 patients biopsy proven HIVAN, one patient had recurrence which was biopsy proven although undetectable HIV RNA viral levels. It was suggested then that HIV can be detected in 68% of renal allografts specifically in podocytes and tubular cells. It also concluded that, the 1- and 3-year rejection rates were 18% and 27%.
Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplantation is the standard of care treatment for end stage renal disease, notwithstanding the HIV status of the recipient (1).
Pros of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
cART availability has made it possible to offer transplantation as a viable treatment option for HIV-positive patients, provided they fulfill certain criteria (2).
Superior survival as compared to remaining on dialysis, especially with live kidney donors (1,3).
Use of HIV-positive donors can reduce the waiting time for HIV-positive recipients drastically (4).
Opportunistic infections encountered post-transplant in HIV-positive patients are not significantly higher than HIV-negative recipients (4).
Cons of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
Significantly increased rates of rejection (2-3 times) and delayed graft function than in the general population (5).
Increased incidence of bacterial infections, especially those receiving antithymocyte globulin (ATG) or with HCV co-infection (5).
Increased drug-drug interactions between cART and immunosuppressive agents (4).
Decreased patient and allograft survival seen in older recipients, those on pre-transplant dialysis, with diabetes mellitus, and those with delayed graft function and acute rejection (1).
Use of ATG has been shown to be associated with decreased patient and graft survival but later studies have shown decreased rejection rates (1).
Malignancies associated with human papilloma virus have been seen more commonly (1).
Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN) is the first kidney disease diagnosed in HIV-infected patients, having nephrotic syndrome (having collapsing form of focal segmental glomerulosclerosis, FSGS), rapid progression to end stage renal disease (ESRD), and irreversible renal failure (6).
Risk factors for HIVAN: HIVAN risk is 50 times more in African-Americans than in whites, with increased risk with presence of 2 APOL1 risk alleles (6). Other risk factors include CD$ count <200, high viral load (>400 copies/ml), proteinuria >3g per day, and eGFR<90 ml/min with elevated serum creatinine from baseline (7).
Patients clinically present with moderate to heavy proteinuria with bland urinary sediments. Edema and hypertension are not typically seen in HIVAN. Patients will present with progressively decreasing renal function, and will have high viral load and low CD4 counts signifying advanced HIV infection. Ultrasound of the kidneys reveals enlarged, echogenic kidneys, requiring a kidney biopsy to differentiate it from other causes (like diabetic nephropathy, amyloidosis, classic FSGS, membranous nephropathy, and membranoproliferative glomerulonephritis). The histopathological changes seen with HIVAN include collapsing FSGS, interstitial nephritis, visceral epithelial cell proliferation, endothelial tubuloreticular inclusions, and tubular microcystic dilatation (6).
Management of HIVAN involves initiation of cART (regardless of CD4 count), ACE inhibitors or ARBs (if no contraindication), and avoiding nephrotoxic agents. Steroids have been used to reduce tubulointerstitial inflammation, in patients with rapidly progressing renal dysfunction despite optimal RAAS inhibition and cART use. In case of ESRD development, renal replacement therapy in form of dialysis and transplant is available. Renal transplant should be offered if the patient fulfils certain criteria like CD4 count >200 and undetectable viral load (2).
What are the chances of recurrence of HIVAN post-transplantation?
The risk of HIVAN recurrence post-transplant, especially if the donor is HIV-positive has been seen (6). There is no correlation between the recurrence of HIVAN and viral loads (4). The exact location of viral reservoir in the transplant kidney with rapid worsening of renal function seen if the virus is identified in the podocyte (rather than in the tubular cell) of the transplanted kidney (8). HIVAN recurrence has not been found to be clinically relevant in a US multicenter trial (6). Since HIVAN is a secondary form of FSGS (due to HIV infection), if HIV infection is managed well with cART, the chances of recurrence are low. Hence it is important to put more emphasis on cART, and especially immunosuppressive-drug interactions in the transplant recipient.
References:
Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.
Lucas A, Wyatt CM. HIV at 40: kidney disease in HIV treatment, prevention, and cure. Kidney Int. 2022 Oct;102(4):740-749. doi: 10.1016/j.kint.2022.06.021. Epub 2022 Jul 16. PMID: 35850290; PMCID: PMC9509437.
Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11. doi: 10.1159/000526868. PMID: 36816427; PMCID: PMC9936764.
Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA, Atta MG. HIV-associated nephropathy: links, risks and management. HIV AIDS (Auckl). 2018 May 25;10:73-81. doi: 10.2147/HIV.S141978. PMID: 29872351; PMCID: PMC5975615.
Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, Viard JP, Anglicheau D, Bienaimé F, Muorah M, Galmiche L, Gribouval O, Noël LH, Satie AP, Martinez F, Sberro-Soussan R, Scemla A, Gubler MC, Friedlander G, Antignac C, Timsit MO, Onetti Muda A, Terzi F, Rouzioux C, Legendre C. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014 Feb;25(2):407-19. doi: 10.1681/ASN.2013050564. Epub 2013 Dec 5. PMID: 24309185; PMCID: PMC3904571.
Please counsel this patient discussing the pros and cons of transplantation.
kidney transplantation is a valid therapeutic option for HIV-positive patients with end-stage kidney disease(1).
Pros of transplantation:
1. Survival rates following kidney transplantation are higher in comparison with patients remaining on dialysis.
2. Patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation.
3. KT in HIV patient is cost-effective when compared to those remaining on dialysis.
4. Improved quality of life of PWH.
5. Better long-term prognosis of an HIV-positive patient.
Cons of transplantation:
1. Some studies report disturbingly high acute rejection rates.
2. Infectious complications following solid-organ transplantation are common and may be life- or graft-threatening.
3. Reactivation following immune suppression may occur with previously indolent infections.
4. Some of the commonly used antiretrovirals, have been associated with kidney injury and kidney disease progression.
5. EBV sero-negative recipients of an organ from an EBV seropositive transplant have a seven-fold increased risk of post-transplant lymphoproliferative disorder (PTLD).
6. High prevalence of HBV and HCV infection.
7. High rates of liver disease progression (cirrhosis, hepatocellular carcinoma) have been reported in untreated HBV co-infected patients who underwent kidney transplantation.
8. Increase the incidence of human papilloma virus (HPV)-associated cancer.
9. Increase the incidence of KS.
10.Drug-Drug interaction: Protease-inhibitors, dramatically increase CNI and mTORi exposure, thus requiring significant dose reductions( e.g. 90% CsA and 99% tacrolimus dose reduction). NNRTIs are enzyme-inducers that reduce CNI and mTOR-inhibitor drug concentrations. No significant drug interactions have been noted for CNIs or mTOR-inhibitors when co- administered with the integrase-inhibitor.
Will you elaborate more on HIVAN?
1. HIV-associated Nephropathy (HIVAN) is most prevalent in patients who receive antiretroviral therapy (ART) late after initial diagnosis, and is a major cause for CKD in developing countries(2).HIVAN almost exclusively affects persons of African descent, who account for approximately 90% of HIVAN-related cases of ESRD(3).
2. HIVAN is manifested by collapsing glomerulopathy. Kidneys are often enlarged in HIVAN patients.
3. Patients with HIVAN manifest nephrotic syndrome, often have increased serum creatinine at presentation, and show rapid progression, with about half reaching ESRD after 3 years.
4. The prevalence of HIVAN among HIV-infected individuals has decreased dramatically since the advent of combination antiretroviral therapy (cART) as standard of care for these patients.
5. HIVAN/HISTOPATHOLOGY(4):
a) Light microscopy: Segmental or global glomerular tuft collapse with overlying visceral epithelial hyperplasia and hypertrophy is seen. Hypertrophied visceral epithelial cells have frequent protein droplets. There is accompanying microcystic tubular dilatation and active tubulointerstitial nephritis with a predominantly lymphocytic infiltrate, often with tubulitis and edema.
b) Immunofluorescence microscopy: No or limited immune deposits (nonspecific IgM and C3 staining in collapsed segments) are identified. Protein droplets in visceral epithelial cells may stain for immunoglobulins and albumin.
c) Electron microscopy: Glomerular basement membranes are wrinkled and collapsed. Overlying visceral epithelial cells show hypertrophy and hyperplasia, with frequent vacuoles and protein droplets. There is extensive foot process effacement and no or limited mesangial deposits. Tubuloreticular aggregates are present in endothelial cells, in contrast to idiopathic collapsing glomerulopathy, in which such aggregates are typically absent. Tubuloreticular aggregates may be rare or even absent in patients with low viral loads who are receiving cART.
6. Key Diagnostic Features
· A clinical history of HIV infection and the presence of tubule-reticular aggregates indicate HIVAN as the etiology of the collapsing lesions.
· Extensive foot process effacement.
· Tubuloreticular aggregates in endothelial cells
· Absence of immune complex deposits
· Collapsing glomerulopathy, with collapse of tuft, segmental or global, with overlying visceral epithelial cell proliferation
· Microcystic tubular dilatation with active tubulointerstitial inflammation.
7. HIVAN/Differential Diagnosis
· Crescentic GN.
· Collapsing glomerulopathy can be related to other infections (eg, parvovirus), drugs (eg, bisphosphonates and calcineurin inhibitors), severe vascular disease (eg, thrombotic microangiopathy and cocaine use), and autoimmune disease (eg, systemic lupus erythematosus), or may be idiopathic. A clinical history of HIV infection and the presence of tubuloreticular aggregates indicate HIVAN as the etiology of the collapsing lesions.
What are the chances of recurrence of HIVAN post-transplantation?
1. The largest prospective study to date included 150 HIV-positive patients and reported patient and graft survival rates of 88% and 74% at three years, which was somewhat below that of the general US kidney transplant population(3).
2. In 2005, Kumar et al reported a study of 40 HIV-positive patients. They observed that the 1-and 2-year patient survival rates were 85% and 82%, respectively. The corresponding graft survival rates were 75% and 71%, with a 22% acute rejection rate. The HIV viral load remained undetectable, and the CD4 T cell counts were > 400 cells/mm3. No opportunistic infections or progression to AIDS were observed in these patients at 2 years. Interestingly, the authors noticed that 3 of 40 patients had HIVAN recurrence on the allografted kidney. One of these patients was asymptomatic, and the HIVAN diagnosis was made on a protocol biopsy(5). References
1. Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
2. Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clin Nephrol. 2015; 837 Suppl 132-38
3. Medscape;Drugs & Diseases; Nephrology: HIV-Associated Nephropathy and Other HIV-Related Renal Disorders Updated: Mar 16, 2023 Author: Moro O Salifu, MD, MPH, MBA, MACP; Chief Editor: Vecihi Batuman, MD, FASN
4. ATLAS OF RENAL PATHOLOGY II| VOLUME 68, ISSUE 2, E13-E14, AUGUST 2016 AJKD Atlas of Renal Pathology: HIV-Associated Nephropathy (HIVAN) Agnes B. Fogo, MD Mark A. Lusco, MD Behzad Najafian, MD Charles E. Alpers, MD DOI:https://doi.org/10.1053/j.ajkd.2016.06.002
5. Kumar MS, Sierka DR, Damask AM, et al. Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients. Kidney Int. 2005;67:1622–1629.
Thanks, Safi Looks that the recurrence of HIVAN was very small in the study you mentioned. Only 3 out of 40. What are the factors associated with the recurrence of HIVAN?
Psychological impact as a family member involved in related donation.
Time and cost expenses.
Major surgery.
Risk of rejection, (lifelong anti-rejection therapy).
Opportunistic infection.
Frequent lab tests and doctor visits.
HIVAN
Is the classical form of glomerular disease in HIV-AIDS, collapsing form of FSGS.
It reduce in incidence with improving ART.
Also it can be occurred in mild form of HIV infection.
Recuurence after Kidney transplantation
HIVAN recurrence is at concern in HIV+ recipients and donors.
The incidence is variable between study reports and may not related to viral load.
General concern should be considered, (measured to prevent rejection, reduce opportunistic infection, and ART and maintain low level of viral load.
Regular check up kidney function and proteinuria.
References
1.Uptodate.com/contents/hiv-associated-nephropathy-hivan/abstract/1
Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clin Nephrol. 2015; 837 Suppl 132–3
2. Cohen SD, Kopp JB, Kimmel PL. Kidney diseases associated with human immunodeficiency virus infection. N Engl J Med. 2017; 377:2363–2374
The recurrence of HIVAN after kidney transplantation is registered, the incidence is low but variables with different studies. Recurrence of the disease as a classical HIVAN or another form of disease associated with HIV infection, make a burden of kidney disease on those populations. There are many forms of kidney diseases (more noticed in ART-treated patients) but the most common form
Immune complex associated GN.
Lupus-like nephritis is a form of immune complex in HIV infected patients with a histological feature of Lupus nephritis, with absence of serological markers.
A study done in South Africa among 51 recipients with HIV with serial protocol biopsies with indication, show that 12 recipients had some form of HIVAN.
HIVAN occurs late after transplantation associated with the lower clinical sequel.
Most of HIVAN not associated with viral load.
The graft and patient survival is to some extent similar to a non-HIV recipients.
Transplanted HIV-infection patient has a better survival than HIV-infected patients being on dialysis.
⭐ Renal transplantation still has better survival than continuation on dialysis for HIV patients
_pros: decrease cardiovascular mortality related to dialysis
Cons.: Need for close follow up of graft function, Drug drug interaction between ART and CNI, HIV control, increased risk of opportunistic infections as CMV and PJP, higher risk of DGF and AR than HIV naive, higher risk of malignancy.
👉 👉 HIVAN is common in African population, especially with APOL 1 gene mutation.
_ can be in many forms either:.
1_ glomerular as FSGS (collapsing variant).
2_ tubulointerstitial form with ATN and tubulointerstitial nephritis.
3_ vascular form as TMA.
4_ Diabetic nephropathy or astherosclrotic vascular changes
⭐ ⭐ ⭐ The risk of recurrence of HIVAN is depending on controlling the underlying disease as HIV infection (depends on adherence to ART , presence of resistance strains, control of HIV disease as PCR and CD4 count, use of appropriate IS therapy with caution regarding drug interaction between CNI and ART….better to use integrase inhibitors not protease inhibitors )
Thanks dear professor .
_Previous studies included that the recurrence of HIVAN is low (as FSGS is secondary to HIV infection) which is prevented by controlling HIV infection by ART.
_However, many risk factors has been associated with recurrent HIVAN as Postive HIV donor (with viral reservoir in the allograft, lower CD4 cell count, inappropriate ART adherence or drug interaction with CNI).
HIVAN is frequent in patients who are incompliant or do not receive cART therapy due to the replication of HIV in renal cells. The patient is young, and renal transplantation is beneficial after fulfilling the eligibility criteria. The patient should know that compliance with treatment (cART) is of almost importance. He should be informed about the complexity, drug-drug interaction, and risks of viral infections (like CMV & Polyomavirus). We need to make sure about the situation of immunity and CD4+ cell count (>200).
HIVAN can relapse after transplantation. In patients with HIVAN, antiretroviral treatments is initiated regardless of CD4+ cell count.
Acute rejection is also reported to be higher in HIVAN patients compared to normal population (Waheed et al.)
———- Rivera, F. B., Ansay, M. F. M., Golbin, J. M., Alfonso, P. G. I., Mangubat, G. F. E., Menghrajani, R. H. S., … & Kazory, A. (2022). HIV-associated Nephropathy in 2022. Glomerular Diseases.
Waheed S, Sakr A, Chheda ND, Lucas GM, Estrella M, Fine DM, Atta MG. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015 Jun 10;10(6):e0129702. doi: 10.1371/journal.pone.0129702. PMID: 26061701; PMCID: PMC4463848.
Counsel this patient discussing the pros and cons of transplantation. Though kidney transplantation is the best modalities of RRT but here counselling is necessary including pros and cons. · About living versus deceased donor. · Screening for all opportunistic and community acquired infections with proper immunization. · Screening for malignancies. · Regarding Immunosuppression protocol for induction and maintenance along with drug interaction between HAART and CNI. · Prophylaxis for opportunistic infection.
Pros: · Kidney transplantation is the best form of RRT. · Because availability of c-ART, we can Accept HIV + deceased Donor. · With current cART, we can expect a near-normal life expectancy. · In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation. · Better survival than being on waiting list on dialysis.
Cons: · The risk of acute rejection is high (>50%) · Risk of nephrotoxicity with anti-retrovirals · Antiretrovirals with possible drug-drug interactions with immunosuppressants. · Increase Risk of post-transplant infections and malignancy
HIVAN: · HIV-associated nephropathy (HIVAN) is a collapsing form of focal segmental glomerulosclerosis (FSGS) secondary to HIV. · Involves direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host. There is strong associations of HIV with Africans and APOL1 gene polymorphisms. · Presents with massive proteinuria and a rapid deterioration of renal function. · Suspicion is high when CD4 cell count <200, HIV viremia and Nephrotic Syndrome. · Kidney biopsy is gold standard for diagnosis of HIVAN. · For patients with HIVAN, ART should be initiated as soon as possible if not already taking. Medication adherence should be assured. · Poor prognosis. Chances of recurrence of HIVAN post-transplantation: There are chances of recurrence in the graft post-transplantation, particularly if the donor is HIV positive
References: 1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015. 2. Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916. 3. DAqati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998; 18:406. 4. Winston JA, Bruggeman LA, Ross MD, et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001; 344:1979.
Please counsel this patient discussing the pros and cons of transplantation.
Prerequisite for recipient are
CD4 of more than 200
HIV viral load of less than 50 RNA copies /ml.
Adherent to ART medications.
No history of active infection
Pros of transplanation are
Better quality of life
Better survival than being on waiting list on HD/PD
Good graft survival
Aproximate graft survival during the 1-year and 3-year mark was 90% and 74%, respectively)
Cons of transplantation are
More chances of rejection
More chance of DGF
More post-transplant infections
Need of more post-transplant prophylaxis
Have Drug interactions between HAART and immunosuppression needing drug monitoring
More chances of post-transplant malignancies
Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN) usually begins with large amounts of protein in the urine and progresses rapidly to total kidney failure. HIVAN is very uncommon in people whose HIV is effectively controlled by antiretroviral (ARV) drugs. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load, and low CD4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV-positive patients. However, has been reported in Caucasian, there are few cases report. Renal parenchymal injury is characterized by epithelial cell proliferation, de differentiation and apoptosis along the entire nephron.
HIV-related kidney diseases fall under four pathologic classifications.
Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial or fungal pathogens Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis.
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis
Clinical manifestations
Nephrotic-range proteinuria
Rapid decline in kidney function
Hematuria
Hypertension
Edema
Management
Combined antiretroviral therapy.
ACE inhibitor or ARB
Steroid as an Adjunct
What are the chances of recurrence of HIVAN post-transplantation?
In the South African group of 51 transplants, 12 patients were reported to have some HIVAN related changes on biopsy, but only 2 patients lost their grafts as a result. These patients also had episodes of rejection in the first 3 years after transplantation.
References
1) Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients [published correction appears in N Engl J Med. 2011 Mar 17;364(11):1082]. N Engl J Med. 2010;363(21):2004-2014. doi:10.1056/NEJMoa1001197
2) Swanepoel CR, Atta MG, D’Agati VD, Estrella MM, Fogo AB, Naicker S, et al. Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018 Mar. 93 (3):545-559.
3) Yalavarthy R, Smith ML, Edelstein CL. HIV-associated nephropathy in Caucasians: case report and review of literature. Int J STD AIDS. 2008 Nov;19(11):789-90. doi: 10.1258/ijsa.2008.008091. PMID: 18931278.
4) Waheed S, Sakr A, Chheda ND, Lucas GM, Estrella M, Fine DM, Atta MG. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015 Jun 10;10(6):e0129702. doi: 10.1371/journal.pone.0129702. PMID: 26061701; PMCID: PMC4463848.
5) Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplantation is the best form of treatment for ESRD. It is better outcomes if proper medical , surgical and psychological workup is done. Kidney transplantation in HIV positive patients was not a common entity but this has changed in recent years. Transplantation in HIV patients has better outcomes than dialysis. Graft outcomes are better with new HAART medications. I will counsel the patient about renal transplantation by telling about pros and cons of transplant.
Benefits of transplant
Better quality of life
Less deaths due to CVD
Better outcomes
Cost effective
Hormonal and metabolic kidney functions restored
Disadvantages of Kidney transplant
Higher rejection rates
High risk of drug interactions and nephrotoxicity
Higher malignancy rates
Will you elaborate more on HIVAN?
It is commonest cause of ESRD in HIV positive patients and can lead to severe form of CKD. Renal disease remains one of the major causes of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from acute kidney injury (AKI) and chronic kidney disease (CKD). In Black population it is associated with APOL 1 Gene mutation. Lesions resulting directly from intrarenal HIV gene expression and injuries secondary to co morbidities, drug-induced nephrotoxicity, and immune dysregulation, are some of the leading factors. With HAART the incidence has decreased .
Histology
Collapsing glomerulopathy and associated tubulointerstitial disease, which may include tubular microcysts and inflammation of the interstitium. Diffuse effacement of podocyte foot process and endothelial tubular inclusions are mainstays.
Differential diagnosis
HIV-associated immune complex kidney disease
Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)
Amyloidosis
Minimal change disease
Postinfectious glomerulonephritis
Thrombotic microangiopathy
Diabetic nephropathy
Immunoglobulin A nephropathy
Membranous glomerulopathy
Diagnosis
Serum creatinine and estimated glomerular filtration rate (GFR)
Urinalysis or a quantitative measure of proteinuria
Ultrasonography of the kidneys
Kidney biopsy
Management?
Combined antiretroviral therapy continues to be the mainstay of treatment
Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
In refractory renal impairment after cART and RAAS blockade treatment, steroids can be added as an adjunct
In ESRD, renal replacement therapy remains the mainstay of management, and renal transplantation can be considered
What are the chances of recurrence of HIVAN post-transplantation
I could find exact data or evidence on this. After HIVAN recurrence prognosis is poor
Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
· Please counsel this patient discussing the pros and cons of transplantation. Renal transplantation is the treatment option for fit patient with life expectancy is >5 years. Pros: 1-Better survival than being on waiting list on dialysis. 2-HIV infection remained well controlled by cART. 3-Improving QOL. 4-Decreasing cost of RRT. Cons: 1-Increased risk of acute rejection. 2-Reduction of CD4 count sometimes with ATG use. 3-Incresaed risk of infections. 4-Drug interaction between Immunosuppression and cART. 5-Co-infection with HCV is associated with more serious infection. 6-Higher rates of DGF. · Will you elaborate more on HIVAN? HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS. The commonest cause of CRF is HIV-associated nephritis (HIVAN). Exclusive in BLACK RACE, the most common form is collapsing FSGN, and is considered the third leading cause of CKD in Blacks. The pathogenesis of HIVAN is hypothesized to involve several factors: 1-Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells 2-Host factors, including genetic susceptibility. In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN. Presented by : A-Sever advanced HIV disease. B-Nephrotic-range proteinuria. C-Rapid decline in kidney function. HAART (Highly Active Anti-retrovirus Therapy),also called cART (Combination Anti-Retrovirus Therapy), can be given as single agent (ART) has improved the prognosis of HIV patients. Treatments that have been examined for patients with HIVAN include 1-Antiretroviral therapy (ART). 2-Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). 3-Glucocorticoids. But still no randomized control studies shown the definitive plan of management. · What are the chances of recurrence of HIVAN post-transplantation? No enough data clarifying this point , but one study shown that kidney transplant appears effective in patients with HIVAN despite elevated rates of DGF and no recurrence detected post kidney transplant and further studies are needed to evaluate this issue(2). References: 1- Malat GE, Boyle SM, Jindal RM, et al. Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience. Am J Kidney Dis. 2019;73(1):112-118. doi:10.1053/j.ajkd.2018.02.352. 2- Waheed S, Sakr A, Chheda ND, et al. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015;10(6):e0129702. Published 2015 Jun 10. doi:10.1371/journal.pone.0129702
· HIV per se is not a contraindication for kidney transplantation
· HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma
pros
· outcomes for patient with HIV are favorable, with transplantation providing a clear survival benefit over renal replacement therapy
· availability of cART has made it feasible to offer kidney transplantation to HIV-positive patients with better survival and better graft out come
· Because all patients had viral suppression and CD4þ cell counts at least 200 cells/ml prior to transplant and combination ART and post- transplant anti-infective prophylaxis was employed, HIV control was excellent, and few opportunistic infections were encountered.
Cons
· patient with HIV experienced high rates of delayed allograft function (this did not appear to be predictive of graft failure. Finally,
· HIV recipients experienced allograft rejection rates two to three times higher than observed in the general kidneytransplant population
· Bacterial infec tions were observed with increased frequency in HIV recipients who were treated with antithymocyte globulin (ATG) or coinfected with HCV.
· Classic HIVAN, as originally described in the pre-ART era continues to occur among ART-naïve or non-adherent patients, usually of African descent, irrespective of the mode of HIV transmission.
· Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV positive patients. · Pathologically HIVAN is defined by a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy.2 Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features. · In patients with classic HIVAN, the following features are usually present: ●Advanced HIV disease – Patients with HIVAN typically have a CD4 count less than 200 cells/microL. ●Nephrotic-range proteinuria ●Rapid decline in kidney function – Other manifestations, such as hematuria, hypertension, and edema, may also be present diagnosis Kidney biopsy is currently the only way to establish a definitive diagnosis of HIVAN Differential diagnosis ●Noncollapsing focal segmental glomerulosclerosis (FSGS) – ●Immune complex-mediated glomerulonephritis, including immunoglobulin A (IgA) nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, and a “lupus-like” proliferative glomerulonephritis. ●Glomerulonephritis due to coinfection with hepatitis C or hepatitis B virus..) ●Diabetic kidney disease, amyloidosis, or other noninfectious glomerulopathies Treatment · Antiretroviral therapy for all patients — All patients with HIV infection should receive ART, regardless of CD4 count. · Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs ) · SGLT2 inhibitors
HIVAN recurrence is a concern HIV positive transplant programs. In the South African group features of HIVAN presented many years after the transplant and had a slow progression having no clinical impact in most cases. In the South African group of 51 transplants, 12 patients were reported to have some HIVAN related changes on biopsy, but only 2 patients lost their grafts as a result. These patients also had episodes of rejection in the first 3 years after transplantation. All patients who had HIVAN recurrence had undetectable viral loads all through the study.
In the USA multicentre trial reporting on more than 150 HIV positive patients, HIVAN was not a clinical issue and was observed in 2/150 positive patients
All patients with HIV and ESKD should be offered transplant if there CD4 count is more than 200 cells/microliter for at least 3 months and the viral load is undetectable for the same period of time and the patient has demonstrated compliance and has no active infection and/or malignancy The pros of transplantation include:
Transplantation provides a clear survival benefit over dialysis even in patients with HIV
In a study by Stock et al, the 1 and 3 year kidney graft survival and patient survival was 90.4 and 73.7% and 94.6 and 88.2% respectively
The risks of OIs were fewer and the HIV control was excellent in the study by Stock et al. This was because the patients selected had a CD4 count of more than 200 cells/microliter and continued with their cART and were on prophylaxis
The cons include:
Increased frequency of bacterial complications especially those treated with ATG
Increased risk of DGF
The rates of acute rejection is 2-3 times than in the non-HIV transplanted population possibly due to inadequate immunosuppression and the chronic inflammatory state in the HIV patient
HIVAN:
It is the classic kidney disease that has been associated with HIV infection as a complication of AIDS. Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubuloreticular inclusion bodies may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants. Due to the cART, the incidence of HIVAN is declining. Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESKD.
Patients with HIVAN have:
Advanced HIV disease with a CD4 of less than 200
Nephrotic range proteinuria
Rapid decline in kidney function
The treatment of HIVAN includes:
HAART
RAAS blockade
SGLT2 Inhibitors can be tried for their anti-proteinuria effect
Risk of Recurrence:
The risk of recurrence of collapsing FSGS is approximately 30% after transplantation
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Thank you Professor Dawlat
The use of SGLT2 inhibitors for non diabetic proteinuria is extrapolated from the post hoc analysis of the DAPA CKD trial which showed a positive benefit in patients with Glomerulonephritis especially IgA nephropathy and FSGS
The EMPA Kidney trial also showed benefit in non diabetic patients with CKD and Glomerulonephritis
The SGLT2 inhibitors are used as an add on if the RAAS blockade is not controlling the proteinuria in IgA nephropathy and FSGS
–Please counsel this patient discussing the pros and cons of transplantation. Patient counselling
Recipients have to have CD4 count >200 cells/µL, an HIV viral load <50 HIV-1 RNA copies/mL, demonstrate adherence to HAART, and free of AIDS-defining illnesses.
HIV-positive transplant candidates should have the standard consent as other recipients
the recipient is encouraged to inform their diagnosis of HIV to their donor Pros
-Kidney transplantation in HIV-positive recipients is associated with marvellous 1-year and 3-year recipient and allograft survival rates, intermediate to those observed in the overall US kidney transplant population and in a higher risk subgroup of recipients ≥65 years also suggest good 5- and 10-year outcomes, with an improvement in survival compared with patients who remain on the waiting list.
-The adjusted relative mortality risk at five years was 79% lower among transplant recipients compared to remaining on dialysis
-response to antiviral therapy have favourable results Cons
-More liable to severe infection specially after immunosuppression with high risk of reactivation
-Insufficient anti-viral treatment to completely suppress viral replication can lead to
emergence of drug-resistant viral escape mutants.
– HIVAN recurrence is a concern in some HIV positive transplants
-Drug -drug interaction between antiviral agents and immunosuppressives
– more liabile for rejection and delayed graft function
-Will you elaborate more on HIVAN?
HIVAN ,is primarily occurring in -naïve or non-adherent patients before ART .
Also common in patients who receive antiretroviral therapy (ART) late after initial diagnosis resulting in progression to organ failure
It’s associated with Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count.
Diagnosed by a nephrotic range proteinuria, and increased renal echogenicity on ultrasound and a kidney biopsy.
Pathologically presented by a collapsing glomerulopathy and tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation and endothelial tubuloreticular inclusions by electron microscopy.
It’s classic features are Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions .
HIVAN recurrence can occur in some HIV cases.
Treated by antiretroviral therapy ,some studies used ACEI and steroids
-What are the chances of recurrence of HIVAN post-transplantation?
HIVAN recurrence can occur in some cases and need further studies as there is no sufficient data . The exact location of the viral reservoir in the transplanted kidney is crucial . A study demonstrated a rapid deterioration in graft function after the diagnosis of HIVAN if the virus is identified in the podocyte not in the tubular cell of the transplanted kidney
Reference
-Salifou M O etal . HIV-Associated Nephropathy and Other HIV-Related Renal Disorders ,Medscape 2022
– Locke JE, Gustafson S, Mehta S, et al. Survival Benefit of Kidney Transplantation in HIV-infected Patients. Ann Surg. 2017;265(3):604-608.
– Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021;105(7):1492-1501.
– Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014;25(2):407-419.
Please counsel this patient discussing the pros and cons of transplantation.
Pros
o Kidney transplantation is better than dialysis
o The access is the same to living donor kidney transplantation as non-infected patients
o HIV per se is not a contraindication for kidney transplantation and HIV-positive patients are wait-listed only if in specific cases including concordance with treatment
o With current cART, we can expect a near-normal life expectancy
o In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation
o Careful immuno-virological and antiretroviral status review with serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus, Toxoplasma gondii, latent Mycobacterium tuberculosis infection and viral hepatitis
Cons
o The risk of acute rejection is high (>50%)
o Possible nephrotoxicity with retrovirals
o Antiretrovirals with possible drug-drug interactions with immunosuppressants
o Lifelong prophylaxis against Pneumocystis pneumonia and other prophylaxis therapy
o Drug-resistance after transplantation
o Patients with HIV infection are unsuitable to be living kidney donors
o Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with specific criteria
Will you elaborate more on HIVAN?
It is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK
o Black are at increased risk (Exclusive in BLACK RACE): 10-13% of African-Americans carry two APOL1 risk alleles, associated with a 7-10 fold increased risk of kidney disease including HIVAN
o Typically young (mean age 36 years)
o With severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median eGFR] 21 mL/min/1.73m2) at diagnosis
o Majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
Pathophysiology:
Characterized by a collapsing glomerulopathy with active tubulointerstitial inflammation. The collapse of glomerular basement membranes is usually observed, along with hypertrophy and hyperplasia of the overlying glomerular epithelial cells, as well as active tubulointerstitial disease manifested by microcytic tubular dilatation, interstitial inflammation and tubular injury
Presentation: Rapid rise in serum creatinine and proteinuria
Differential diagnosis Collapsing glomerulopathy:
1. FSGS primary (idiopathic) FSGS
2. parvovirus B19 infection
3. SV40 infection
4. acute CMV infection
5. erythrophagocytosis syndrome
6. interferon therapy
7. pamidronate toxicity
8. acute vaso-occlusive injury
9. rare familial forms
10. glomerular injury in the renal allograft associated with microvascular disease
Recent studies on renal transplantation in patients with HIVAN have shown favorable results. Graft survival during the 1-year and 3-year mark was 90% and 74%, respectively. Graft rejection is also a major concern in this population, given the baseline immune dysregulation and the drug interactions between cART and calcineurin inhibitors
What are the chances of recurrence of HIVAN post-transplantation?
There is a risk of HIVAN recurrence in the graft posttransplantation, particularly in cases wherein the donor is HIV positive
References
1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015.
2. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
3. Sawinski, Deirdre. Kidney Transplantation in Patients with HIV. Kidney360 1(7):p 705-711, July 2020. | DOI: 10.34067/KID.0002112020
4. Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS Rep. 2019 Jun;16(3):191-203. doi: 10.1007/s11904-019-00440-x. PMID: 31093920; PMCID: PMC6579039.
5. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in ChronicKidney Disease. Kidney Int. 2022;102(6S):S129–S205.
6. Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA, Atta MG. HIV-associated nephropathy: links, risks and management. HIV AIDS (Auckl). 2018 May 25;10:73-81. doi: 10.2147/HIV.S141978. PMID: 29872351; PMCID: PMC5975615.
7. Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
counsel this patient discussing the pros and cons of transplantation.
Recipient with HIVAN candidate for kidney transplantation needs counselling for.
-Absolute and relative contraindications for kidney transplantation,
-Options available for living versus deceased donor,
-Will need Pre transplant screening for all opportunistic and community acquired
infections and malignancies and proper immunization,
-Details regarding Immunosuppression protocol for induction and maintenance,
-Drug interaction between HAART & CNI and its complications,
-Prophylaxis for opportunistic infection and close surveillance for malignancies after
Transplantation,
–Kidney allograft function / HIV viral control after transplant with close monitoring, with
relative risk of rejection / infection / malignancy post KT,
-Prognosis of Transplant in HIV patients
-Risk of long-term outcomes of renal transplantation in patients with HIVAN,
Pros:
Because availability of c-ART, we can Accept HIV + deceased Donor.
We should Avoid longer wait-list time because of increase mortality on HD
Better survival than being on waiting list on dialysis
No increased Risk of Recurrence of HIVAN as compared to primary FSGS.
Cons:
Some Risk of rejection, DGF is there.
Increase Risk of post-transplant infections and malignancy
Drug interactions between HAART and immunosuppression
Elaborate more on HIVAN? Overview.
-first described in 1984 as a complication of AIDS with Renal disease, although HIVAN may also occur in patients following acute seroconversion.
-HIV-associated nephropathy (HIVAN) is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation secondary to HIV. Pathogenesis.
-It involves direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host. The strong associations of HIV with African ancestry and APOL1 gene polymorphisms illustrate the importance of host genetic factors. Clinical manifestations. –HIVAN presents with heavy proteinuria and a rapid decline in kidney function. Diagnosis.
-The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
-suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
-Kidney biopsy is gold standard for diagnosis of HIVAN.
-There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease.
– Treatment.
All patients with HIV infection should receive ART, regardless of CD4 count.
For patients with HIVAN, ART should be initiated as soon as possible if not already taking. Medication adherence should be assured.
Patients with HIVAN should be treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) for proteinuria and HTN.
There is no role for routine glucocorticoids in patients with HIVAN but in patients whose kidney function is not improving with therapy, the use of glucocorticoids may be considered on a case-by-case basis, weighing the risks of infection and metabolic derangements against the risk of kidney disease progression.
Prognosis.
-The prognosis in patients with HIVAN is poor, even among those treated with ART.
-Many such patients will develop end-stage kidney disease (ESKD).
3-What are the chances of recurrence of HIVAN post-transplantation?
-Insufficient knowledge regarding recurrence of HIVAN but could be in the same way as conventional FSGS, which can be as high as 30% in first grafts
-As the process of FSGS is secondary in nature there is no proven increased Risk of Recurrence post-Transplant
References;
DAqati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998; 18:406.
Winston JA, Bruggeman LA, Ross MD, et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001; 344:1979.
Levin ML, Palella F, Shah S, et al: HIV-associated nephropathy occurring before HIV antibody seroconversion. Am J Kidney Dis 2001; 37: E39
-Atta MG, Choi MJ, Longenecker JC, et al. Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. Am J Med 2005; 118:1288.
Please counsel this patient in discussing the pros and cons of transplantation.
Kidney transplantation is still the best option for an HIV-related ESRD candidate compared to long waiting on dialysis with excellent graft and patient survival based on the available evidence for the last 15 years considering carefully selected HIV candidates who medically fit, with a life expectancy > 5 years and there is no contraindication for the transplantation which means he had persistent low viral load < 50 copies for more than 3 months, C4D count > 200 cells for 6 months, no evidence of active infection including no serious infection for last the 6 months, negative viral screen for HBV, HCV, and VZ, no active malignancy
Good adherence to c ART and tolerated well with no evidence of resistance, three specific conditions should be highlighted and discussed with HIV-positive recipients including the drug-drug interactions after transplantation, the higher rate of rejection including steroid-resistant rejection, and the HIV AN recurrence after transplantation while the opportunistic infection and malignancy found to be of similar rate for non-HIV candidates and usually they will be covered with longer chemoprophylaxis protocols after transplantation
We have to screen the donor for the possibility of HIVAN like proteinuria, hematuria, HIV associated with wide spectra glomerular diseases like HIVAN, IC-mediated nephropathy, infection or drug-induced interstitial nephritis, and TMA, we need to screen for microalbuminuria or assess the grade of proteinuria, and kidney biopsy, HIVAN more in black African American ethnicity with associated APOL1 gene mutation with risk of recurrence after transplantation, reported from some centers like in France series and south Africa but recurrence of HIV nephropathy was not problematic in the US series and they found no correlation between the viral load and the recurrence of HIVAN. Canaud et al describe a rapid deterioration in graft function after the diagnosis of HIVAN if the virus is identified in the podocyte rather than in the tubular cell of the transplanted kidney (4). Will you elaborate more on HIVAN?
HIVAN was first described in 1984 Classic HIVAN, as first defined in the pre-ART era remains to occur among ART-naïve or non-adherent patients, usually of African origin, regardless of the mode of HIV transmission. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load, and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV-positive patients and presenting with heavy proteinuria, mostly in the nephrotic range with progressive renal impairment and ESKD. The diagnosis requires kidney biopsy and typically presents with collapsing focal segmental glomerulosclerosis, Tubulointerstitial inflammation, and microcyst formation in the tubulointerstitial region Tubulointerstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease, the clinical hallmark of HIVAN is heavy proteinuria and enlarged swelling echogenic kidneys by the US, predominant in males with low C4D, high viral load, and microalbuminuria is an early indicator of HIVAN, In USA affect black from African ethnicity in around 3-12%, It has become the third most common cause of ESRD in young people of African descent in the US(3), however with the use of C ART the prevalence of HIVAN has been declined and biopsy finding more with FSGS ( nos ) with low or undetectable viral load and nonspecific histological finding in the biopsy that difficult to be different from aging arteriolosclerosis or APLO1 glomerulosclerosis(5). What are the chances of recurrence of HIVAN post-transplantation?
According to the available evidence from many cohort studies from the US, France, and South Africa regarding the recurrence of HIVAN with diverse results that need further studies in the future focusing on the risk of recurrence related to the time of viral replication in the kidney tissues at the time of treatment of acute rejection
(a flare-up of the viral reservoir in the kidney secondary to aggressive immunosuppression)
Back to the case he is a young HIV-positive recipient with HIVAN as ESRD on dialysis with no doubt will encourage him to go for kidney transplantation from either HIV negative donor or HIV-positive DD provided he accepts the offer and he is medically fit according to the above eligibility criteria and he is adherence to ART with no history of resistance or poor compliance and if he is from African ethnic background better to screen for APOL1 gene mutation, monitor for HIVAN recurrence with proteinuria and work up for proteinuria and consider protocol biopsy after transplantation based on center policy. address the drug-drug interaction and risk of rejection after transplantation and need MDT approach and combined FU with HIV specialist, transplant team regarding the c ART type ( avoid PI) and the viral load and C4D monitoring, prolong chemoprophylaxis for CMV, PJP , fungal infection
References
1. Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11. doi: 10.1159/000526868. PMID: 36816427; PMCID: PMC9936764.
2. Zheng X, Gong L, Xue W, Zeng S, Xu Y, Zhang Y, Hu X. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther. 2019 Nov 20;16(1):37.
3. Ma L, Divers J, Freedman BI. Mechanisms of injury in APOL1-associated kidney disease. Transplantation. 2019;103(3):487–492.
4. Canaud G, Dejucq-Rainsford N, Avettand-Fenoel V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. Journal of the American Society of Nephrology : JASN. 2014;25(2):407–19.
5.Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501
Please counsel this patient discussing the pros and cons of transplantation.
I will counsel him on the following points:
Firstly, & most importantly, that HIV itself is not a contraindication for kidney transplantation (1B), & that transplantation has morbidity & mortality benefits, though associated with increased rate of DGF and rejection as compared to ESRD due to other causes.
Secondly, that being HIV-positive, he will be wait-listed only if he is fulfilling the following conditions:
Adherence with treatment prescribed to control the virus (cART therapy).
The CD4+ T cell counts are >100 cells/μL & have been stable during the preceding 3 months.
Undetectable viral load in the last 6 months.
No opportunistic infections have occurred during the last 6 months.
No H/O progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.
============================= Will you elaborate more on HIVAN?
HIVAN is most prevalent in patients who receive ART late after initial diagnosis, & is a major cause for CKD in developing countries. Organ failure develops more quickly than in high income nations due to high incidence of infection-related nephropathies & a lack of secondary preventative measures.
Regardless of the method of HIV transmission, classic HIVAN, as it was first defined in the pre-ART period, continues to occur among ART-naive or non-adherent patients, typically of African heritage.
High viral load, low CD-4 count, & apoliprotein-L1 (APOL1) genetic variant have all been associated with an increased clinical risk for developing HIVAN in the native kidneys of HIV positive individuals.
Proteinuria in the nephrotic range, increased renal echogenicity on US, & a kidney biopsy are used to confirm the diagnosis.
HIV positive patients also suffer from CKD secondary to non-communicable diseases (DM & HTN).
HIV-related CKD has become the third most common cause of ESRD in young people of African descent in the US.
Podocytopathy or immune complex-mediated glomerular disease are two common manifestations of HIV in the kidney. The podocytopathy can manifest as FSGS or MCD & diffuse mesangial hypercellularity.
In 2008, an HIV-positive donor transplant program was launched in South Africa.
For around 20 years, TX programs in the USA have used HIV-negative donors, & more recently, the Hope Act has allowed for the use of HIV-positive donors as well.
In most centers HIV positive patients had been transplanted with HIV negative living & DD. Only one centre had reported long-term outcomes using HIV positive DD with several new centers now embarking on this practice as part of the HOPE act in the USA as well as some centers in Europe.
Specific infection screening considerations in HIV positive TX HPV screening post transplantation:
Post-TX IS may make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection.
Prophylactic therapy:
Prophylaxis against PCP & CMV is similar to regimens used at most centers for HIV negative recipients.
Vaccinations prior to transplant:
Pneumococcal vaccine given to all patients on the waiting list pre-TX.
Hepatitis A&B vaccine, if indicated, should be given before the transplant.
Influenza vaccine once yearly.
HZV vaccination in high-risk patients (>50 years old).
HPV vaccine should be given in selected patients, usually under the age of 45 years.
All patients have to be up to date with DPT & MMR vaccinations before transplantation.
Vaccinations post-transplant:
Annual influenza vaccination is recommended.
Use of live virus vaccine not recommended (MMR should not be given post-transplant)
It is recommended to wait 3 to 6 months after transplant before giving vaccines.
If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment.
Interaction between protease & non-nucleoside reverse transcriptase inhibitors with the CNI & mTOR inhibitors.
Variable drug levels between patients & often CNI dosages have to be significantly increased or decreased as a result of these drugs on the cytochrome P450 enzyme.
============================= What are the chances of recurrence of HIVAN post-transplantation?
Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence.
HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients.
Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney.
References
Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kathryn Manning, Peter Chin-Hong, Peter Stock, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies, Transplantation. 2021 July 01; 105(7): 1492–1501. doi:10.1097/TP.000000000000 3485.
British Transplantation Society Guidelines. Kidney & Pancreas Transplantation in Patients with HIV March 2015 [Minor Revision January 2017]
Thank you so the recurrence if it happens de novo has no correlation with:
R viral load.
D viral status.
Is there a relation with IS ,induction choice.
Drug interactions with ART.
Please counsel this patient discussing the pros and cons of transplantation.
The HIV per se is not a contraindication for kidney transplantation, however the viral status should be controlled by a c-ART ( compliant to treatment, CD4 >100 cells/µL- ideal > 200 cells/ µL for the last 3 months, undetectable HIV RNA in the last 6 months, no opportunistic infection in the last 6 months, no PML, lymphoma or intestinal cryptosporidiosis) and an infectious disease specialist to be included in management pre and post transplantation for choosing best treatment and avoiding drug-drug interaction. HIV viremia post transplant is possible, but controlled by c-ART.
The risk of opportunistic infection and mortality is common in the first 6 months post transplant and may be fatal.
Viral screen is a must, co infection with hepatitis C has a deleterious outcome: Evidence of current vaccine induced or natural immunity to: Diphtheria, tetanus and pertussis (DTP), Measles, mumps and rubella (MMR), Pneumococcus, Haemophilus influenza, Meningococcus B, Influenza, VZV, Hepatitis A and, Hepatitis B (for HBsAg, HBcAb, negative patients), Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV, and Strongyloides stercoralis infection prior to transplantation
PROS: Transplantation improves quality of life and survival compared of being on HD. Transplantation can be from a living or cadaveric donors with special criteria for selection of donors. Transplantation in these patients can be safe when the HIV is controlled by c-ART.
CONS: There is an increased risk of acute rejection in HIV patients. There is an increased risk of infections especially in the first 6 months, and may be fatal. There is an increased risk of malignancy. There is an increased risk of delayed graft function. Requiring multidisciplinary team (infectious disease, pharmacologist, transplant physician) concerning drug-drug interaction.
Will you elaborate more on HIVAN? HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS), accompanied by microcystic tubular dilatation, Tubuloreticular inclusions, pseudocrescent formation and interstitial inflammation. Africans are more commonly experiencing HIVAN, with APOL1 risk variants having higher incidence. c-ART reduce the incidence of HIVAN, decrease progression to ESRD, and improve survival.
The pathogenesis of HIVAN is hypothesized to involve several factors: 1. Infection of kidney epithelial cells by HIV and expression of HIV genes within nfected kidney cells. 2. Host factors, including genetic susceptibility. Clinical manifestations: Hematuria, hypertension, edema, rapidly progressive GN, nephrotic range proteinuria, usually in patients with CD4 T cell < 200. DDx: other viral infections- Corona viruses, light chain disease, MPGN, lupus nephritis, crescentic GN. Diagnosis: only by kidney biopsy. Treatment: c-ART + ACEi/ARBs+/- SGLT2i + statins, No rule for steroids Transplantation: there is an increased risk of HIVAN recurrence after renal transplantation, and marked increased risk of acute rejection. What are the chances of recurrence of HIVAN post-transplantation? There is an increased risk of HIVAN recurrence after renal transplantation, and marked increased risk of acute rejection (3 folds more than non HIV infected patients) or lupus like glomerulonephritis with rapidly progressive GN.
References: (1) Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int. 1999 Dec;56(6):2203-13. doi: 10.1046/j.1523-1755.1999.00769.x. PMID: 10594796. (2) Selhorst P, Combrinck CE, Manning K, Botha FCJ, Labuschagne JPL, Anthony C, Matten DL, Breaud A, Clarke W, Quinn TC, Redd AD, Williamson C, Muller E. Longer-Term Outcomes of HIV-Positive-to-HIV-Positive Renal Transplantation. N Engl J Med. 2019 Oct 3;381(14):1387-1389. doi: 10.1056/NEJMc1903013. PMID: 31577883. (3) HIV and Kidney Transplantation lecture,By Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool –UK (4) Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Thank you for this overview. With the risk of opportunistic infections do these patients require different antimicrobial prophylaxis post transplants compared to those with
HIV-ve recipients?
You referred to increased risk of HIVAN recurrence, can you support your answer with an appropriate reference?
Please counsel this patient, discussing the pros and cons of transplantation, and elaborate more on HIV/AIDS.
In patients with HIV, pre-transplant evaluation takes into consideration the risk of recurrence and the risk of complications. Evaluation includes pre-transplant assessment of viral load, immunosuppressive management, post-transplant prophylaxis, immunizations, rejection risk, and delayed graft function.
HIV-positive kidney transplantation can minimize AR, but more research is needed to optimize immunosuppressive medications. Many end-stage renal disease patients choose kidney transplantation. Kidney transplants can extend life and enhance quality. Kidney transplant patients do not require dialysis.
HIV-positive individuals with stable ART regimens and CD4 counts above 200 cells/mm3 should be transplanted. Nevertheless, only internationally experienced centers should transplant HIV-positive recipients with virus loads under 200 cps/mL.
Opportunistic diseases and untreated neoplasms should not be transplanted, although fully treated tuberculosis should. Pre-transplant screenings should include tuberculosis, syphilis, and hepatitis C. Before transplant, treat or screen for HBV/HCV co-infection.
In this group, the benefits of kidney transplantation include an improvement in quality of life.
The replacement kidney will aid in restoring the body’s metabolism and enhancing blood circulation, enabling the body to better process nutrients and live a healthy life.
Disadvantages include delayed graft function, the chance of graft rejection and loss, and an increased risk of hospitalization. Other side effects include infectious problems and possibly drug-drug interactions.
What are the chances of recurrence of HIV/AIDS post-transplantation?
The risk of recurrence increases in settings of uncontrolled infection.
There are several histological forms of HIV-related kidney disease. The most common form is the collapsing form of FSGS. Other forms include immune complex-mediated glomerular disorders, HIVAN-related tubulointerstitial damage, and vascular-dominant nephropathies.
In patients with controlled HIV disease and a low viral load, the recurrence of HIVAN is negligible.
Thank you Dr Habli
I can see that you concentrated on the HIV recurrence and opportunistic infections. What about the overall graft and patient survival in the presence of these risks. Is it hugely different from general population or close to it with the benefits outweigh these risks. Please quote the appropriate supporting references.
Please counsel this patient discussing the pros and cons of transplantation.
Pre-transplant testing and immunization, immunosuppressive protocol, post-transplant prophylaxis, risk of rejection, prognosis, long-term results, post-transplantation problems, HIV infection, and delayed graft function.
KT can be successful in HIV+ patients, but further studies are needed to optimize immunosuppressive therapy regimens to reduce AR after transplantation.
Kidney transplantation is the treatment of choice for many pateints with end-stage kidney disease.
A successful kidney transplant can improve your quality of life and reduce your risk of dying.
In addition, pateints who undergo kidney transplantation do not require hours of dialysis treatment.
Ideally, patients who are eligible to get a kidney transplant do so before ever starting on dialysis.
Patient selection for HIV positive transplantation
HIV positive patients should be selected for transplantation according to standard selection criteria, such as virally suppressed, stable ART regimen, and CD4 count above 200 cells/mm3.
However, transplantation of HIV positive recipients with viral loads less than 200 cps/ml should be limited to centres with abroad experience.
Patients with fully treated tuberculosis should be considered for transplantation, while those with opportunistic infections and neoplasms without effective medical therapy are excluded.
All potential recipients should be screened for tuberculosis, syphilis and hepatitis C pre-transplant.
Treatment/screening for co-infection for HBV/HCV should be done prior to transplant.
The pros:-
Improve your quality of life.
The new kidney will help restore the body’s metabolism and improve blood circulation, allowing the body to handle nutrients better and live a healthy life.
The cons ;-
Delayed graft function (DGF), AR, graft loss and days spent hospitalized in the first year after KT as well as a trend towards lower mortality.
Acute rejection.
Young age, heavy proteinuria before transplant, and rapid progress of primary FSGS are independent risk factors for recurrent FSGS.
HIV-related nephropathy is a major cause of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from AKI and CKD.
A full virologic cure is only possible with complete eradication of the viral reservoir in the kidney.
Renal disease associated with HIV infection is primarily a glomerular dominant disease, classified into two main categories: podocytopathies and immune complex-mediated disease.
Secondary causes should be sought in post-infectious glomerulonephritis.
HIV-associated nephropathy incidence peaked in the mid-1990s, but has declined due to increased use of combined anti-retroviral treatments.
HIV-Associated Nephropathy is caused by the expression of HIV-1 genes in the kidney epithelial cells, which is mediated via transfer from leukocytes and phagocytosis of apoptotic CD4+ T cells.
Polymorphisms in APOL1 result in an increased risk of HIVAN.
HIV-Associated Immune Complex Kidney Disease
HIV-associated immune complex kidney disease is caused by co-infection with hepatitis B and C, but the mechanism and relevance of post-antiretroviral therapy is unknown.
HIV-Associated Thrombotic Microangiopathy
Thrombotic microangiopathy is caused by exposure to circulating viral proteins combined with medications, proinflammatory molecules, and antiphospholipid antibodies.
Histopathology
HIV-associated nephropathy is characterized by collapsing glomerulopathy and tubulointerstitial disease, with diffuse effacement of podocyte foot process and endothelial tubular inclusions.
History and Physical
HIV-associated nephropathy is characterized by a rapid decline in GFR and proteinuria, but other manifestations are uncommon.
Evaluation
Screening for HIV nephropathy in HIV positive patients should include serum creatinine and estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline when ART is initiated or changed, and at least twice a year in stable patients infected with HIV.
Imaging modalities, such as ultrasonography of the kidneys, may be useful in specific settings, but a kidney biopsy is often the only means of achieving a definitive diagnosis.
CART induced nephropathy is more common than HIVAN, presenting with CD4 count <200 cells/mm, viral load >400 copies/mL, rapid decline in renal function, proteinuria >300 mg/24h, hyaline or proteinaceous casts on urinalysis, and large-sized kidneys with intense cortical echogenicity.
Treatment / Management
HIVAN is associated with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, so combined antiretroviral therapy is the mainstay of treatment.
Renin-angiotensin-aldosterone system (RAAS) blockade is also important, and steroids can be added as an adjunct.
It is important to adjust cART therapy to renal function, and renal replacement therapy remains the mainstay.
Differential Diagnosis
HIV-associated immune complex kidney disease
Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)
Amyloidosis
Minimal change disease
Postinfectious glomerulonephritis
Thrombotic microangiopathy
Diabetic nephropathy
Immunoglobulin A nephropathy
Membranous glomerulopathy
Prognosis
HIVAN has a favorable prognosis, but patients with HIVAN consistently do worse than those with other causes of renal disease.
Complication
HIVAN can lead to CKD, ESRD, hypertension, and lower extremity edema.
Deterrence and Patient Education
HIV-associated nephropathy is an aggressive disease that can lead to end-stage renal disease, so patients should be encouraged to be compliant with antiretroviral medications and follow up with their primary care clinician and nephrologist on a regular basis.
Pearls and Other Issues
Combined antiretroviral therapy is the mainstay treatment for HIVAN, but other etiologies are more common due to cART and improved survival.
An interprofessional team approach should be used to improve patient outcomes, including frequent renal function testing and biopsy.
CD4 count and viral load should be taken into account for cART initiation.
HIV and Kidney Transplantation By Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool -UK
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013;62(2):335-338. doi:10.1053/j.ajkd.2013.01.010
Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int 92: 461–469, 2017
Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018 May;27(3):144-152.
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Thank you, Mahmoud What are the other forms of HIVAN? You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
Many thanks for your suuport and advice Prof.Halawa
What are the other forms of HIVAN?
HIV-related kidney diseases fall under four pathologic classifications :
Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases
Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis.
============================================================ Has it been reported in the Caucasian population?
Two coding sequence variants in the APOL-1 gene can increase the risk of HIV-infected people developing HIVAN by ∼50%.
These variants encode a secreted lipid-binding protein named apolipoprotein L1, which is lethal to Trypanosoma brucei rhodesiense.
These findings explain why HIVAN is seen in patients of African ancestry and why blacks from Northeast Africa or Ethiopia do not develop HIVAN.
APOL1 has several roles, including transport of lipids and cholesterol, formation of ion channels, innate immune responses, cytolysis and autophagic cell death.
Moro O Salifu, MD, MPH, MBA, MACP Associate Professor, Department of Internal Medicine, Chief, Division of Nephrology, Director of Nephrology Fellowship Program and Transplant Nephrology, State University of New York Downstate Medical Center
1-Please counsel this patient discussing the pros and cons of transplantation. Recipient with HIVAN candidate for kidney transplantation should be counseled for;
– Consent and confidentiality before transplantation,
-Absolute and relative contraindications for kidney transplantation,
-Choice of living versus deceased donor, -Pre transplant screening and immunization,
-Immunosuppression protocol for induction and maintenance,
-Drug interaction between HAART & CNI, -Prophylaxis after Transplantation, –Monitoring after transplantation; Kidney allograft function / HIV viral control,
-Protocol of biopsies in high risk recipient with graft dysfunction post KT, -Risk of rejection / infection / malignancy post KT, -Prognosis of HIVAN and chances of recurrence after transplantation, -Risk of long-term outcomes of renal transplantation in patients with HIVAN,
-Post-transplantation complications; HIV infection of the allograft / Opportunistic infections / Delayed graft function / Retransplantation . Pros: (Because availability of c-ART) -Accept HIV + deceased Donor –Avoid longer wait-list time and risk of death on dialysis
-Increase kidney donor pool
–Better survival than being on waiting list on dialysis Cons: -Risk of rejection , DGF -Risk of post-transplant infections, malignancy -Drug interactions between HAART and immunosuppression -Risk of recurrence of HIVAN post KT 2-Will you elaborate more on HIVAN? Overview; -The classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS, although HIVAN may also occur in patients with less advanced HIV infection or following acute seroconversion. -HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation. Pathogenesis; -The pathogenesis of HIVAN is hypothesized to involve direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host. -The strong associations of HIV with African ancestry and APOL1 gene polymorphisms illustrate the importance of host genetic factors. Clinical manifestations; –HIVAN classically presents with heavy proteinuria and a rapid decline in kidney function in a person with advanced HIV disease. Diagnosis; -The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function. -Our suspicion is particularly high if the patient has a CD4 cell count <200 cells/microL, HIV viremia, and/or has a history of nonadherence to antiretroviral therapy (ART). -Kidney biopsy is currently the only way to establish a definitive diagnosis of HIVAN. Histologic diagnosis. -There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease. -If a kidney biopsy cannot be performed safely, we manage patients with suspected HIVAN similarly as those with biopsy-proven HIVAN. Treatment; Approach to the treatment of HIVAN is as follows: -All patients with HIV infection should receive ART, regardless of CD4 count. -For patients with HIVAN who are not already receiving ART, ART should be initiated as soon as possible. -For patients who are already receiving ART, medication adherence should be assessed. -Patients with HIVAN who have proteinuria and/or hypertension should be treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB). -This approach is similar to that for patients with proteinuric chronic kidney disease (CKD). -Patients who have persistent proteinuria in spite of treatment with an ACE inhibitor or ARB may benefit from addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor. -There is generally no role for routine glucocorticoids in patients with HIVAN. -In patients whose kidney function is not improving with therapy, the use of glucocorticoids may be considered on a case-by-case basis, weighing the risks of infection and metabolic derangements against the risk of kidney disease progression. Prognosis; -The prognosis in patients with HIVAN is poor, even among those treated with ART. -Many such patients will develop end-stage kidney disease (ESKD). 3-What are the chances of recurrence of HIVAN post-transplantation? -Insufficient knowledge regarding recurrence of HIVAN but could be in the same way as conventional FSGS, which can be as high as 30% in first grafts -could be just histological without significant change in the kidney function. – cART may not have any effect on the recurrence of HIVAN. -Biopsy, if there is any evidence of Graft dysfunction. Monitoring Allograft function; -Biopsy if DGF or graft dysfunction -(In high risk recipients) follow Protocol biopsies at 1 month, 3 months , and 12 months. References; -Rao TK , Filippone EJ , Nicastri AD ,et al: Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome . N Engl J Med 1984;310:669. -Gardenswartz MH , Lerner CW , Seligson GR , et al: Renal disease in patients with AIDS:a clinicopathologic study . Clin Nephrol 1984; 21:197. -Winston JA , Bruggeman LA , Ross MD , et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344:1979. -Levin ML , Palella F , Shah S , et al : HIV-associated nephropathy occurring before HIV antibody seroconversion. Am J Kidney Dis 2001; 37:E39 -DAqati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998; 18:406. -Atta MG , Choi MJ , Longenecker JC , et al.Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. Am J Med 2005; 118:1288.
Thank you, Mohamed Do you mean the risk of recurrence of 30%? Remember, the FSGS in HIVAN is a secondary FSGS with no chance to recur if the primary cause was treated.
Thanks, our Prof; I mean: there are insufficient knowledge regarding recurrence of HIVAN and like FSGS in high recurrence rate in first grafts. Retransplantation in HIVAN -Patients whose first allograft fails can be considered for retransplantation; second kidney transplants now comprise 13.1 % of the general waiting list . One study examined outcomes for 22 patients with HIV who were retransplanted, compared with 4127 HIV-negative matched controls. Unfortunately, in this analysis, patients with HIV who had a second transplant had a 3.1-fold higher risk of death and a 1.96-fold increased risk of allograft loss. References; -Hart A, Smith JM, Skeans MA , et al :OPTN/SRTR 2015 Annual Data Report:Kidney Am J Transplant 2017: 17 Suppl 1:21. -Shelton BA, Mehta S, Sawinski D, et al: Increased Mortality and Graft Loss With Kidney Retransplantation Among Human Immunodeficiency Virus (HIV)-Infected Recipients.Am J Transplant 2017; 17:173.
Counselling and discussion
According to evidence, a person living with HIV (PWH) should get solid organ transplantation as normal medical care.
The HIV Organ Policy Equity (HOPE) Act also declared that PWH are eligible to become donors.
The recipient must have stable disease for at least the previous six months, have good compliance, viral suppression, CD4 > 200, and be free of opportunistic infections or cancers in order to be eligible for transplantation.
Survival rate is after transplants than hemodialysis.
After transplantation, further care may require close HIV RNA monitoring and immunizations; however, the majority of management is identical to that for non-HIV patients.
Although co-infections with other viruses, such as HCV/HBV, have to be checked out, transplantation remains preferable to dialysis overall despite the increased risk of infections, delayed graft function, and rejection rates.
HIVAN
One of the main factors contributing to CKD and ESKD in black people is HIVAN. Low CD4 count and high viral load are significant risk factors. CLINICAL FEATRUE
Proteinuria, nephrotic syndrome, renal insufficiency, and hypertension are examples of possible clinical characteristics. PATHOLOGY AND TREATMENT
Loss of podocytes, abnormal stem cell replenishment, tubular damage, and microcystic tubular dilatation are pathological characteristics.
The majority of treatments are conservative, such as cART, ACEI/ARBS, statins, and in certain situations, a steroid trial. What are the chances of recurrence of HIVAN post-transplantation
Even in patients with undetectable viral levels who are receiving antiretroviral medication, HIV may still be possible to infect kidney allograft.
High incidence of DGF in recipients with HIV (42.5%) and its detrimental effects on allograft survival (hazard ratio [HR] 1.86, 95% CI] suggest that infections are more likely to be connected to the post-transplant immunosuppressive state than to HIV infection.
Re-transplantation may be explored for patients whose initial allograft fails; second kidney transplants presently account for 13.1% of the overall waiting list.
Thank you, Muhammed What are the other forms of HIVAN? Has it been reported in the Caucasian population? What about the recurrence after transplantation?
In addition to lesions directly linked to intrarenal HIV gene expression, the spectrum of renal pathology in HIV-positive people also includes lesions linked to comorbidities, treatment side effects, immunological dysregulation, and co-infections.
There are four pathologic categories for HIV-related kidney disorders.
HIVAN and immune complex-mediated glomerular disorders are examples of glomerular-dominant nephropathies.
Nephropathies with a tubulointerstitial predominance
HIVAN-related tubulointerstitial damage, acute tubular injury brought on by ART, tubulointerstitial nephritis brought on by medications other than ART, and direct renal parenchymal infection by viral, bacterial, or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis
HIV-associated chronic kidney disease (CKD) varies geographically and depending on the definition used. In North America and Europe, CKD prevalence ranges from 4.7% to 9.7%, with a change in definition to include reduced eGFR and/or proteinuria. In the US, the prevalence of CKD increases to 15.5%.
Insufficient data regarding reoccurrence of HIVAN
Rosenberg AZ, Naicker S, Winkler CA, Kopp JB. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat Rev Nephrol. 2015 Mar. 11 (3):150-60.
Swanepoel CR, Atta MG, D’Agati VD, Estrella MM, Fogo AB, Naicker S, et al. Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018 Mar. 93 (3):545-559.
Diana NE, Naicker S. Update on current management of chronic kidney disease in patients with HIV infection. Int J Nephrol Renovasc Dis. 2016. 9:223-234.
Transplantation in HIV positive patients.
Its considered as safe and of good prognosis comparable to non HIV infected allograft recipients. Selective criteria must be implicated in those patient in order to optimize the safety and minimize adverse outcome . The implication of ART has improved outcome significantly post transplantation .
Minimizing the risk of Activation of HIV post transplantation resulting from immunosuppression status .
Criteria for selection of HIV positive transplant candidate:
1] CD4 of more than 200
2] HIV viral load of less than 50 RNA copies /ml.
3] compliant and adherent to ART medications.
4] No history of active infection such as aspergillosis, active CMV, incomplete treatment of TB.
5] No AIDS -defining illnesses.
HIVN:
Its representing glomerular disease in the form of podocytopathy of either Minimal change disease or classically collapsing FSGS, its commonly encountered in poorly controlled HIV disease with high HIV RNA copies and low CD4 count. Relapse after transplantation is reported anecdotally and there is no consensus about risk of recurrence. Each case must be taken as per its merits. IN general, outcome of transplantation is favorable for HIVN patients
Evidence suggested that, solid organ transplantation is a standard of care for a person living with HIV (PWH)
HIV Organ Policy Equity (HOPE) Act, stated that PWH can be donors
Eligibility criteria for transplantation are: The recipient must be having stable disease at least over the last 6 months with good compliance, viral suppression, CD4 > 200, and no opportunistic infections or malignancies.
Transplantation offers better survival than hemodialysis
Extra care may involve close monitoring for HIV RNA after transplantation, vaccinations otherwise most of the management are similar to non-HIV recipients
Co-infections with other viruses needed to be ruled out e.g., HCV/HBV
Studies reported, more risk of infections, delayed graft function, and rejection rates compared to non-HIV recipients but overall, transplant is still better than dialysis
Few centers in USA are still considering HIV is absolute contraindication for transplantation and this may result in longer waiting list time
Q2.
HIVAN is one of the leading causes of CKD and ESKD in black people
It was very common before the era of Cart but it is rarely seen these day
Important risk factors are high viral load & low CD4 count
Clinical features may include proteinuria, nephrotic syndrome, renal insufficiency and hypertension
Pathological features are; podocytes loss, abberrant stem cell replenishment , tubular injury, and microcystic tubular dilatation
Treatment is mainly conservative e.g., cART, ACEI/ARBS, statins, and trial of steroid in some cases
Q3.
No enough data to tell
May be the same as primary FSGS ~ 30%
May be histologic recurrence with no clinical manifestations
May not respond to Cart
Source:
-BTS guidelines 2018
-Organ transplantation in persons with HIV by Rebecca N. Kumar and Valentina Stosor
Has it been reported in the Caucasian population?
You mentioned a recurrence rate of around 30% similar to FSGS, but the FSGS associated with HIV is a secondary one which should not recur if the primary cause was successfully treated
Please counsel this patient discussing the pros and cons of transplantation. Pros:
Better quality of life
Better survival than being on waiting list on HD/PD
Good graft survival (The largest prospective study to date included 150 HIV-positive patients and reported patient and graft survival rates of 88% and 74% at three years
Recent studies haveGraft survival during the 1-year and 3-year mark was 90% and 74%, respectively)
Cons:
More chances of rejection
More post-transplant infections
Need for more post-transplant prophylaxis
Increased drug interactions between HAART and immunosuppression
More chances of post-transplant malignancies
Will you elaborate more on HIVAN? Introduction
Renal disease associated with HIV infection is primarily a glomerular dominant disease that is further classified into two main categories: podocytopathies and immune complex-mediated disease.
HIVAN is a podocytopathy
These are characterized by extensive podocyte foot process effacement and proteinuria mediated by direct HIV infection of renal epithelial cells, intrarenal viral gene expression, and dysregulation of host genes.
Definition:
HIV-associated nephropathy is defined as a collapsing glomerulopathy and associated tubulointerstitial disease, which may include tubular microcysts and inflammation of the interstitium.
Diffuse effacement of podocyte foot process and endothelial tubular inclusions are mainstays when examined by electron microscopy.
Staining for IgM, C3, and C1q in collapsed segments and mesangial areas is common by immunofluorescence
Pathophysiology:
The expression of HIV-1 genes in the kidney epithelial cells is required for the development of HIVAN.
The mechanism by which HIV infects renal epithelial cells remains unclear.
Macrophages and lymphocytes appear to be vectors necessary for renal epithelial cell transmission of HIV.
Among these are CD209 antigen (DC-SIGN), which mediates HIV infection of dendritic cells, and lymphocyte antigen 75 (DEC-205), which may directly contribute to infection of renal tubular epithelial cells.
It appears likely that the infection of renal tubular epithelial cells by HIV is mediated via transfer from leukocytes.
Phagocytosis of apoptotic CD4+ T cells has also been proposed as a possible mechanism by which HIV accesses renal cells.
The HIV proteins Vpr and Tat circulate in plasma and through proteoglycans, and lipid rafts have access to podocytes.
Mangement:
Management: Combined antiretroviral therapy (Mainstay) as it has been shown to reduce the likelihood of progression into ESRD.
Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) is also important since it has been shown to improve renal survival and should be considered as an adjunct to cART in HIVAN.
In patients with refractory renal impairment after cART and RAAS blockade treatment, steroids can be added as an adjunct
What are the chances of recurrence of HIVAN post-transplantation?
Recent studies on renal transplantation in patients with HIVAN have shown favorable results. Graft survival during the 1-year and 3-year mark was 90% and 74%, respectively
Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV positive patients. Diagnosis is confirmed by a nephrotic range proteinuria, and increased renal echogenicity on ultrasound and a kidney biopsy
In the South African group of 51 transplants, 12 patients were reported to have some HIVAN related changes on biopsy, but only 2 patients lost their grafts as a result
Melendez Rivera JG, Hashmi MF. HIV Nephropathy. [Updated 2022 Aug 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Rivera FB, Ansay MF, Golbin JM, Alfonso PG, Mangubat GF, Menghrajani RH, Placino S, Taliño MK, De Luna DV, Cabrera N, Trinidad CN. HIV-associated Nephropathy in 2022. Glomerular Diseases. 2022. Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
BTS guidlines: Kidney & Pancreas Transplantation in Patients with HIV
Thank you, Abhijit What are the other forms of HIVAN? You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population? What about the recurrence after transplantation? Any evidence?
Please counsel this patient in discussing the pros and cons of transplantation.
Pros:
After kidney transplantation, the results of 150 HIV-positive patients were reported in the biggest prospective observational study ever carried out; kidney allograft and patient survival estimate at 1 and 3 years were 90.4 and 73.7 and 94.6 and 88.2%, respectively. Since viral suppression was seen in every patient and their CD4 cell levels were at least 200 cells/ml
Before the transplant, HIV was treated with a combination of ART, and anti-infective prophylaxis was used after the transplant as well.
Control was quite good, and there were just a few instances of opportunistic infections.
cons:
HIV patients had more bacterial infections.
individuals who received ATG or other lymphocyte-depleting agents
PWH also had significant rates of delayed allograft function (hemodialysis in the post-transplant interval), although this did not predict graft failure. Ultimately, HIV-positive kidney transplant patients had allograft rejection rates two to three times greater than the overall kidney transplant group, and rejection predicted allograft failure.
Will you elaborate more on HIVAN?
Even without edema, HIV patients with nephrotic-range proteinuria and rapidly deteriorating kidney function should be suspected of HIVAN. ʼ (ART). HIVAN should be investigated in individuals with lesser proteinuria
HIVAN can only be diagnosed by kidney biopsy since clinically suspected HIVAN patients frequently have an alternate histologic diagnosis. HIVAN cannot be distinguished from other glomerular diseases, including HIV-associated kidney disease, by laboratory tests. If a kidney biopsy is unsafe, we treat suspected HIVAN like biopsy-proven HIVAN.
What are the chances of recurrence of HIVAN post-transplantation?
Despite ART and adjuvant medications such as renin-angiotensin inhibitors and SGLT2 inhibitors, some HIVAN patients develop ESKD and need dialysis or kidney transplants.
Since the advent of effective ART, HIV-positive dialysis patients have improved survival rates, although mortality remains high. HIV-related dialysis concerns are addressed individually.
HIVAN and ESKD patients may undergo transplantation, however, the allograft may recur. HIV kidney transplantation includes HIV-positive donor organs.
References: Kumar, R. N., & Stosor, V. (2020). Organ transplantation in persons with HIV. AIDS, 34(8), 1107–1116).
Sawinski D, Forde KA, Locke JE, et al. Race but not Hepatitis C co-infection affects the survival of HIV+ individuals on dialysis in contemporary practice. Kidney Int 2018; 93:706.
Thank you, Isaac What are the other forms of HIVAN? You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population? What about the recurrence after transplantation? Any evidence?
Certain HIVAN patients may still develop ESKD despite receiving ART and adjuvant drugs such as renin-angiotensin inhibitors and SGLT2 inhibitors. These patients will need either dialysis or a kidney transplant.
Even though there has been significant progress made in the development of effective ART, the overall mortality rate among HIV-positive dialysis patients is still rather high. Concerns with dialysis that are connected to HIV are handled separately.
Transplantation is an option for HIV-AN and ESKD patients; however, there is a chance that the allograft may fail. Transplantation of HIV-infected kidneys requires the use of HIV-positive donor organs.
Please counsel this patient discussing the pros and cons of transplantation.
Pros · Best modality of RRT compared to PD and HD. · Better graft and patient survival (at 1 and 3 years 95 and 88 percent allograft survival 90 and 74 percent) compared to other modalities. · Improve quality of life. Cons
· Higher risk of allograft rejection
· Increased risk of infections
· Drugs interaction with Immunosuppressant
· Risk of malignancies.
Will you elaborate more on HIVAN?
More common in individual from African descent, presence of APOL1 risk variants is at high risk of HIVAN. Introduction of combination ART has reduced incidence of HIVAN. HIVAN is a major cause of ESKD in people living with HIV. [3] HIV directly infects glomerular and kidney tubular epithelial cells in HIVAN. The strong association between HIVAN and African ancestry indicates that host genetic factors are also important. The mechanism through which variants in APOL1 promote HIVAN and FSGS has not been fully demonstrated. HIVAN usually manifest clinically with;
· Proteinuria usually nephrotic range
· Decline in GFR
· Hypertension and
· Edema
Diagnosis;
Kidney biopsy is required to establish HIVAN
Treatment
The mainstay of treatment is ART along with other supportive therapies
· ART should be initiated as soon as possible in those who are not taking it already; compliance should be assessed in those who are already on ART. Patients who are adherent but increasing viral load should be tested for Drug resistance.
· ACEIs/ARBs
· SGLT2 inhibitors
· Steroids should be considered in HIVIC only.
What are the chances of recurrence of HIVAN post-transplantation?
There is no concrete data to answer this question but inferring from various studies it would be sensible to have closely monitor recipients for; · Proteinuria · Viral load · GFR · Drugs level and · Biopsy in order to see for recurrence.
References
1. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients [published correction appears in N Engl J Med. 2011 Mar 17;364(11):1082]. N Engl J Med. 2010;363(21):2004-2014. doi:10.1056/NEJMoa1001197
2. Gathogo E, Harber M, Bhagani S, et al. Impact of Tacrolimus Compared With Cyclosporin on the Incidence of Acute Allograft Rejection in Human Immunodeficiency Virus-Positive Kidney Transplant Recipients. Transplantation. 2016;100(4):871-878. doi:10.1097/TP.0000000000000879
3. Razzak Chaudhary S, Workeneh BT, Montez-Rath ME, Zolopa AR, Klotman PE, Winkelmayer WC. Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrol Dial Transplant. 2015;30(10):1734-1740. doi:10.1093/ndt/gfv207
Please counsel this patient discussing the pros and cons of transplantation.PRO
●RTx is the treatment option for fit patient with life expectancy is >5 years.
●in one study ; patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%.
●Quality of life is better
●Mortality and morbidity and complications of dialysis is higher
CONS
□Renal transplantation in HIV pos patients carries higher risk for acute rejection
□A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively.
□Opportunistic infection remains a major cause of complications and death . (Viral – hepatitis viral- bacterial- TB- …. )
We should discuss the reason of HIVAN
♧ is it delaying of antiviral treatment ?
♡Incompliance for treatment ?
◇Genotyping resistance of viruses ?
This point is very necessary because it may predict the prognosis of graft survival later
Will you elaborate more on HIVAN?●HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS
●Histologically, HIVAN is a collapsing form of (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation
●In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
●The introduction of combination (ART) substantially reduced the incidence of ESKD attributed to HIVAN
The pathogenesis several factors:
●Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells
●Host factors, including genetic susceptibility
Clinical manifestations
○Nephrotic-range proteinuria
○Rapid decline in kidney function
○Hematuria – 45 to 75 percent
○Hypertension – 12 to 26 percent
○Edema – 22 to 59 percent
Establishing the diagnosis — Kidney biopsy
Initial therapy
●Antiretroviral therapy for all patients
●Additional therapies for proteinuria or hypertension
ACE inhibitors or ARBsSGLT2 inhibitorsWhat are the chances of recurrence of HIVAN post-transplantation?I dont found a study that shows that prevalence of recurrence HIVAN
However, the chances of recurrence of HIVAN depends on
●The compliance with antiviral therapy
●CD 4 less than 200, especially if their CD4 count is less than 50 cells/µ
●the development of acute rejection therefore induction therapy using ATG, rituximab, or plasma- exchange
REFERENCES
Professor Halawa lecture
Kidney & Pancreas Transplantation in Patients with HIV
Thank you, Ghalia What are the other forms of HIVAN? You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
Please counsel this patient discussing the pros and cons of transplantation.
Pros
Increases quality of life
Decreases mortality
Gold standard treatment for end-stage renal disease
Decreases the cost to the health system
There are drugs with few side effects and effective in viral suppression of HIV
2. Cons
Increased risk of organ rejection
Increased risk of opportunistic infections
Greater need for tests to measure drug interactions
Need for scheduled biopsies to assess graft evolution
Will you elaborate more on HIVAN?
It is a serious manifestation resulting from the high viral load of HIV with significant glomerular damage, especially in the black population, with evolution to collapsing lesions.
There are also kidney injuries resulting from antiretroviral treatment, mainly with Tenofovir and protease inhibitors, but these can be removed and the scheme adapted to drugs that minimize kidney damage.
Proteinuria and metabolic control are essential, but the injury is often irreversible and transplantation is the only alternative for definitive treatment associated with strict viral load control and, consequently, maintaining higher serum CD4 levels.
What are the chances of recurrence of HIVAN post-transplantation?
Yes, there is a high risk, but there is a lack of robust data in the literature to quantify the true relative risk of this situation.
However, without a doubt, the best way to avoid its recurrence is strict viral load control, keeping HIV viral load levels below 50.
In Brazil, we measure the viral load twice a year or in case of clinical intercurrences or laboratory alterations. In special situations, such as a solid organ or bone marrow transplantation, we started measuring every four months.
Antiretroviral regimens with Dolutegravir, an integrase inhibitor, are considered the best, but depending on the sensitivity and clinical context in which the patient is inserted, other drugs may be used with the main objective of maintaining a negative viral load.
Virus genotyping, programmed biopsies, measurement of proteinuria, and serum dosage of immunosuppressants are our main weapons to keep the viral load undetectable.
Please counsel this patient in discussing the pros and cons of transplantation.
Kidney transplantation has been shown to remain the best form of renal replacement therapy, and with proper medical, surgical, and psychological workup, the outcome is usually good. Although CKD patients with HIV used to deny kidney transplantation, that is not the case again as many CKD patients living with HIV have gone through the procedure with a patient and graft survival of 88% and 74% after three years with the advent of use of HAART medications.
The following are the advantages of Kidney transplantation:
It offers better quality of life
It redues death attributable to CVD while on dialysis
There is increasing growing data on successful outcome of the procedure
Kidney transplantation is cheaper than dialysis after one year of transplantation
Availability of HAART mediations to help in suppression of viral load
Restoration of natural hormonal and metabolic functions of the kidney
The following are the disadvantages of Kidney transplantation:
Increase incidence of acute allograft rejection
increase rate of drug-drug interaction that could affect the immunosuppressive drugs or cause nephrotoxicity
increase incidence of malignancy
Elaborate more on HIVAN
HIVAN is the most severe form of CKD, and is the commonest cause of ESRD among those living with HIV. It is known to be very common among black population particularly those living in the West Africa (14.6%) where there has been an association with APOL1 gene mutation form past history of heavy burden of Trypanosomiasis. It is also the third commonest cause of ESRD globally. Although the discovery of HAART has significantly reduces the incidence, but compared to the general population, CKD among HIV patient is four times more
Histologically, it has a similar features to FSGS type of glomerular disease,but for the presence of tubular reticular inclusion within endothelia cell in the HIVAN
What are the chances of recurrence of HIVAN after transplantation
One study examined outcomes for 22 patients with HIV who had another transplantation, compared with over four thousand HIV-negative matched controls. The patients with HIV who had a second transplant had a 3.1-fold higher risk of death and a 1.96-fold increased risk of allograft loss, hence questioning the utility of the practice.
References
BTS.Kidney and Pancrease Transplantation in HIV with patient. Second Edition.
Thank you, isaac What are the other forms of HIVAN? You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Cocasian population.
Thank you, prof. for your response
I want to believe the other forms are:
non collapsing FSGS
Immune complex-mediated glomerulonephritis including, IgA nephropathy, MN, AND MPGN
Glomerulonephritis with co-infection with HCV and HBV
Yes, HIVAN has been reported in Caucasians, although rare compared to African-American with over 90% of cases
Reference
US Renal Data System, USRDS 2007 Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States, 2007Bethesda, MDNational Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
-HIV was traditionally considered an absolute contraindication for renal transplantation, but since the introduction of potent antiretroviral therapy (ART) became widely available , the prognosis of HIV patients was dramatically improved so HIV now is considered a a chronic manageable disease for many patients with well-controlled viral replication .
-Several studies have demonstrated comparable short- and intermediate -term patient and graft outcomes between HIV infected and non infected recipients after introduction of potent ART .
-In patients with HIV and ESKD , RTx has been associated with a survival benefit over dialysis but the risk of Acute rejection and infection was higher in the HIV population .
HIV associated nephropathy :
-HIV associated nephropathy , Collapsing variant of FSGS accompanied by microcystic tubular dilatation and interstitial inflammation
-It’s caused by direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host .
-It usually presents with heavy proteinuria and a rapid decline of renal functions with advanced HIV disease .
-Diagnosis is made through clinical suspicion in an HIV +ve patient witha CD4 <200 , HIV viremia or on no ttt .
-Treatments starts by start and adherence to ART , control of HTN and proteinuria (ACEI or , ARBs and SGLT2 may aid as well ) and management of metabolic disorders .
-Prognosis is poor
-There is risk of recurrence of HIVAN after Tx , of unknown rate yet of poor prognosis .
References :
1-Prof.Ahmed Halawa’s lecture
2-Up to date HIV and renal transplantation
Thank you, Dr Mohamed What are the other forms of HIVAN? Has it been reported in the Caucasian population? What about the recurrence after transplantation?
Pros:
Survival rate is better than hemodialysis.
1 and 3 years patient. And graft survival is similar to non HIv.
Cons:
There risk of recurrence of diseases.
Risk of opportunistic infection.
Risk of acute rejection.
Theoretical risk of more posttransplant malignancy.
HIV-associated nephropathy (HIVAN) is a renal parenchymal disease that occurs
exclusively in people living with HIV. It is a serious kidney condition that may possibly lead to end-stage kidney disease, particularly in the HIV-1 seropositive patient.
Risk of recurrence is remote and further studies on going to elaborate more evidence.
· Please counsel this patient discussing the pros and cons of transplantation.
Always transplant has been a better option then dialysis in ESRD patients.
To decrease the burden of dialysis and quality of life transplantation is a better option.
Proceeding for transplantation of HIV patient should be council for future recurrence of renal disease.
· Will you elaborate more on HIVAN?
HIVAN is the fate of HIV patients it not treated, its late consequence of the disease.
Usually these patient present with constitutional symptoms of recurrent infection, proteinuria, worsening renal function, and progressive renal failure.
Literature shows some association of genetic propenicity with HIVAN an apoliprotien (APOL1).
The most common presentation is GN with FSGS.
· What are the chances of recurrence of HIVAN post-transplantation?
Its significant concern of recurrence of disease.
To prevent the recurrence of disease, however, higher the viral load, there is higher risk of recurrence of disease.
The HIV copies should be less than 50 to proceed for transplantation,
CD4+T cell should be more then 200,
Treatment with HAART,
Pre-transplantation prophylactic, for PCP, CMV,
Vaccination for HBV, HAV, HZV, HPV, DPT, and MMR
Post-transplant annual vaccination,
Human immunodeficiency virus (HIV) infection has been associated with both acute kidney injury (AKI) and chronic kidney disease (CKD)
)HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS [1-3] although HIVAN may also occur in patients with less advanced HIV infection or following acute seroconversion [4,5]. Histologically, HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation [6].
Issues related to HIVAN will be discussed in this topic. An overview of kidney disease in people with HIV and discussions of electrolyte abnormalities, dialysis, and transplantation in people with HIV are provided elsewhere
https://www.uptodate.com/contents/hiv-associated-nephropathy-hivan#!
Please counsel this patient discussing the pros and cons of transplantation.
· Kidney transplantation is the best option for an ESRD patients including HIV-related recipients.
· HIV positive patients was not a common entity but this has changed in recent years with the use of the new HAART medications
· HIV + recipients should receive proper counseling about the pros and cons of renal transplantation compared to staying on dialysis.
Pros:
· Provides hope for HIV+ recipients who utilizes the currently available cART if they fulfill certain criteria
· Better patient survival and quality of life than remaining on dialysis.
· Utilizing HIV+ donors to HIV + recipients reduces the transplant waiting time
· Opportunistic infections that occur in the post-transplant period is not higher in HIV+ ve compared to HIV –ve recipients.
Cons:
· Increased rejection rates (2-3 times) including steroid-resistant rejection and delayed graft function compared to the general population.
· More drug interactions between cART and immunosuppressive agents
· Increased risk of malignancy associated with human papilloma virus, no increase in other malignancies
· Increased incidence of bacterial infections
· HIV AN recurrence after transplantation
Will you elaborate more on HIVAN?
· HIV-associated nephropathy (HIVAN) is the first kidney disease diagnosed in HIV-infected patients
· Risk factors:
o Race: 50 times more in African-Americans than in whites, with increased risk with presence of 2 APOL1 risk alleles
o proteinuria >3g per day and higher serum creatinine from baseline
o High viral load (>400 copies/ml) and CD4 count <200
· Clinical picture:
o Proteinuria (usually heavy up to nephrotic). However, edema and hypertension are not typically present.
o Rapid decline in renal functions to ESRD
· Diagnosis:
o Urine examination show a bland urinary sediments
o US shows enlarged swelling echogenic kidneys
o Biopsy is required to differentiate from other cause and show collapsing FSGS, interstitial nephritis, visceral epithelial cell proliferation, endothelial tubuloreticular inclusions, and tubular microcystic dilatation. The Tubulo-interstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease.
· Management:
o Initiation of cART (regardless of CD4 count),
o Control of proteinuria with ACE inhibitors or ARBs
o Steroids to reduce tubule-interstitial inflammation
o If ESRD developed, renal replacement therapy in form of dialysis and transplant( offered to patient who fulfills certain criteria) is available.
What are the chances of recurrence of HIVAN post-transplantation?
· Chances increase if the donor is HIV-positive. However, there is no correlation between the recurrence of HIVAN and viral loads.
· The chances for recurrence depends on the adequacy of the treatment of HIV with cART. So, if managed well keeping in mind the interaction with transplant immunosuppression. The chances will be low.
· The location of the viral reservoir in the transplanted kidney is important as graft function deteriorate if the virus is identified in the podocytes and not in the tubular cell of the transplanted kidney.
References:
1. Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11.
2. Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501.
3. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116.
4. British Transplantation Society. Kidney and Pancreas Transplantation in patients with HIV, 2nd ed.; British Transplantation Society: Macclesfield, UK, 2017
HIV positive patients had been successfully transplanted for the last 15 years and the donor pool had successfully been expanded to also include HIV positive donors.
HIV positive patients should be selected for transplantation according to standard selection criteria, similar to HIV negative transplant recipients. Additional recommendations, specific to HIV, include:
-patient should be virally suppressed (undetectable viral load) and be on a stable ART regimen for at least 3 months before the date of the transplant.
-patients must have a CD4 count above 200 cells/mm3, but patients with lower CD4 counts.
Pros:
– improved quality of life and better long-term prognosis and survival.
-Opportunistic infections encountered post-transplant in HIV-positive patients are not significantly higher than HIV-negative recipients .
Cons
– rejection rates and DGF are higher than in the general population .
-Increased incidence of bacterial infections
Only patients with fully treated tuberculosis should be considered for transplantation.
-drug-drug interactions between cART and immunosuppressive agents .
superior outcomes had been reported with integrase strand transfer inhibitor-based antiretroviral regimens, as there is no interaction with calcineurin inhibitors but if this no available the PIs have been used to decrease the amount of CNI that the HIV positive recipients require, hence saving drug costs .
– Patients with opportunistic infections and neoplasms without effective medical therapy are generally excluded (PML, chronic intestinal cryptosporidiosis).
–ATG has been shown to be associated with decreased patient and graft survival and it is better to use basileximab
-In the case of using HIV positive deceased donors, particular attention should be given to the risk of donor derived infections like latent tuberculosis and strongyloidiasis in endemic areas.
Screening for sexually transmitted diseases such as syphilis, West Nile Virus and Chagas parasitic disease are important.
–De novo HHV8- mediated Kaposi’s sarcoma (KS) had been reported in some HIV infected transplant recipients, but switching immunosuppressive regimens to include TOR inhibitors generally controlled this.
– Chronic immune activation and inflammation is known to contribute to the risk of cardiovascular diseases in HIV positive patients.
Pathologically HIVAN is defined by:
-a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy.
-Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features.
-In ART-treated patients, a non-collapsing form of FSGS called FSGS (NOS) is more commonly encountered at biopsy.
-Numerous forms of immune complex-mediated glomerular disease have been reported in HIV-positive individuals.
-These immune complex-mediated glomerular diseases can include multiple patterns: mesangial proliferative, membranous, membranoproliferative, endocapillary proliferative, and crescentic forms.
Clinically presents with nephrotic syndrome, rapid progression ESRD, and irreversible renal failure .
The risk of recurrence post-transplant is highe if the donor is HIV-infected.
The risk of recurrence is low if HIV infection is well controlled by medication
References:
Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1; 105(7): 1492–1501.
Will you elaborate more on HIVAN?
Specific infection screening considerations in HIV positive TX
HPV screening post transplantation:
Prophylactic therapy:
Vaccinations post-transplant:
Immunosuppression & antiretroviral therapy challenges
What are the chances of recurrence of HIVAN post-transplantation?
Please counsel this patient in discussing the pros and cons of transplantation.
Advantages (pro) kidney transplantation
Disadvantages
Will you elaborate more on HIVAN?
Classically manifested by focal segmental glomerulosclerosis (collapsing). Patient with HIVAN will experience proteinuria and rapidly worsening renal function. Anti-retroviral therapy is the mainstay of therapy (1).
What are the chances of recurrence of HIVAN post-transplantation?
Recurrence post-transplant is low but compared to non-HIV individual there are at higher rate of acute rejection (2).
Reference
Q1:
Pros:
good survival for graft and patient, especially in compared with remaining on waiting list. In addition, the quality of life would be better, too.
Cons:
The higher rate of infection, malignancy, DGF, rejection and drug interactions.
Q2:
HIV-associated nephropathy (HIVAN) starts with proteinuria and could proceed to ESKD. Risk factors are high viral load, low CD4, APOL1 mutations (especially in blacks), but have been reported in Caucasians, too.
Glomerular nephropathy: are usually developed by immune complex.
Tubulointerstitial nephropathy: is related to the treatment of HIV by drugs and opportunistic infections.
Vascular NP: TMA and atherosclerosis or age-dependent nephrosclerosis.
Treatment includes effective HIV treatment and starting ACEi or ARBs or even steroids if needed.
Q3: In one study from the Paris, no recurrence of HIVAN after kidney transplantation, among 27 recipients was noted.
Reference:
1.Blumberg, E. A., & Rogers, C. C. (2019). Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation, 33(9). https://doi.org/10.1111/ctr.13499
2.Touzot, M., Pillebout, E., Matignon, M., Tricot, L., Viard, J. P., Rondeau, E., Legendre, C., Glotz, D., Delahousse, M., Lang, P., & Peraldi, M. N. (2010). Renal transplantation in HIV-infected patients: The Paris experience. American Journal of Transplantation, 10(10). https://doi.org/10.1111/j.1600-6143.2010.03258.x
HIV infection is not contraindications for renal transplantation .
discussing the pros and cons of transplantation.
Kidney patient due to hiv infection have better survival with transplantation,better life by getting of hemodialysis,however have more complication compare to non hiv patients due to the use of strong immunosuppressi agent which may activate the virus ore make it stronger .
No.
The chance of recurrence is low.
The patient is a known case of CKD…he is HIV positive…He needs live related renal transplant…Even in those individuals with HIV there is a survival advantage of those who are on dialysis…There is overall mortality benefit for those after transplant as compared to dialysis and HIV…..
The pros are cART availability has made it possible for transplantation as a viable treatment option for HIV positive patient….They need to fulfill few criteria before transplant like absence of HIV resistance, absence of few oppurtunistic infections like PML, cyrptosporidiosis, no active TB, CD4 count>200 for 6 months, negative HIV RNA viral load for 3 months… There is definitive survival advantage after transplant in HIV individuals..There are studies to show that oppurtunistic infections encountered post transplant in HIV positive patients are not higher than HIV negative individuals….Even on cadaver list the waiting time of HIV positive recipient
The patients who have developed HIVAN and are on dialysis have few points of concern before transplantation…There has been increased reports on rejection and delayed graft function in the population….There is a concern of increased risk of oppurtunistic infection and malignancy in HIV individuals and IL2 receptor antagonists are better choice as compared to the ATG…Older HIV individuals with diabetes are known to have poor graft function as compared to younger HIV individuals….There is also increased drug interaction reported with cART and immunosuppressive agents…
Elaboration on HIVAN:
HIV associated nephropathy is the first kidney disease diagnosed in patients with HIV infected patients….The original description is of nephrotic syndrome having collapsing type of FSGS which leads to CKD and dialysis… HIVAN is more common (50-60 times) in African American individuals..The incidence is more common in individuals with HIV viral load >400 copies/ml, proteinuria > 3 gm/day, CD4 count <200 cells/cumm. The risk of HIVAN is more in individuals with APOL 1 gene with 2 allele….They will present with azotaemia…They will not usually have edema and hypertension….Patients with HIVAN will progress rapidly to CKD and ESRD…urine routine will show nephrotic range proteinuria and hematuria….Kidney biopsy shows collapsing FSGS..Other biopsy features reported with HIV are interstitial nephritis, pseudocrescents, endothelial tubulo reticular interactions and tubular microcystic dilatation….Steroids are used to control the proteinuria and interstitial inflammation….
There is no correlation between the HIV Viral load and recurrence of HIVAN after renal transplant….There are reports of recurrence of HIVAN if the donor has high viral load and not adequately treated before a live or cadaver transplant…Collapsing FSGS has shown to have a high recurrence if the virus is housed in the podocyte..Other forms of HIVAN like proliferative GN and Chronic interstitial nephritis are not known to recur…If the HIV is well managed with cART the chances of recurrence are low…The bottomline is good HAART therapy will keep the viral load under control and reduce the recurrence..HIVAN recurrence has not been reported in US clinical trials
PROS
– Increased life span perspective
– Leaving hemodialysis
CONS
– Risk of transplant-related complications: opportunistic infections
– increase in the number of medications – polypharmacy
Clinically, it presents with progressive azotemia, significant proteinuria and little or no peripheral edema in patients with advanced HIV disease. Renal parenchymal injury is characterized by epithelial cell proliferation, dedifferentiation and apoptosis along the entire nephron. Histologically, it is distinguished by finding collapsing glomerulopathy, microcystic tubular dilation, interstitial inflammation and fibrosis.
African studies indicate that this risk is low.
REFERENCE:
Gilbert J, Manji A. Considerations in the Management of a Kidney Transplant Patient With HIV. Cureus. 2021 Oct 13;13(10):e18744. doi: 10.7759/cureus.18744. PMID: 34659933; PMCID: PMC8513352.
Botha J, Fabian J, Etheredge H, Conradie F, Tiemessen CT. HIV and Solid Organ Transplantation: Where Are we Now. Curr HIV/AIDS Rep. 2019 Oct;16(5):404-413. doi: 10.1007/s11904-019-00460-7. PMID: 31482298; PMCID: PMC6813753.
Medapalli RK, He JC, Klotman PE. HIV-associated nephropathy: pathogenesis. Curr Opin Nephrol Hypertens. 2011 May;20(3):306-11. doi: 10.1097/MNH.0b013e328345359a. PMID: 21358326; PMCID: PMC3153858.
1. Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplant even for HIV+ recipients, offers
· Better quality of life and Survival benefit compared to HD
· But risk of DGF, rejection is increased, as is isk of opportunistic infection and malignancy.
HIV-associated nephropathy (HIVAN)
· is the most severe form of CKD; commonest cause of ESRD in HIV-positive patients in the UK
· Patients are typically young (mean 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure.
The majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
· Kidney transplantation in HIV-positive patients is complicated by a high rate of acute allograft rejection
· Immunosuppression has been well tolerated and HIV viraemia uncommon, although renal complications are relatively frequent. Few patients experience opportunistic infections, HIV disease progression or malignancy.
· Most studies suggest that kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise fit and eligible, with life expectancy >5 years.
· HAART / cART has improved survival in patients with HIVAN in addition to decreasing the incidence of HIVAN in PLHIV and reducing the risk for progression to RRT
· Currently it is recommended to initiate cART in patients with HIVAN, regardless of CD4 cell count
· Graft rejection is also a major concern in this population, due to immune dysregulation and the drug interactions between ART and CNI
· Counselling the patient about the disease and need for taking HARTT to keep HIV controlled (viral load <50 copies /ml or undetectable).
· The patient needs to know that HIVAN could recur in the transplanted kidney.
2. Will you elaborate more on HIVAN?
It causes glomerular disease with collapsing FSGN and nephrotic syndrome with heavy proteinuria.
The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function, even in the absence of oedema.
Biopsy with E/M shows subendothelial tubule-reticualr inclusion bodies, not 100% specific / sensitive.
The prognosis in patients with HIVAN is poor, even among those treated with antiretroviral therapy
More common in African population.
In studies of adult and pediatric people with HIV, 96-100% were African descent.
According to data from the (USRDS), more than 85 % of new (ESKD) cases attributed to HIVAN occur in African Americans.
In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
Study compared patients with non-HIVAN ESKD and patients with HIVAN ESKD found that the latter had increased mortality
Proper donor selection – rule out proteinuria, may need biopsy.
What are the chances of recurrence of HIVAN post-transplantation?
There is a risk of HIVAN recurrence in the graft post-transplantation, particularly in cases wherein the donor is HIV positive
Reported in 23.5% of cases with 3% graft loss according to south African study.
References:
1. HIV-Associated Nephropathy in 2022
2. British Transplantation Society Guidelines
3. Winston JA et al; Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344;1979
4. Up to date
HIVAN
IT IS cause glomerular disease with collapsing FSGN and nephrotic syndrom with heavy proteinura . which is more more common in african population . biopsy showed E/M it presents with subendothelial tubuloreticualr inclusion bodies.
This condition need counseling the patient about the disease ,and if the patient want to do kidney transplant he has to take the HARTT first and keep HIV PCR COPIES BELOW 50, ADDING TO THAT , proper donor selection ,he has to know that RTX survival is better than to remain odn dialysis.
The patient need to know that HIVAN could recur in the transplanted kidney.
references
uptodate
Pros:
Better quality of life
Survival benefit compared to HD
Cons:
Increased risk of DGF
Increased risk of opportunistic infection and malignancy
Increased risk of rejection
Will you elaborate more on HIVAN?
HIVAN is classic renal manifestation of HIV but incidence had decreased due to HAART. Patients usually have low CD4 count and increased viral load. Patients have nephrotic syndrome with rapid rise of serum creatinine and histopathology shows collapsing variant of FSGS. Predominantly affects patients of African ancestry due to APOL1 risk alleles. HAART slows the progression.
Recurrence:
HIVAN is a secondary form of FSGS, if HIV infection is managed well with cART, the chances of recurrence are low.
Please counsel this patient discussing the pros and cons of transplantation.
· HIV-associated nephropathy (HIVAN) is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK
· Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure.
· The majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
· Kidney transplantation in HIV-positive patients is complicated by a high rate of acute allograft rejection
· Immunosuppression appears to be well tolerated, with few patients experiencing opportunistic infections, HIV disease progression or malignancy.
· Immunosuppression has been well tolerated and HIV viraemia uncommon, although renal complications are relatively frequent
· Most studies suggest that kidney transplantation should be offered to HIV-positive patients with ESRD who are otherwise eligible.
· cART has dramatically improved survival in patients with HIVAN in addition to decreasing the incidence of HIVAN in PLHIV and reducing the risk for progression to RRT
· Currently it is recommended to initiate cART in patients with HIVAN, regardless of CD4 cell count
· Graft rejection is also a major concern in this population, given the baseline immune dysregulation and the drug interactions between cART and calcineurin inhibitors
Will you elaborate more on HIVAN?
· The prognosis in patients with HIVAN is poor, even among those treated with antiretroviral therapy
· The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function, even in the absence of edema.
· HIVAN displays a striking racial predilection for individuals of African descent. In studies of adult and pediatric people with HIV, 96 to 100 percent were of African descent.
· According to data from the (USRDS), more than 85 % of new (ESKD) cases attributed to HIVAN occur in African Americans.
· In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
· A study compared patients with non-HIVAN ESKD and patients with HIVAN ESKD found that the latter had increased mortality
What are the chances of recurrence of HIVAN post-transplantation?
· There is a risk of HIVAN recurrence in the graft post-transplantation, particularly in cases wherein the donor is HIV positive
1) HIV-Associated Nephropathy in 2022
2) British Transplantation Society Guidelines
3) https://www.uptodate.com/contents/hiv-associated-nephropathy-hivan?search=HIVAN&source=search_result&selectedTitle=1~25&usage_type=default&display_rank=1#H4239415236:~:text=Back-,HIV%2Dassociated%20nephropathy%20(HIVAN),-Topic
Kidney transplant is a valid choice in HIVAN WITH ESRD
ADVANCTAGES
better than dialysis
effective CART make organ transplant possible in HIV
DISADVANTAGES
increase risk of acute and delayed rejection
Increase risk of drug drug interactions
Increase risk of infections
Increase risk of malignancy
HIVAN – it a type of collapsing FSGN with nephrotic grade proteinuria , normal size echogenic kidney on USG seen in HIV patients with characteristic biopsy findings like microcyst
HIVAN can recur post kidney transplantation
in African American population
The patient should know the following recommendations of British Transplantation Society Guidelines kidney and pancreas transplantation in patients with HIV
All potential kidney transplant recipients are screened for HIV infection
• HIV per se is not a contraindication for kidney transplantation
• HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/µL (ideally > 200 cells/ µL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
The most appropriate anti-retroviral therapy is determined before transplantation in conjunction with an HIV specialist in order to anticipate potential drug interactions and appropriate dosing of medication.
Pros
Cons
HIV-associated nephropathy (HIVAN) is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK (7). Patients of black ethnicity, who constitute one third of those diagnosed with HIV in the UK, are at increased risk of ESRD (7,9,10). Patients with HIVAN are typically young (mean age 36 years) with severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median estimated glomerular filtration rate [eGFR] 21 mL/min/1.73m2 ) at diagnosis (11). Although suppression of HIV replication may improve or stabilise kidney function, the majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
The podocytopathy can manifest as focal segmental glomerulosclerosis (FSGS) or minimal change disease and diffuse mesangial hypercellularity
Classic HIVAN, as originally described in the pre-ART era continues to occur among ART-naïve or non-adherent patients, usually of African descent, irrespective of the mode of HIV transmission. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV positive patients. Diagnosis is confirmed by a nephrotic range proteinuria, and increased renal echogenicity on ultrasound and a kidney biopsy.28
Pathologically HIVAN is defined by a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy.Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features.
Tubulointerstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease. It accounts for marked kidney enlargement and hyperechoic appearance by ultrasound. Typical tubulointerstitial features include tubular microcysts,” which are dilated tubules (at least 3-fold the diameter of normal tubules) containing glassy proteinaceous casts lined by flattened, simplified epithelium. The microcysts may be focal or diffuse and may involve cortex and medulla, including proximal, distal and collecting tubular segments.
HIVAN recurrence is a concern in some HIV positive transplant programs. In the South African group features of HIVAN presented many years after the transplant and had a slow progression having no clinical impact in most cases.
HIV patients without VL and no CI can be considered for transplantation.
Pros.
Cons.
-HIVAN:
. Collapsing FSGS with tubular dilatation and interstitial inflammation. HIVAN entails HIV infecting epithelial cells and expression of HIV gene in susceptible patients. Genetics is important in etiopathogenesis as proved by increased incidences in APOL1 gene polymorphisms and in Africans.
Recurrence of HIVAN
Winston JA et al; Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344;1979
HIVAN
IT IS cause glomerular disease with collapsing FSGN and nephrotic syndrom with heavy proteinura . which is more more common in african population . biopsy showed E/M it presents with subendothelial tubuloreticualr inclusion bodies.
This condition need counseling the patient about the disease ,and if the patient want to do kidney transplant he has to take the HARTT first and keep HIV PCR COPIES BELOW 50, ADDING TO THAT , proper donor selection ,he has to know that RTX survival is better than to remain odn dialysis.
The patient need to know that HIVAN could recur in the transplanted kidney.
references
uptodate
1- Counselling:
2- HIVAN:
3- Recurrence: is expected if viral load is not controlled.
5. A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
– HIV positive patients are more susceptible to kidney disease than their HIV negative counterparts so kidney transplantation does not entirely absolve them from kidney issues
– this is due to the direct impact of the HIV virus on the kidney as well as the associated immune response
Pros of kidney transplantation
– kidney transplantation is the best treatment modality for ESKD patients
– no need for dialysis
– better quality of life
– shorter waiting time
Cons of kidney transplantation
– major surgery with potential risk
– risk of infections and malignancies following kidney transplant
– risk of delayed graft function
– risk of rejection
– lifelong immunosuppressive drugs
– drug-drug interactions between HAART and the immunosuppressive drugs
– risk of HIVAN recurrence in the graft kidney
Will you elaborate more on HIVAN?
– HIVAN is described as the classic kidney disease commonly associated with HIV infection (1)
– histologically, it is a collapsing form of FSGS accompanied by microcystic tubular dilatation and interstitial inflammation (2)
– Pathogenesis: HIV directly infects glomerular and kidney tubular epithelial cells with subsequent expression of HIV genes within the infected kidney cells in a genetically susceptible host (3)
– Risk factors: African ancestry, APOL1 gene polymorphisms, HAART naïve, poor adherence (4, 5)
– Clinical manifestations: (6)
– Diagnosis: (7)
– Differential diagnosis: noncollapsing FSGS, immune complex-mediated GN (IgA, MN, MPGN, lupus-like proliferative GN), GN due to HBV or HCV co-infection, DKD, amyloidosis (7)
– Treatment – no RCTs have been done to evaluate the therapies listed below:
– Prognosis: remains poor even among those on HAART, many
such patients progress to ESKD
What are the chances of recurrence of HIVAN post-transplantation?
– HIVAN recurrence is a major concern, requires more attention in the future
References
1. Gardenswartz MH, Lerner CW, Seligson GR, Zabetakis PM, Rotterdam H, Tapper ML, et al. Renal disease in patients with AIDS: a clinicopathologic study. Clinical nephrology. 1984 Apr;21(4):197-204. PubMed PMID: 6733986. Epub 1984/04/01. eng.
2. Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int. 1999 Dec;56(6):2203-13. PubMed PMID: 10594796. Epub 1999/12/14. eng.
3. Bruggeman LA, Ross MD, Tanji N, Cara A, Dikman S, Gordon RE, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. Journal of the American Society of Nephrology : JASN. 2000 Nov;11(11):2079-87. PubMed PMID: 11053484. Epub 2000/10/29. eng.
4. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. Journal of the American Society of Nephrology : JASN. 2011 Nov;22(11):2129-37. PubMed PMID: 21997394. Pubmed Central PMCID: PMC3231787. Epub 2011/10/15. eng.
5. Kudose S, Santoriello D, Bomback AS, Stokes MB, Batal I, Markowitz GS, et al. The spectrum of kidney biopsy findings in HIV-infected patients in the modern era. Kidney Int. 2020 May;97(5):1006-16. PubMed PMID: 32278618. Epub 2020/04/13. eng.
6. Bigé N, Lanternier F, Viard JP, Kamgang P, Daugas E, Elie C, et al. Presentation of HIV-associated nephropathy and outcome in HAART-treated patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2012 Mar;27(3):1114-21. PubMed PMID: 21745806. Epub 2011/07/13. eng.
7. Atta MG, Choi MJ, Longenecker JC, Haymart M, Wu J, Nagajothi N, et al. Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. The American journal of medicine. 2005 Nov;118(11):1288. PubMed PMID: 16271919. Epub 2005/11/08. eng.
8. Eustace JA, Nuermberger E, Choi M, Scheel PJ, Jr., Moore R, Briggs WA. Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids. Kidney Int. 2000 Sep;58(3):1253-60. PubMed PMID: 10972688. Epub 2000/09/06. eng.
Pros of transplantation in a patient on dialysis include:
· Better quality of life and patient survival
· Risk of HIV viremia is low if the patient fulfilling specific criteria and well controlled on HAART
· Risk of HIVAN post transplant is low if viremia controlled on HAART.
· Rate of opportunistic infection not significantly higher than non HIV recipient
Cons of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
· Higher rate of rejection
· Some immunosuppresions have greater risk of HIV activation and better to be avoided
· Some HAART medications interact with immunosuppresions and to be modified.
· Maliganacy is higher especially with human papilloma virus
Its 2ry FSGS related to HIV.multicenter study done is US showed low rate of recurrence post transplant if the patient fullfiling specific criteria pretransplant with good compliance on cART post transplant.
References:
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
-HIV pts with undetectable VL and no other CI to transplant should all be considered for renal transplantation. The HOPE treaty allows HIV pts to enroll as donors.
Pros;
Cons;
Will you elaborate more on HIVAN?
HIVAN Recurrence;
-A south African study involving 51 KTR had 23.5% of pts with recurrence of nephropathy and 3% graft loss. All those with nephropathy had suppressed VL during the study.
REF;
Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplantation is the best treatment option for the eligible patient with ESRD regardless of their HIV status.
Pros
It is associated with better quality of life and survival rates than being on dialysis.
It is more cost effective than dialysis.
Cons
There are strict criteria that one has to fulfil to make you eligible.
There is increased risk of infections and malignancy hence need of prophylaxis medications that may increase ones pill burden.
There is an increased risk of rejection this could be due to drug interactions between the ART and immunosuppressive medication.
There is a higher rate of DGF in the HIV population hence one might be on dialysis briefly after transplantation.
Will you elaborate more on HIVAN?
HIVAN is the classic kidney disease of HIV infection however its incidence has been declining with the use of cART.
It presents usually in the patient with a low CD4 counts and high viral loads with heavy proteinuria, rapidly rising Scr and histopathological findings of collapsing glomerulosclerosis and tubulointerstial inflammation.
It predominantly affects persons of African ancestry due to the predominance of the APOL1 risk alleles.
Use of cART can prevent it and reverse it.
Treatment involves initiation of cART in the ART naive patient, blockade of the RAAS, steroids and RRT
What are the chances of recurrence of HIVAN post-transplantation?
A south African study where 51 patients were followed up for 10 year period, 12 patients had features of HIVAN on per protocol biopsy with only 2 of them who lost their graft.
Further research is thus required.
References
HIV-Associated Nephropathy in 2022
Rivera F.B.a, Ansay M.F.M.b, Golbin J.M.c, Alfonso P.G.I.c, Mangubat G.F.E.d , Menghrajani R.H.S.e, Placino S.e,Taliño M.K.V.b, De Luna D.V.f, Cabrera N.g, Trinidad C.N.h, Kazory A.i
HIV-associated nephropathy: links, risks and management
Laura Palau, Steven Menez, […], and Mohamed G Atta
Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies
Elmi Muller, MD PhD, Francois C. J. Botha, MBChB, […], and Peter Stock, MD PhD
Kidney transplantation is the best RRT option, irrespective of the HIV status of the recipient.
The pros of transplantation include:
1. better survival rates.
2. better quality of life.
3. Because of the availability of cART, transplantation is now a viable treatment option for HIV-positive patients who meet certain criteria.
4.waiting time on the waitlist may be reduced by the option of HIV-positive donor acceptance.
Kidney transplantation is the best RRT option, irrespective HIV status of the recipient.
The cons of transplantation include:
1- increased rates of rejection & DGF if compared to the general population.
2- drug interactions should be considered & monitored closely.
3- increased risk of infection & malignancy post-transplantation
4-incidence of HPV-mediated cancers
5- the risk of HIVAN recurrence was reported
HIV-associated nephropathy (HIVAN)can present by nephrotic syndrome (with a collapsing FSGS), rapid progression to ESRD.
– HIVAN risk is 50 times higher in African-Americans than in whites, and the existence of 2 APOL1 risk alleles increases the risk.
-clinical picture:
1- CD4 count of 200, a high viral load (>400 copies/ml).
2- proteinuria, Edema and hypertension .
3- high s.creatinie
4- renal biopsy: characterized by FSGS collapse, interstitial nephritis, visceral epithelial cell proliferation.Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features.
-management:
1- cART (independent of CD4 count).
2-anti proteinuric measures ( low salt diet, bl.p control, ACEI or ARBS , diuretics)
3-CKD management, with RRT options with priority of transplanatation
-HIVAN recurrence is concern.
conclosions from Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies
Muller, Elmi MD, PhD1; Botha, Francois C. J. MBChB2; Barday, Zunaid A. MBChB3; Manning, Kathryn MPH1; Chin-Hong, Peter MD, PhD4; Stock, Peter MD, PhD5
-HIVAN symptoms appeared many years after the transplant in the South African group and progressed slowly without clinical significance. In the 51 South African transplants, 12 patients had HIVAN-related biopsy abnormalities, although only 2 lost their grafts. These patients experienced rejection in the first three years following transplantation.
-All HIVAN recurrence patients had undetectable viral levels throughout the investigation. This study observed no link between donor viral load and HIVAN recurrence.
-HIVAN occurred in 2 of 150 HIV-positive individuals in a US multicenter trial.
-HIVAN recurrence must be addressed in the future.
-Canaud et al.47 report rapid graft function decline after HIVAN diagnosis in the podocyte rather than the tubular cell of the transplanted kidney. Canaud et al. found a significant rate of HIV infection in transplanted kidneys, but the US trial did not (source NEJM). Future research will investigate these discrepancies.
– Aggressive immunosuppression to treat rejection may cause a kidney viral reservoir flare-up.
Please counsel this patient discussing the pros and cons of transplantation.
Pros of transplantation include:
Cons of transplantation include:
Will you elaborate more on HIVAN?
Clinical Features: HIV-infected patients may present at any age with HIVAN, which is a collapsing form of FSGS. Usual findings are nephrotic syndrome, progressively increasing serum creatinine at presentation, and rapid progression, with about half reaching ESRD within 3 years. Edema and hypertension are not typically seen in HIVAN. Patients will have high viral load and low CD4 counts signifying advanced HIV infection. Kidneys are often enlarged in HIVAN patients on ultrasound. A kidney biopsy in needed for confirmatory diagnosis.
Light microscopy: Segmental or global glomerular tuft collapse with overlying visceral epithelial hyperplasia and hypertrophy is seen. Hypertrophied visceral epithelial cells have frequent protein droplets. There is accompanying microcystic tubular dilatation and active tubulointerstitial nephritis with a predominantly lymphocytic infiltrate, often with tubulitis and edema.
Immunofluorescence microscopy: No or limited immune deposits (nonspecific IgM and C3 staining in collapsed segments) are identified. .
Electron microscopy: Glomerular basement membranes are wrinkled and collapsed. Overlying visceral epithelial cells show hypertrophy and hyperplasia, with frequent vacuoles and protein droplets. There is extensive foot process effacement and no or limited mesangial deposits. Tubuloreticular aggregates are present in endothelial cells.
The prevalence of HIVAN among HIV-infected individuals has decreased dramatically since the advent of combination antiretroviral therapy (cART).
Differential Diagnosis: Collapsing glomerulopathy can be related to other infections (eg, parvovirus), drugs (eg, bisphosphonates and calcineurin inhibitors), thrombotic microangiopathy or systemic lupus erythematosus.
History of HIV infection and the presence of tubuloreticular aggregates indicate HIVAN as the etiology of the collapsing lesions.
Management: Initiation of cART , ACE inhibitors or ARBs, and steroids (to reduce tubulointerstitial inflammation). Dialysis is initiated in case ESRD develops and transplantation is an option. Renal transplant should be offered if the patient fulfils certain criteria like CD4 count >200 and undetectable viral load by PCR.
What are the chances of recurrence of HIVAN post-transplantation?
In a study 64% patients developed delayed graft function (DGF), and 54% patients required post-operative dialysis within one week of transplant. Graft survival rates at 1 and 3 years were 100% and 81%, respectively. Acute rejection rates at 1 and 3 years were 18% and 27%, respectively. If HIV infection is managed well with cART, the chances of recurrence are low.
References:
Above data for the short-term outcome, but data regarding long-term outcomes and comparisons with appropriately matched HIV− patients are
still lacking.
These outcomes are inferior to other transplant recipients without HIV but better than dialysis patients.
Other disadvantages of kidney transplantation in HIV +ve patients is interaction between HAARTs and some immunosuppressive medications. Which means that we need special concentration on these drugs, measure the level whenever available,
HIV infection can directly cause renal dysfunction in a variety of ways, including HIV-associated nephropathy (HIVAN), immune complex diseases, and thrombotic microangiopathy. HIVAN occurs in approximately 10% of patients with HIV and is the third most common etiology of end-stage renal disease (ESRD) among African Americans aged 20–64 years.
HIVAN is pathologically characterized by a collapsing glomerulopathy with active tubulointerstitial inflammation.
In South African study it occurred in 12 out of 51 cases. However, only 2 cases lost their graft as result of the recurrence.
In American cohort the recurrence was much less in 2 out of 150 cases over 3years.
References;
1-HIV-associated nephropathy: links, risks
and managementHIV/AIDS – Research and Palliative Care 2018:10 73–81.
2-Kidney transplant outcomes in HIV‑positive patients: a systematic review and meta‑analysis, Zheng et al. AIDS Res Ther (2019) 16:37
3- Challenges of kidney transplantation in HIV positive recipients
Mahmoud Alameddine1, Joshua S. Jue2, Ian Zheng1, Gaetano Ciancio1 Transl Androl Urol 2019;8(2):148-154
Counseling
Pros of kidney transplant
Cons of kidney transplant
HIVAN
Chances of recurrence of HIVAN post transplantation
References
HIVAN recurrence is found to not have much data at present. There is however evidence suggesting that immune complex mediated GN is a significant contributor to kidney disease in the HIV population. Clinical and histological recurrence of HIV associated lupus like nephritis after successful kidney transplantation is rare and causes hematuria, proteinuria and impaired kidney function.
Further studies are needed to accurately assess the rates of HIVAN recurrence after kidney transplant.
Reference
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013 Aug;62(2):335-8. doi: 10.1053/j.ajkd.2013.01.010. Epub 2013 Mar 5. PMID: 23481367; PMCID: PMC4121438.
Please counsel this patient discussing the pros and cons of transplantation.
HIV per se is not a contraindication for kidney transplantation. HIV positive patients should be selected for transplantation according to standard selection criteria, similar to HIV negative transplant recipients. Additional recommendations, include that the patient should be virally suppressed (undetectable viral load) and be on a stable ART regimen for at least 3 months before the date of the transplant. Ideally the patients must have a CD4 count above 200 cells/mm3, but patients with lower CD4 counts have been transplanted successfully in the past.
The transplantation of recipients with low, but detectable levels of HIV remains a contentious issue. Some programs are moving forward with transplantation in this cohort. The majority of clinicians will accept patients for transplantation with a temporary viral load increase that is less than 200cps/ml. Nonetheless, since this may represent low grade replication, transplantation of HIV positive recipients with viral loads less the 200 cps/ml should be limited to centres with a broad experience in the transplantation and management of the HIV infected recipient.
HIV-Associated Nephropathy (HIVAN) is most prevalent in patients who receive antiretroviral therapy (ART) late after initial diagnosis, and is a major cause for CKD.
High rates of infection-related nephropathies and a limited capacity for secondary prevention result in more rapid progression to organ failure . Estimating the burden of CKD in HIV-positive patients is important when considering the allocation of resources including dialysis, availability of deceased and living donor organs, and transplantation.
To know the benefits of transplantation in the HIV infected population.
To know underlying burden of organ failure and its risk factors, irrespective of current treatment availability or eligibility criteria.
Also the improved quality of life and better long-term prognosis of a HIV positive patient, the focus for treatment for these patients have moved to transplantation rather than dialysis over the last 10 years.
Will you elaborate more on HIVAN?
HIV-positive individuals is diverse, including lesions directly related to intrarenal HIV gene expression and lesions related to co-morbidities, drug effects, immune dysregulation, and other co-infections . Podocytopathy or immune complex-mediated glomerular disease are two common manifestations of HIV in the kidney.
The podocytopathy can manifest as focal segmental glomerulosclerosis (FSGS) or minimal change disease and diffuse mesangial hypercellularity.
Because of the direct impact of the virus on the kidney as well as the associated immune response, HIV positive patients are more suspectable to CKD than HIV negative patients..
What are the chances of recurrence of HIVAN post-transplantation?
Yes there are chances of HIVAN recurrance, but data is lacking and needs more studies
References
1. Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clinical nephrology. 2015;83(7 Suppl 1):32–8. [PMC free article] [PubMed] [Google Scholar]
2. Cohen SD, Kopp JB, Kimmel PL. Kidney diseases associated with human immunodeficiency virus infection. N Engl J Med. 2017;377(24):2363–2374. Doi: 10.1056/NEJMra1508467 [PubMed] [CrossRef] [Google Scholar]
3. Ma L, Divers J, Freedman BI. Mechanisms of injury in APOL1-associated kidney disease. Transplantation. 2019;103(3):487–492. Doi: 10.1097/TP.0000000000002509 [PMC free article] [PubMed] [CrossRef] [Google Scholar]
4. Harbell J, Terrault NA, Stock P. Solid organ transplants in HIV-infected patients. Current HIV/AIDS reports. 2013;10(3):217–25. Doi: 10.1007/s11904-013-0170-z [PMC free article] [PubMed] [CrossRef] [Google Scholar
5. . Roland ME, Barin B, Huprikar S, et al. Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls. AIDS. 2016;30(3):435–44. Doi: 10.1097/QAD.0000000000000934 [PMC free article] [PubMed] [CrossRef] [Google Scholar
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
HIV per se is not a contraindication for kidney transplantation.
End stage renal disease 2/2 HIV should be offered transplant if there CD4.
count is more than 200 cells/microliter for at least 3 months and the viral
load is undetectable for the same period and the patient has.
demonstrated compliance and has no active infection and/or malignancy.
HIV-positive patients are wait-listed only if:
a) They are adherence with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
Please counsel this patient discussing the pros and cons of transplantation.
Pre-transplant testing and immunization, immunosuppressive protocol, post-transplant prophylaxis, risk of rejection, prognosis, long-term results, post-transplantation problems, HIV infection, and delayed graft function.
Kidney Tx. can be successful in HIV+ patients, but further studies are needed to optimize immunosuppressive therapy regimens to reduce AR after transplantation.
Kidney transplantation is the treatment of choice for many patients with end-stage kidney disease.
A successful kidney transplant can improve your quality of life and reduce your risk of dying.
In addition, patients who undergo kidney transplantation do not require hours of dialysis treatment.
Ideally, patients who are eligible to get a kidney transplant do so before ever starting on dialysis.
Patient selection for HIV positive transplantation
HIV positive patients should be selected for transplantation according to standard selection criteria, such as virally suppressed, stable ART regimen, and CD4 count above 200 cells/mm3.
However, transplantation of HIV positive recipients with viral loads less than 200 cps/ml should be limited to centres with abroad experience.
Patients with fully treated tuberculosis should be considered for transplantation, while those with opportunistic infections and neoplasms without effective medical therapy are excluded.
All potential recipients should be screened for tuberculosis, syphilis and hepatitis C pre-transplant.
Treatment/screening for co-infection for HBV/HCV should be done prior to transplant.
The Pros:
Improve your quality of life.
The new kidney will help restore the body’s metabolism and improve blood circulation, allowing the body to handle nutrients better and live a healthy life.
The Cons:
Delayed graft function (DGF), AR, graft loss and days spent hospitalized in the first year after KT as well as a trend towards lower mortality.
Acute rejection.
Young age, heavy proteinuria before transplant, and rapid progress of primary FSGS are independent risk factors for recurrent FSGS.
Infectious complications
Drug interaction
Will you elaborate more on HIVAN?
HIV-related nephropathy is a major cause of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from AKI and CKD.
A full virologic cure is only possible with complete eradication of the viral reservoir in the kidney.
Renal disease associated with HIV infection is primarily a glomerular dominant disease, classified into two main categories: podocytopathies and immune complex-mediated disease.
Specific infection screening considerations in HIV positive TX
HPV screening post transplantation:
Post-TX MAY make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection.
Secondary causes should be sought in post-infectious glomerulonephritis.
HIV-associated nephropathy incidence peaked in the mid-1990s but has declined due to increased use of combined anti-retroviral treatments.
Pathophysiology:
HIV-Associated Nephropathy:
HIV-Associated Nephropathy is caused by the expression of HIV-1 genes in the kidney epithelial cells, which is mediated via transfer from leukocytes and phagocytosis of apoptotic CD4+ T cells.
Polymorphisms in APOL1 result in an increased risk of HIVAN.
HIV-Associated Immune Complex Kidney Disease
HIV-associated immune complex kidney disease is caused by co-infection with hepatitis B and C, but the mechanism and relevance of post-antiretroviral therapy is unknown.
HIV-Associated Thrombotic Microangiopathy
Thrombotic microangiopathy is caused by exposure to circulate viral proteins combined with medications, proinflammatory molecules, and antiphospholipid antibodies.
Histopathology
HIVAN it is the classic kidney disease that has been associated with HIV infection as a complication of AIDS.
Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubulo-reticular inclusion bodies, with diffuse effacement of podocyte foot process and endothelial tubular inclusions may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants.
Due to the cART, the incidence of HIVAN is declining.
Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESRD.
Patients with HIVAN have:
Advanced HIV disease with a CD4 of less than 200
Nephrotic range proteinuria
Rapid decline in kidney function
HIV-associated nephropathy is characterized by collapsing glomerulopathy and tubulointerstitial disease,
HIV-related kidney diseases fall under four pathologic classifications:
Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases.
Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial, or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis.
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis.
History and Physical:
HIV-associated nephropathy is characterized by a rapid decline in GFR and proteinuria, but other manifestations are uncommon.
Evaluation:
Screening for HIV nephropathy in HIV positive patients should include serum creatinine and estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline when ART is initiated or changed, and at least twice a year in stable patients infected with HIV.
Imaging modalities, such as ultrasonography of the kidneys, may be useful in specific settings, but a kidney biopsy is often the only means of achieving a definitive diagnosis.
CART induced nephropathy is more common than HIVAN, presenting with CD4 count <200 cells/mm, viral load >400 copies/mL, rapid decline in renal function, proteinuria >300 mg/24h, hyaline or proteinaceous casts on urinalysis, and large-sized kidneys with intense cortical echogenicity.
Diagnosis:
The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
Suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
Kidney biopsy is gold standard for diagnosis of HIVAN.
There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease.
Differential Diagnosis:
Noncollapsing focal segmental glomerulosclerosis (FSGS)
HIV-associated immune complex kidney disease
Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)
Amyloidosis
Minimal change disease
Postinfectious glomerulonephritis
Thrombotic microangiopathy
Diabetic nephropathy
Immunoglobulin A nephropathy
Membranous glomerulopathy
Differential diagnosis Collapsing glomerulopathy:
FSGS primary (idiopathic) FSGS
Parvovirus B19 infection
SV40 infection
acute CMV infection
Erythrophagocytosis syndrome
Interferon therapy
Pamidronate toxicity
Acute vaso-occlusive injury
Rare familial forms
Treatment:
HIVAN is associated with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, so
1-Combined antiretroviral therapy is the mainstay of treatment for all patients with HIV infection regardless of CD4 count.
It is important to adjust cART therapy to renal function, and renal replacement therapy remains the mainstay.
Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs) are also important, and steroids can be added as an adjunct.
SGLT2 inhibitors
Prophylactic therapy:
Prophylaxis against PCP and CMV is like regimens used at most centers for HIV negative recipients.
Vaccinations prior to transplant:
Pneumococcal vaccine given to all patients on the waiting list pre-TX.
Hepatitis A and B vaccine, if indicated, should be given before the transplant.
Influenza vaccine once yearly.
HZV vaccination in high-risk patients (>50 years old).
HPV vaccine should be given in selected patients, usually under the age of 45 years.
All patients must be up to date with DPT & MMR vaccinations before transplantation.
Vaccinations post-transplant:
Annual influenza vaccination is recommended.
Use of live virus vaccine not recommended (MMR should not be given post-transplant)
It is recommended to wait 3 to 6 months after transplant before giving vaccines.
If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment.
Immunosuppression and antiretroviral therapy challenges
Interaction between protease and non-nucleoside reverse transcriptase inhibitors with the CNI and mTOR inhibitors.
Variable drug levels between patients and often CNI dosages must be significantly increased or decreased because of these drugs on the cytochrome P450 enzyme.
Prognosis:
The prognosis in patients with HIVAN is poor, even among those treated with ART.
HIVAN consistently do worse than those with other causes of renal disease.
Many HIVAN patients will develop end-stage kidney disease (ESKD).
Complication:
HIVAN can lead to CKD, ESRD, hypertension, and lower extremity edema.
Deterrence and Patient Education:
HIV-associated nephropathy is an aggressive disease that can lead to end-stage renal disease, so patients should be encouraged to be compliant with antiretroviral medications and follow up with their primary care clinician and nephrologist on a regular basis.
Pearls and Other Issues
Combined antiretroviral therapy is the mainstay treatment for HIVAN, but other aetiologies are more common due to cART and improved survival.
An interprofessional team approach should be used to improve patient outcomes, including frequent renal function testing and biopsy.
CD4 count and viral load should be considered for cART initiation.
What are the chances of recurrence of HIVAN post-transplantation?
HIV-positive patients who underwent a second transplant had a 1.96-fold higher risk of allograft loss and a 3.1-fold increased risk of death.
The risk of recurrence of collapsing FSGS is approximately 30% after transplantation.
Prognosis is poor for HIVAN recurrence after kidney transplantation.
Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence.
HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients.
Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney.
Reference
HIV and Kidney Transplantation by Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool -UK
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013;62(2):335-338. doi: 10.1053/j.ajkd.2013.01.010
Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int 92: 461–469, 2017
Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018 May;27(3):144-152.
Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kathryn Manning, Peter Chin-Hong, Peter Stock, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies, Transplantation. 2021 July 01; 105(7): 1492–1501. doi:10.1097/TP.000000000000 3485.
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
Please counsel this patient discussing the pros and cons of transplantation.
Will you elaborate more on HIVAN?
What are the chances of recurrence of HIVAN post-transplantation?
HIV per se is not a contraindication for kidney transplantation.
End stage renal disease 2/2 HIV should be offered transplant if there CD4.
count is more than 200 cells/microliter for at least 3 months and the viral
load is undetectable for the same period and the patient has.
demonstrated compliance and has no active infection and/or malignancy.
HIV-positive patients are wait-listed only if:
a) They are adherence with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma
Please counsel this patient discussing the pros and cons of transplantation.
Pre-transplant testing and immunization, immunosuppressive protocol, post-transplant prophylaxis, risk of rejection, prognosis, long-term results, post-transplantation problems, HIV infection, and delayed graft function.
Kidney Tx. can be successful in HIV+ patients, but further studies are needed to optimize immunosuppressive therapy regimens to reduce AR after transplantation.
Kidney transplantation is the treatment of choice for many patients with end-stage kidney disease.
A successful kidney transplant can improve your quality of life and reduce your risk of dying.
In addition, patients who undergo kidney transplantation do not require hours of dialysis treatment.
Ideally, patients who are eligible to get a kidney transplant do so before ever starting on dialysis.
Patient selection for HIV positive transplantation
HIV positive patients should be selected for transplantation according to standard selection criteria, such as virally suppressed, stable ART regimen, and CD4 count above 200 cells/mm3.
However, transplantation of HIV positive recipients with viral loads less than 200 cps/ml should be limited to centres with abroad experience.
Patients with fully treated tuberculosis should be considered for transplantation, while those with opportunistic infections and neoplasms without effective medical therapy are excluded.
All potential recipients should be screened for tuberculosis, syphilis and hepatitis C pre-transplant.
Treatment/screening for co-infection for HBV/HCV should be done prior to transplant.
The Pros:
Improve your quality of life.
The new kidney will help restore the body’s metabolism and improve blood circulation, allowing the body to handle nutrients better and live a healthy life.
The Cons:
Delayed graft function (DGF), AR, graft loss and days spent hospitalized in the first year after KT as well as a trend towards lower mortality.
Acute rejection.
Young age, heavy proteinuria before transplant, and rapid progress of primary FSGS are independent risk factors for recurrent FSGS.
Infectious complications
Drug interaction
Will you elaborate more on HIVAN?
HIV-related nephropathy is a major cause of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from AKI and CKD.
A full virologic cure is only possible with complete eradication of the viral reservoir in the kidney.
Renal disease associated with HIV infection is primarily a glomerular dominant disease, classified into two main categories: podocytopathies and immune complex-mediated disease.
Specific infection screening considerations in HIV positive TX
HPV screening post transplantation:
Post-TX MAY make HPV-related cervical and anorectal illness, which is already accelerated in patients with HIV infection, worse. Close follow-up with anal & cervical PAP smears is important in the HIV positive recipient, & early detection of atypical cells with aggressive treatment can prevent the need for a major surgical resection.
Secondary causes should be sought in post-infectious glomerulonephritis.
HIV-associated nephropathy incidence peaked in the mid-1990s but has declined due to increased use of combined anti-retroviral treatments.
Pathophysiology:
HIV-Associated Nephropathy:
HIV-Associated Nephropathy is caused by the expression of HIV-1 genes in the kidney epithelial cells, which is mediated via transfer from leukocytes and phagocytosis of apoptotic CD4+ T cells.
Polymorphisms in APOL1 result in an increased risk of HIVAN.
HIV-Associated Immune Complex Kidney Disease
HIV-associated immune complex kidney disease is caused by co-infection with hepatitis B and C, but the mechanism and relevance of post-antiretroviral therapy is unknown.
HIV-Associated Thrombotic Microangiopathy
Thrombotic microangiopathy is caused by exposure to circulate viral proteins combined with medications, proinflammatory molecules, and antiphospholipid antibodies.
Histopathology
HIVAN it is the classic kidney disease that has been associated with HIV infection as a complication of AIDS.
Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubulo-reticular inclusion bodies, with diffuse effacement of podocyte foot process and endothelial tubular inclusions may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants.
Due to the cART, the incidence of HIVAN is declining.
Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESRD.
Patients with HIVAN have:
Advanced HIV disease with a CD4 of less than 200
Nephrotic range proteinuria
Rapid decline in kidney function
HIV-associated nephropathy is characterized by collapsing glomerulopathy and tubulointerstitial disease,
HIV-related kidney diseases fall under four pathologic classifications:
Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases.
Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial, or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis.
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis.
History and Physical:
HIV-associated nephropathy is characterized by a rapid decline in GFR and proteinuria, but other manifestations are uncommon.
Evaluation:
Screening for HIV nephropathy in HIV positive patients should include serum creatinine and estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline when ART is initiated or changed, and at least twice a year in stable patients infected with HIV.
Imaging modalities, such as ultrasonography of the kidneys, may be useful in specific settings, but a kidney biopsy is often the only means of achieving a definitive diagnosis.
CART induced nephropathy is more common than HIVAN, presenting with CD4 count <200 cells/mm, viral load >400 copies/mL, rapid decline in renal function, proteinuria >300 mg/24h, hyaline or proteinaceous casts on urinalysis, and large-sized kidneys with intense cortical echogenicity.
Diagnosis:
The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
Suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
Kidney biopsy is gold standard for diagnosis of HIVAN.
There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease.
Differential Diagnosis:
Noncollapsing focal segmental glomerulosclerosis (FSGS)
HIV-associated immune complex kidney disease
Membranoproliferative glomerulonephritis (associated with concurrent hepatitis C infection)
Amyloidosis
Minimal change disease
Postinfectious glomerulonephritis
Thrombotic microangiopathy
Diabetic nephropathy
Immunoglobulin A nephropathy
Membranous glomerulopathy
Differential diagnosis Collapsing glomerulopathy:
FSGS primary (idiopathic) FSGS
Parvovirus B19 infection
SV40 infection
acute CMV infection
Erythrophagocytosis syndrome
Interferon therapy
Pamidronate toxicity
Acute vaso-occlusive injury
Rare familial forms
Treatment:
HIVAN is associated with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, so
1-Combined antiretroviral therapy is the mainstay of treatment for all patients with HIV infection regardless of CD4 count.
It is important to adjust cART therapy to renal function, and renal replacement therapy remains the mainstay.
Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs) are also important, and steroids can be added as an adjunct.
SGLT2 inhibitors
Prophylactic therapy:
Prophylaxis against PCP and CMV is like regimens used at most centers for HIV negative recipients.
Vaccinations prior to transplant:
Pneumococcal vaccine given to all patients on the waiting list pre-TX.
Hepatitis A and B vaccine, if indicated, should be given before the transplant.
Influenza vaccine once yearly.
HZV vaccination in high-risk patients (>50 years old).
HPV vaccine should be given in selected patients, usually under the age of 45 years.
All patients must be up to date with DPT & MMR vaccinations before transplantation.
Vaccinations post-transplant:
Annual influenza vaccination is recommended.
Use of live virus vaccine not recommended (MMR should not be given post-transplant)
It is recommended to wait 3 to 6 months after transplant before giving vaccines.
If a patient received treatment for rejection, vaccination should be avoided for 6 months following treatment.
Immunosuppression and antiretroviral therapy challenges
Interaction between protease and non-nucleoside reverse transcriptase inhibitors with the CNI and mTOR inhibitors.
Variable drug levels between patients and often CNI dosages must be significantly increased or decreased because of these drugs on the cytochrome P450 enzyme.
Prognosis:
The prognosis in patients with HIVAN is poor, even among those treated with ART.
HIVAN consistently do worse than those with other causes of renal disease.
Many HIVAN patients will develop end-stage kidney disease (ESKD).
Complication:
HIVAN can lead to CKD, ESRD, hypertension, and lower extremity edema.
Deterrence and Patient Education:
HIV-associated nephropathy is an aggressive disease that can lead to end-stage renal disease, so patients should be encouraged to be compliant with antiretroviral medications and follow up with their primary care clinician and nephrologist on a regular basis.
Pearls and Other Issues
Combined antiretroviral therapy is the mainstay treatment for HIVAN, but other aetiologies are more common due to cART and improved survival.
An interprofessional team approach should be used to improve patient outcomes, including frequent renal function testing and biopsy.
CD4 count and viral load should be considered for cART initiation.
What are the chances of recurrence of HIVAN post-transplantation?
HIV-positive patients who underwent a second transplant had a 1.96-fold higher risk of allograft loss and a 3.1-fold increased risk of death.
The risk of recurrence of collapsing FSGS is approximately 30% after transplantation.
Prognosis is poor for HIVAN recurrence after kidney transplantation.
Only 2 patients in the South African group of 51 TXs lost their grafts out of the 12 individuals who were observed to have some HIVAN-related changes on biopsy. In the first 3 years following TX, many individuals also experienced episodes of rejection. Throughout the whole research, undetectable viral levels were seen in all patients who experienced an HIVAN recurrence. In this study group, there was no association between donor virus load & HIVAN recurrence.
HIVAN was not a clinical concern and was observed in 2/150 positive participants in the USA multicentre trial that included more than 150 HIV positive patients.
Recurrence of HIVAN is a significant concern that will require more attention in the future. Research will continue to focus on the the significance of precise location of the viral reservoir in the transplanted kidney. Canaud et al. described a rapid decline in graft function if the virus is found in the podocyte rather than the tubular cell of the transplanted kidney.
Reference
HIV and Kidney Transplantation by Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool -UK
Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013;62(2):335-338. doi: 10.1053/j.ajkd.2013.01.010
Allen PJ, Chadban SJ, Craig JC, Lim WH, Allen RDM, Clayton PA, Teixeira-Pinto A, Wong G: Recurrent glomerulonephritis after kidney transplantation: Risk factors and allograft outcomes. Kidney Int 92: 461–469, 2017
Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018 May;27(3):144-152.
Elmi Muller, Francois C. J. Botha, Zunaid A. Barday, Kathryn Manning, Peter Chin-Hong, Peter Stock, Kidney Transplantation in HIV Positive Patients: Current Practice and Management Strategies, Transplantation. 2021 July 01; 105(7): 1492–1501. doi:10.1097/TP.000000000000 3485.
Please counsel this patient discussing the pros and cons of transplantation.
PROS:
CONS:
Will you elaborate more on HIVAN?
What are the chances of recurrence of HIVAN post-transplantation?
Yes there are chances of HIVAN re currance, but exact data is lacking and needs more studies.
REF:
A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
– HIVAN is the classic kidney disease of HIV infection and commonest cause of CKD and ESRD in HIV patients ,but fortunately has become less common with widespread use of antiretroviral therapy .
– Patients with African descent has been reported prevalence of HIVAN to be 3% to 12%
– It has increasingly been recognized that APOL1 gene risk alleles play a pivotal role in the development and progression of HIVAN which may be targeted for future therapy.
1.Transl Androl Urol. 2019 Apr; 8(2): 148–154. doi: 10.21037/tau.2018.11.09
2. Kidney transplantation in HIV-positive adults: the UK experience doi.org/10.1177/0956462413493266
3. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485.
4. Johns Hopkins HIV Guide . Nephropathy, HIV-Associated (HIVAN)
5. Semin Nephrol. 2008 Nov; 28(6): 513–522. doi: 10.1016/j.semnephrol.2008.08.005
6. HIV-Associated Nephropathy in 2022 Glomerular Dis 2023;3:1–11
https://doi.org/10.1159/000526868
I agree with the figures that you have quoted for HPVAN recurrence rate, that are realistic.
Too much use of bullet points even before the headings is not a good idea. You have used bullet points with hyphen and at places where there is no word,
Thank you prof Ajay noted .
Proper patient counselling is the cornerstone of the initial steps of improving patient centered quality of life.
Starting by the pros; renal transplantation is by far the best therapeutic option for ESRD ,improving lifestyle, avoiding complications associated by dialytic support ( risk of cardiovascular complications, bone mineral disease affection, risk of repeated blood transfusion and other encountered adverse effects), achieving dependent lifestyle compared to haemodialysis. Renal transplantation has been feasible after the advances of c ART therapy and improved further success results.
While the cons that are really challenging are the following ; the increased probability of acute rejection episodes , marked susceptibility to opportunistic infections as CMV ,PCP and others which may be life threatening requiring long-term prophylactic protocols. Although there have been advances in c ART therapy, yet there are expected drug interactions among immunosuppressive medications and c ART therapy may pose the patients to hazardous risks of viral replication or the higher incidence of rejection.
HIVAN occurs mainly by the expression of HIV-1 genes within the renal epithelial cells. However the culprit mechanism is still unknown how the HIV infects renal epithelial cells. Some studies revealed that macrophages and lymphocytes seem to be vectors for renal epithelial cell transmission of HIV. The CD209 antigen (DC-SIGN) is one of the antigens studied that can directly contribute to infection of renal tubular cells mediating HIV infection of dendritic cells, and lymphocyte antigen 75 (DEC-205). Polymorphisms in APOL1 may result in an increased incidence of HIVAN. Phagocytosis of apoptotic CD4+ T cells are also suggested as one of the possible mechanisms by which HIV enters renal epithelial cells. The HIV proteins Vpr and Tat circulate in plasma as well as proteoglycans, and lipid get access to podocytes.
Screening for HIV nephropathy relies on serum creatinine, estimated glomerular filtration rate (GFR) along with urinalysis or a quantitative measure of proteinuria at baseline after c ART therapy is administered or changed for at least twice a year in stable patients. Renal biopsy remains the definitive means for diagnosis. Histologically, it resembles collapsing FSGS however the presence of tubuloreticular inclusions within the endothelial cells distinguishes them by EM.
Treatment essentially by c ART therapy in addition to ACEI to delay progression to ESRD.
Recurrence rate post renal transplantation is assumed to be high resembling FSGS about 30 %. This can be detected early on histological level in protocol biopsies without even clinical manifestations. Unfortunately according to the scares data recurrence of HIVAN may not be prevented by the use of cART therapy.
Reference
British transplantation society guidelines
https://bts.org.uk/wp-content/uploads/2016/09/05_BTS_Kidney_HIV-1.
https://www.ncbi.nlm.nih.gov/books/NBK559134/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925992/
Thanks, Samar
Elaborate more on the recurrence of HIVAN post-transplantation. I do not think that 30% recurrence rate of HIVAN is correct.
PLoS One. 2015; 10(6): e0129702.
Published online 2015 Jun 10. doi: 10.1371/journal.pone.0129702
PMCID: PMC4463848
PMID: 26061701
Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy
According to this study, among 11 patients biopsy proven HIVAN, one patient had recurrence which was biopsy proven although undetectable HIV RNA viral levels. It was suggested then that HIV can be detected in 68% of renal allografts specifically in podocytes and tubular cells. It also concluded that, the 1- and 3-year rejection rates were 18% and 27%.
Kidney transplantation is the standard of care treatment for end stage renal disease, notwithstanding the HIV status of the recipient (1).
Pros of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
Cons of transplantation in a patient on hemodialysis secondary to HIV-associated nephritis (HIVAN) include:
HIV-associated nephropathy (HIVAN) is the first kidney disease diagnosed in HIV-infected patients, having nephrotic syndrome (having collapsing form of focal segmental glomerulosclerosis, FSGS), rapid progression to end stage renal disease (ESRD), and irreversible renal failure (6).
Risk factors for HIVAN: HIVAN risk is 50 times more in African-Americans than in whites, with increased risk with presence of 2 APOL1 risk alleles (6). Other risk factors include CD$ count <200, high viral load (>400 copies/ml), proteinuria >3g per day, and eGFR<90 ml/min with elevated serum creatinine from baseline (7).
Patients clinically present with moderate to heavy proteinuria with bland urinary sediments. Edema and hypertension are not typically seen in HIVAN. Patients will present with progressively decreasing renal function, and will have high viral load and low CD4 counts signifying advanced HIV infection. Ultrasound of the kidneys reveals enlarged, echogenic kidneys, requiring a kidney biopsy to differentiate it from other causes (like diabetic nephropathy, amyloidosis, classic FSGS, membranous nephropathy, and membranoproliferative glomerulonephritis). The histopathological changes seen with HIVAN include collapsing FSGS, interstitial nephritis, visceral epithelial cell proliferation, endothelial tubuloreticular inclusions, and tubular microcystic dilatation (6).
Management of HIVAN involves initiation of cART (regardless of CD4 count), ACE inhibitors or ARBs (if no contraindication), and avoiding nephrotoxic agents. Steroids have been used to reduce tubulointerstitial inflammation, in patients with rapidly progressing renal dysfunction despite optimal RAAS inhibition and cART use. In case of ESRD development, renal replacement therapy in form of dialysis and transplant is available. Renal transplant should be offered if the patient fulfils certain criteria like CD4 count >200 and undetectable viral load (2).
The risk of HIVAN recurrence post-transplant, especially if the donor is HIV-positive has been seen (6). There is no correlation between the recurrence of HIVAN and viral loads (4). The exact location of viral reservoir in the transplant kidney with rapid worsening of renal function seen if the virus is identified in the podocyte (rather than in the tubular cell) of the transplanted kidney (8). HIVAN recurrence has not been found to be clinically relevant in a US multicenter trial (6). Since HIVAN is a secondary form of FSGS (due to HIV infection), if HIV infection is managed well with cART, the chances of recurrence are low. Hence it is important to put more emphasis on cART, and especially immunosuppressive-drug interactions in the transplant recipient.
References:
Excellent Amit as always. It is a benchmark answer.
Please counsel this patient discussing the pros and cons of transplantation.
kidney transplantation is a valid therapeutic option for HIV-positive patients with end-stage kidney disease(1).
Pros of transplantation:
1. Survival rates following kidney transplantation are higher in comparison with patients remaining on dialysis.
2. Patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation.
3. KT in HIV patient is cost-effective when compared to those remaining on dialysis.
4. Improved quality of life of PWH.
5. Better long-term prognosis of an HIV-positive patient.
Cons of transplantation:
1. Some studies report disturbingly high acute rejection rates.
2. Infectious complications following solid-organ transplantation are common and may be life- or graft-threatening.
3. Reactivation following immune suppression may occur with previously indolent infections.
4. Some of the commonly used antiretrovirals, have been associated with kidney injury and kidney disease progression.
5. EBV sero-negative recipients of an organ from an EBV seropositive transplant have a seven-fold increased risk of post-transplant lymphoproliferative disorder (PTLD).
6. High prevalence of HBV and HCV infection.
7. High rates of liver disease progression (cirrhosis, hepatocellular carcinoma) have been reported in untreated HBV co-infected patients who underwent kidney transplantation.
8. Increase the incidence of human papilloma virus (HPV)-associated cancer.
9. Increase the incidence of KS.
10.Drug-Drug interaction: Protease-inhibitors, dramatically increase CNI and mTORi exposure, thus requiring significant dose reductions( e.g. 90% CsA and 99% tacrolimus dose reduction). NNRTIs are enzyme-inducers that reduce CNI and mTOR-inhibitor drug concentrations. No significant drug interactions have been noted for CNIs or mTOR-inhibitors when co- administered with the integrase-inhibitor.
Will you elaborate more on HIVAN?
1. HIV-associated Nephropathy (HIVAN) is most prevalent in patients who receive antiretroviral therapy (ART) late after initial diagnosis, and is a major cause for CKD in developing countries(2).HIVAN almost exclusively affects persons of African descent, who account for approximately 90% of HIVAN-related cases of ESRD(3).
2. HIVAN is manifested by collapsing glomerulopathy. Kidneys are often enlarged in HIVAN patients.
3. Patients with HIVAN manifest nephrotic syndrome, often have increased serum creatinine at presentation, and show rapid progression, with about half reaching ESRD after 3 years.
4. The prevalence of HIVAN among HIV-infected individuals has decreased dramatically since the advent of combination antiretroviral therapy (cART) as standard of care for these patients.
5. HIVAN/HISTOPATHOLOGY(4):
a) Light microscopy: Segmental or global glomerular tuft collapse with overlying visceral epithelial hyperplasia and hypertrophy is seen. Hypertrophied visceral epithelial cells have frequent protein droplets. There is accompanying microcystic tubular dilatation and active tubulointerstitial nephritis with a predominantly lymphocytic infiltrate, often with tubulitis and edema.
b) Immunofluorescence microscopy: No or limited immune deposits (nonspecific IgM and C3 staining in collapsed segments) are identified. Protein droplets in visceral epithelial cells may stain for immunoglobulins and albumin.
c) Electron microscopy: Glomerular basement membranes are wrinkled and collapsed. Overlying visceral epithelial cells show hypertrophy and hyperplasia, with frequent vacuoles and protein droplets. There is extensive foot process effacement and no or limited mesangial deposits. Tubuloreticular aggregates are present in endothelial cells, in contrast to idiopathic collapsing glomerulopathy, in which such aggregates are typically absent. Tubuloreticular aggregates may be rare or even absent in patients with low viral loads who are receiving cART.
6. Key Diagnostic Features
· A clinical history of HIV infection and the presence of tubule-reticular aggregates indicate HIVAN as the etiology of the collapsing lesions.
· Extensive foot process effacement.
· Tubuloreticular aggregates in endothelial cells
· Absence of immune complex deposits
· Collapsing glomerulopathy, with collapse of tuft, segmental or global, with overlying visceral epithelial cell proliferation
· Microcystic tubular dilatation with active tubulointerstitial inflammation.
7. HIVAN/Differential Diagnosis
· Crescentic GN.
· Collapsing glomerulopathy can be related to other infections (eg, parvovirus), drugs (eg, bisphosphonates and calcineurin inhibitors), severe vascular disease (eg, thrombotic microangiopathy and cocaine use), and autoimmune disease (eg, systemic lupus erythematosus), or may be idiopathic. A clinical history of HIV infection and the presence of tubuloreticular aggregates indicate HIVAN as the etiology of the collapsing lesions.
What are the chances of recurrence of HIVAN post-transplantation?
1. The largest prospective study to date included 150 HIV-positive patients and reported patient and graft survival rates of 88% and 74% at three years, which was somewhat below that of the general US kidney transplant population(3).
2. In 2005, Kumar et al reported a study of 40 HIV-positive patients. They observed that the 1-and 2-year patient survival rates were 85% and 82%, respectively. The corresponding graft survival rates were 75% and 71%, with a 22% acute rejection rate. The HIV viral load remained undetectable, and the CD4 T cell counts were > 400 cells/mm3. No opportunistic infections or progression to AIDS were observed in these patients at 2 years. Interestingly, the authors noticed that 3 of 40 patients had HIVAN recurrence on the allografted kidney. One of these patients was asymptomatic, and the HIVAN diagnosis was made on a protocol biopsy(5).
References
1. Kidney & Pancreas Transplantation in Patients with HIV Second Edition Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017]
2. Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clin Nephrol. 2015; 837 Suppl 132-38
3. Medscape; Drugs & Diseases; Nephrology: HIV-Associated Nephropathy and Other HIV-Related Renal Disorders Updated: Mar 16, 2023 Author: Moro O Salifu, MD, MPH, MBA, MACP; Chief Editor: Vecihi Batuman, MD, FASN
4. ATLAS OF RENAL PATHOLOGY II| VOLUME 68, ISSUE 2, E13-E14, AUGUST 2016 AJKD Atlas of Renal Pathology: HIV-Associated Nephropathy (HIVAN) Agnes B. Fogo, MD Mark A. Lusco, MD Behzad Najafian, MD Charles E. Alpers, MD DOI:https://doi.org/10.1053/j.ajkd.2016.06.002
5. Kumar MS, Sierka DR, Damask AM, et al. Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients. Kidney Int. 2005;67:1622–1629.
Thanks, Safi
Looks that the recurrence of HIVAN was very small in the study you mentioned. Only 3 out of 40. What are the factors associated with the recurrence of HIVAN?
Pros and cons of transplantation
Pros
Cons
HIVAN
Recuurence after Kidney transplantation
References
1.Uptodate.com/contents/hiv-associated-nephropathy-hivan/abstract/1
Naicker S, Rahmanian S, Kopp JB. HIV and chronic kidney disease. Clin Nephrol. 2015; 837 Suppl 132–3
2. Cohen SD, Kopp JB, Kimmel PL. Kidney diseases associated with human immunodeficiency virus infection. N Engl J Med. 2017; 377:2363–2374
Thanks, Kamal
Elaborate more on the recurrence of HIVAN post-transplantation.
The recurrence of HIVAN after kidney transplantation is registered, the incidence is low but variables with different studies.
Recurrence of the disease as a classical HIVAN or another form of disease associated with HIV infection, make a burden of kidney disease on those populations.
There are many forms of kidney diseases (more noticed in ART-treated patients) but the most common form
⭐ Renal transplantation still has better survival than continuation on dialysis for HIV patients
_pros: decrease cardiovascular mortality related to dialysis
Cons.: Need for close follow up of graft function, Drug drug interaction between ART and CNI, HIV control, increased risk of opportunistic infections as CMV and PJP, higher risk of DGF and AR than HIV naive, higher risk of malignancy.
👉 👉 HIVAN is common in African population, especially with APOL 1 gene mutation.
_ can be in many forms either:.
1_ glomerular as FSGS (collapsing variant).
2_ tubulointerstitial form with ATN and tubulointerstitial nephritis.
3_ vascular form as TMA.
4_ Diabetic nephropathy or astherosclrotic vascular changes
⭐ ⭐ ⭐ The risk of recurrence of HIVAN is depending on controlling the underlying disease as HIV infection (depends on adherence to ART , presence of resistance strains, control of HIV disease as PCR and CD4 count, use of appropriate IS therapy with caution regarding drug interaction between CNI and ART….better to use integrase inhibitors not protease inhibitors )
Thanks, Mai
Tell us about the recurrence of HIVAN post-transplantation.
Thanks dear professor .
_Previous studies included that the recurrence of HIVAN is low (as FSGS is secondary to HIV infection) which is prevented by controlling HIV infection by ART.
_However, many risk factors has been associated with recurrent HIVAN as Postive HIV donor (with viral reservoir in the allograft, lower CD4 cell count, inappropriate ART adherence or drug interaction with CNI).
HIVAN is exclusive in African Americans not in white races
HIVAN is frequent in patients who are incompliant or do not receive cART therapy due to the replication of HIV in renal cells. The patient is young, and renal transplantation is beneficial after fulfilling the eligibility criteria. The patient should know that compliance with treatment (cART) is of almost importance. He should be informed about the complexity, drug-drug interaction, and risks of viral infections (like CMV & Polyomavirus). We need to make sure about the situation of immunity and CD4+ cell count (>200).
HIVAN can relapse after transplantation. In patients with HIVAN, antiretroviral treatments is initiated regardless of CD4+ cell count.
Acute rejection is also reported to be higher in HIVAN patients compared to normal population (Waheed et al.)
———-
Rivera, F. B., Ansay, M. F. M., Golbin, J. M., Alfonso, P. G. I., Mangubat, G. F. E., Menghrajani, R. H. S., … & Kazory, A. (2022). HIV-associated Nephropathy in 2022. Glomerular Diseases.
Waheed S, Sakr A, Chheda ND, Lucas GM, Estrella M, Fine DM, Atta MG. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015 Jun 10;10(6):e0129702. doi: 10.1371/journal.pone.0129702. PMID: 26061701; PMCID: PMC4463848.
Dear Mahmud
Your answer is very deficient. Please review the questions again and reply back.
Counsel this patient discussing the pros and cons of transplantation.
Though kidney transplantation is the best modalities of RRT but here counselling is necessary including pros and cons.
· About living versus deceased donor.
· Screening for all opportunistic and community acquired
infections with proper immunization.
· Screening for malignancies.
· Regarding Immunosuppression protocol for induction and maintenance along with drug interaction between HAART and CNI.
· Prophylaxis for opportunistic infection.
Pros:
· Kidney transplantation is the best form of RRT.
· Because availability of c-ART, we can Accept HIV + deceased Donor.
· With current cART, we can expect a near-normal life expectancy.
· In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation.
· Better survival than being on waiting list on dialysis.
Cons:
· The risk of acute rejection is high (>50%)
· Risk of nephrotoxicity with anti-retrovirals
· Antiretrovirals with possible drug-drug interactions with immunosuppressants.
· Increase Risk of post-transplant infections and malignancy
HIVAN:
· HIV-associated nephropathy (HIVAN) is a collapsing form of focal segmental glomerulosclerosis (FSGS) secondary to HIV.
· Involves direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host. There is strong associations of HIV with Africans and APOL1 gene polymorphisms.
· Presents with massive proteinuria and a rapid deterioration of renal function.
· Suspicion is high when CD4 cell count <200, HIV viremia and Nephrotic Syndrome.
· Kidney biopsy is gold standard for diagnosis of HIVAN.
· For patients with HIVAN, ART should be initiated as soon as possible if not already taking. Medication adherence should be assured.
· Poor prognosis.
Chances of recurrence of HIVAN post-transplantation:
There are chances of recurrence in the graft post-transplantation, particularly if the donor is HIV positive
References:
1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015.
2. Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
3. DAqati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998; 18:406.
4. Winston JA, Bruggeman LA, Ross MD, et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001; 344:1979.
Thanks, will you elaborate more on the recurrence of HIVAN post-transplantation?
Please counsel this patient discussing the pros and cons of transplantation.
Prerequisite for recipient are
CD4 of more than 200
HIV viral load of less than 50 RNA copies /ml.
Adherent to ART medications.
No history of active infection
Pros of transplanation are
Better quality of life
Better survival than being on waiting list on HD/PD
Good graft survival
Aproximate graft survival during the 1-year and 3-year mark was 90% and 74%, respectively)
Cons of transplantation are
More chances of rejection
More chance of DGF
More post-transplant infections
Need of more post-transplant prophylaxis
Have Drug interactions between HAART and immunosuppression needing drug monitoring
More chances of post-transplant malignancies
Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN) usually begins with large amounts of protein in the urine and progresses rapidly to total kidney failure. HIVAN is very uncommon in people whose HIV is effectively controlled by antiretroviral (ARV) drugs. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load, and low CD4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV-positive patients. However, has been reported in Caucasian, there are few cases report. Renal parenchymal injury is characterized by epithelial cell proliferation, de differentiation and apoptosis along the entire nephron.
HIV-related kidney diseases fall under four pathologic classifications.
Glomerular-dominant nephropathies: HIVAN and immune complex–mediated glomerular diseases
Tubulointerstitial-dominant nephropathies: HIVAN-related tubulointerstitial injury; ART-induced acute tubular injury; drug-induced (other than ART) tubulointerstitial nephritis; direct renal parenchymal infection by viral, bacterial or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis.
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis
Clinical manifestations
Nephrotic-range proteinuria
Rapid decline in kidney function
Hematuria
Hypertension
Edema
Management
Combined antiretroviral therapy.
ACE inhibitor or ARB
Steroid as an Adjunct
What are the chances of recurrence of HIVAN post-transplantation?
In the South African group of 51 transplants, 12 patients were reported to have some HIVAN related changes on biopsy, but only 2 patients lost their grafts as a result. These patients also had episodes of rejection in the first 3 years after transplantation.
References
1) Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients [published correction appears in N Engl J Med. 2011 Mar 17;364(11):1082]. N Engl J Med. 2010;363(21):2004-2014. doi:10.1056/NEJMoa1001197
2) Swanepoel CR, Atta MG, D’Agati VD, Estrella MM, Fogo AB, Naicker S, et al. Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018 Mar. 93 (3):545-559.
3) Yalavarthy R, Smith ML, Edelstein CL. HIV-associated nephropathy in Caucasians: case report and review of literature. Int J STD AIDS. 2008 Nov;19(11):789-90. doi: 10.1258/ijsa.2008.008091. PMID: 18931278.
4) Waheed S, Sakr A, Chheda ND, Lucas GM, Estrella M, Fine DM, Atta MG. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015 Jun 10;10(6):e0129702. doi: 10.1371/journal.pone.0129702. PMID: 26061701; PMCID: PMC4463848.
5) Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
Thankyou.
Please counsel this patient discussing the pros and cons of transplantation.
Kidney transplantation is the best form of treatment for ESRD. It is better outcomes if proper medical , surgical and psychological workup is done. Kidney transplantation in HIV positive patients was not a common entity but this has changed in recent years. Transplantation in HIV patients has better outcomes than dialysis. Graft outcomes are better with new HAART medications. I will counsel the patient about renal transplantation by telling about pros and cons of transplant.
Benefits of transplant
Better quality of life
Less deaths due to CVD
Better outcomes
Cost effective
Hormonal and metabolic kidney functions restored
Disadvantages of Kidney transplant
Higher rejection rates
High risk of drug interactions and nephrotoxicity
Higher malignancy rates
Will you elaborate more on HIVAN?
It is commonest cause of ESRD in HIV positive patients and can lead to severe form of CKD. Renal disease remains one of the major causes of mortality in patients infected with HIV, with a six-fold increase in mortality for those suffering from acute kidney injury (AKI) and chronic kidney disease (CKD). In Black population it is associated with APOL 1 Gene mutation. Lesions resulting directly from intrarenal HIV gene expression and injuries secondary to co morbidities, drug-induced nephrotoxicity, and immune dysregulation, are some of the leading factors. With HAART the incidence has decreased .
Histology
Collapsing glomerulopathy and associated tubulointerstitial disease, which may include tubular microcysts and inflammation of the interstitium. Diffuse effacement of podocyte foot process and endothelial tubular inclusions are mainstays.
Differential diagnosis
Diagnosis
Serum creatinine and estimated glomerular filtration rate (GFR)
Urinalysis or a quantitative measure of proteinuria
Ultrasonography of the kidneys
Kidney biopsy
Management?
Combined antiretroviral therapy continues to be the mainstay of treatment
Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
In refractory renal impairment after cART and RAAS blockade treatment, steroids can be added as an adjunct
In ESRD, renal replacement therapy remains the mainstay of management, and renal transplantation can be considered
What are the chances of recurrence of HIVAN post-transplantation
I could find exact data or evidence on this. After HIVAN recurrence prognosis is poor
Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
Thankyou.
· Please counsel this patient discussing the pros and cons of transplantation.
Renal transplantation is the treatment option for fit patient with life expectancy is >5 years.
Pros:
1-Better survival than being on waiting list on dialysis.
2-HIV infection remained well controlled by cART.
3-Improving QOL.
4-Decreasing cost of RRT.
Cons:
1-Increased risk of acute rejection.
2-Reduction of CD4 count sometimes with ATG use.
3-Incresaed risk of infections.
4-Drug interaction between Immunosuppression and cART.
5-Co-infection with HCV is associated with more serious infection.
6-Higher rates of DGF.
· Will you elaborate more on HIVAN?
HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS.
The commonest cause of CRF is HIV-associated nephritis (HIVAN). Exclusive in BLACK RACE, the most common form is collapsing FSGN, and is considered the third leading cause of CKD in Blacks.
The pathogenesis of HIVAN is hypothesized to involve several factors:
1-Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells
2-Host factors, including genetic susceptibility.
In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN.
Presented by :
A-Sever advanced HIV disease.
B-Nephrotic-range proteinuria.
C-Rapid decline in kidney function.
HAART (Highly Active Anti-retrovirus Therapy),also called cART (Combination Anti-Retrovirus Therapy), can be given as single agent (ART) has improved the prognosis of HIV patients.
Treatments that have been examined for patients with HIVAN include
1-Antiretroviral therapy (ART).
2-Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
3-Glucocorticoids.
But still no randomized control studies shown the definitive plan of management.
· What are the chances of recurrence of HIVAN post-transplantation?
No enough data clarifying this point , but one study shown that kidney transplant appears effective in patients with HIVAN despite elevated rates of DGF and no recurrence detected post kidney transplant and further studies are needed to evaluate this issue(2).
References:
1- Malat GE, Boyle SM, Jindal RM, et al. Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience. Am J Kidney Dis. 2019;73(1):112-118. doi:10.1053/j.ajkd.2018.02.352.
2- Waheed S, Sakr A, Chheda ND, et al. Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy. PLoS One. 2015;10(6):e0129702. Published 2015 Jun 10. doi:10.1371/journal.pone.0129702
Well done.
· HIV per se is not a contraindication for kidney transplantation
· HIV-positive patients are wait-listed only if:
a) They are concordant with treatment, particularly cART therapy
b) Their CD4+ T cell counts are >100 cells/μL (ideally > 200 cells/ μL) and have been stable during the previous 3 months
c) HIV RNA has been undetectable during the previous 6 months
d) No opportunistic infections have occurred during the previous 6 months
e) They have no history of progressive multifocal leukoencephalopathy, chronic
intestinal cryptosporidiosis, or lymphoma
pros
· outcomes for patient with HIV are favorable, with transplantation providing a clear survival benefit over renal replacement therapy
· availability of cART has made it feasible to offer kidney transplantation to HIV-positive patients with better survival and better graft out come
· Because all patients had viral suppression and CD4þ cell counts at least 200 cells/ml prior to transplant and combination ART and post- transplant anti-infective prophylaxis was employed, HIV control was excellent, and few opportunistic infections were encountered.
Cons
· patient with HIV experienced high rates of delayed allograft function (this did not appear to be predictive of graft failure. Finally,
· HIV recipients experienced allograft rejection rates two to three times higher than observed in the general kidneytransplant population
· Bacterial infec tions were observed with increased frequency in HIV recipients who were treated with antithymocyte globulin (ATG) or coinfected with HCV.
· Classic HIVAN, as originally described in the pre-ART era continues to occur among ART-naïve or non-adherent patients, usually of African descent, irrespective of the mode of HIV transmission.
· Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV positive patients.
· Pathologically HIVAN is defined by a collapsing glomerulopathy and attendant tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation, variable acute tubular injury, and endothelial tubuloreticular inclusions by electron microscopy.2 Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions (“interferon footprints”) are classic features.
· In patients with classic HIVAN, the following features are usually present:
●Advanced HIV disease – Patients with HIVAN typically have a CD4 count less than 200 cells/microL.
●Nephrotic-range proteinuria
●Rapid decline in kidney function –
Other manifestations, such as hematuria, hypertension, and edema, may also be present
diagnosis
Kidney biopsy is currently the only way to establish a definitive diagnosis of HIVAN
Differential diagnosis
●Noncollapsing focal segmental glomerulosclerosis (FSGS) –
●Immune complex-mediated glomerulonephritis, including immunoglobulin A (IgA) nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, and a “lupus-like” proliferative glomerulonephritis.
●Glomerulonephritis due to coinfection with hepatitis C or hepatitis B virus..)
●Diabetic kidney disease, amyloidosis, or other noninfectious glomerulopathies
Treatment
· Antiretroviral therapy for all patients — All patients with HIV infection should receive ART, regardless of CD4 count.
· Additional therapies for proteinuria or hypertension (ACE inhibitors or ARBs )
· SGLT2 inhibitors
HIVAN recurrence is a concern HIV positive transplant programs.
In the South African group features of HIVAN presented many years after the transplant and had a slow progression having no clinical impact in most cases. In the South African group of 51 transplants, 12 patients were reported to have some HIVAN related changes on biopsy, but only 2 patients lost their grafts as a result. These patients also had episodes of rejection in the first 3 years after transplantation. All patients who had HIVAN recurrence had undetectable viral loads all through the study.
In the USA multicentre trial reporting on more than 150 HIV positive patients, HIVAN was not a clinical issue and was observed in 2/150 positive patients
Thankyou, well done.
All patients with HIV and ESKD should be offered transplant if there CD4 count is more than 200 cells/microliter for at least 3 months and the viral load is undetectable for the same period of time and the patient has demonstrated compliance and has no active infection and/or malignancy
The pros of transplantation include:
The cons include:
HIVAN:
It is the classic kidney disease that has been associated with HIV infection as a complication of AIDS. Histologically, it is a collapsing form of FSGS accompanied by microcytic tubular dilatation and interstitial inflammation. Tubuloreticular inclusion bodies may also be identified by electron microscopy It mainly affects the Black African race due to the presence of the APOL1 risk variants. Due to the cART, the incidence of HIVAN is declining. Survival of patients with ESKD attributed to HIVAN has also improved although it remains lower than that of non-HIV patients with ESKD.
Patients with HIVAN have:
The treatment of HIVAN includes:
Risk of Recurrence:
The risk of recurrence of collapsing FSGS is approximately 30% after transplantation
Organ Transplantation In Persons With HIV. AIDS 2020, 34:1107–1116
Please specify your references where they were used.
SGLT2 inhibitors? please supply a reference for that!
Thank you Professor Dawlat
The use of SGLT2 inhibitors for non diabetic proteinuria is extrapolated from the post hoc analysis of the DAPA CKD trial which showed a positive benefit in patients with Glomerulonephritis especially IgA nephropathy and FSGS
The EMPA Kidney trial also showed benefit in non diabetic patients with CKD and Glomerulonephritis
The SGLT2 inhibitors are used as an add on if the RAAS blockade is not controlling the proteinuria in IgA nephropathy and FSGS
– Please counsel this patient discussing the pros and cons of transplantation.
Patient counselling
Recipients have to have CD4 count >200 cells/µL, an HIV viral load <50 HIV-1 RNA copies/mL, demonstrate adherence to HAART, and free of AIDS-defining illnesses.
HIV-positive transplant candidates should have the standard consent as other recipients
the recipient is encouraged to inform their diagnosis of HIV to their donor
Pros
-Kidney transplantation in HIV-positive recipients is associated with marvellous 1-year and 3-year recipient and allograft survival rates, intermediate to those observed in the overall US kidney transplant population and in a higher risk subgroup of recipients ≥65 years also suggest good 5- and 10-year outcomes, with an improvement in survival compared with patients who remain on the waiting list.
-The adjusted relative mortality risk at five years was 79% lower among transplant recipients compared to remaining on dialysis
-response to antiviral therapy have favourable results
Cons
-More liable to severe infection specially after immunosuppression with high risk of reactivation
-Insufficient anti-viral treatment to completely suppress viral replication can lead to
emergence of drug-resistant viral escape mutants.
– HIVAN recurrence is a concern in some HIV positive transplants
-Drug -drug interaction between antiviral agents and immunosuppressives
– more liabile for rejection and delayed graft function
-Will you elaborate more on HIVAN?
HIVAN ,is primarily occurring in -naïve or non-adherent patients before ART .
Also common in patients who receive antiretroviral therapy (ART) late after initial diagnosis resulting in progression to organ failure
It’s associated with Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load and low CD-4 count.
Diagnosed by a nephrotic range proteinuria, and increased renal echogenicity on ultrasound and a kidney biopsy.
Pathologically presented by a collapsing glomerulopathy and tubulointerstitial disease, including tubular microcyst formation, interstitial lymphoplasmacytic inflammation and endothelial tubuloreticular inclusions by electron microscopy.
It’s classic features are Diffuse podocyte foot process effacement and many large endothelial tubuloreticular inclusions .
HIVAN recurrence can occur in some HIV cases.
Treated by antiretroviral therapy ,some studies used ACEI and steroids
-What are the chances of recurrence of HIVAN post-transplantation?
HIVAN recurrence can occur in some cases and need further studies as there is no sufficient data . The exact location of the viral reservoir in the transplanted kidney is crucial . A study demonstrated a rapid deterioration in graft function after the diagnosis of HIVAN if the virus is identified in the podocyte not in the tubular cell of the transplanted kidney
Reference
-Salifou M O etal . HIV-Associated Nephropathy and Other HIV-Related Renal Disorders ,Medscape 2022
– Locke JE, Gustafson S, Mehta S, et al. Survival Benefit of Kidney Transplantation in HIV-infected Patients. Ann Surg. 2017;265(3):604-608.
– Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021;105(7):1492-1501.
– Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014;25(2):407-419.
Well done but please write the number of the reference where it was used.
Please counsel this patient discussing the pros and cons of transplantation.
Pros
o Kidney transplantation is better than dialysis
o The access is the same to living donor kidney transplantation as non-infected patients
o HIV per se is not a contraindication for kidney transplantation and HIV-positive patients are wait-listed only if in specific cases including concordance with treatment
o With current cART, we can expect a near-normal life expectancy
o In carefully selected HIV-positive patients, patient and graft survival is similar to non-HIV patients at 1 and 3 years after transplantation
o Careful immuno-virological and antiretroviral status review with serologic testing for syphilis, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, human T-cell leukaemia virus, Toxoplasma gondii, latent Mycobacterium tuberculosis infection and viral hepatitis
Cons
o The risk of acute rejection is high (>50%)
o Possible nephrotoxicity with retrovirals
o Antiretrovirals with possible drug-drug interactions with immunosuppressants
o Lifelong prophylaxis against Pneumocystis pneumonia and other prophylaxis therapy
o Drug-resistance after transplantation
o Patients with HIV infection are unsuitable to be living kidney donors
o Transplantation using organs from HIV-infected individuals is restricted to organs from deceased donors with specific criteria
Will you elaborate more on HIVAN?
It is the most severe form of CKD and the commonest cause of ESRD in HIV-positive patients in the UK
o Black are at increased risk (Exclusive in BLACK RACE): 10-13% of African-Americans carry two APOL1 risk alleles, associated with a 7-10 fold increased risk of kidney disease including HIVAN
o Typically young (mean age 36 years)
o With severe immune deficiency (median CD4 cell count 66 cells/µL) and advanced kidney failure (median eGFR] 21 mL/min/1.73m2) at diagnosis
o Majority of patients progress to ESRD within 10 years of diagnosis of HIVAN
Pathophysiology:
Characterized by a collapsing glomerulopathy with active tubulointerstitial inflammation. The collapse of glomerular basement membranes is usually observed, along with hypertrophy and hyperplasia of the overlying glomerular epithelial cells, as well as active tubulointerstitial disease manifested by microcytic tubular dilatation, interstitial inflammation and tubular injury
Presentation: Rapid rise in serum creatinine and proteinuria
Differential diagnosis Collapsing glomerulopathy:
1. FSGS primary (idiopathic) FSGS
2. parvovirus B19 infection
3. SV40 infection
4. acute CMV infection
5. erythrophagocytosis syndrome
6. interferon therapy
7. pamidronate toxicity
8. acute vaso-occlusive injury
9. rare familial forms
10. glomerular injury in the renal allograft associated with microvascular disease
Recent studies on renal transplantation in patients with HIVAN have shown favorable results. Graft survival during the 1-year and 3-year mark was 90% and 74%, respectively. Graft rejection is also a major concern in this population, given the baseline immune dysregulation and the drug interactions between cART and calcineurin inhibitors
What are the chances of recurrence of HIVAN post-transplantation?
There is a risk of HIVAN recurrence in the graft posttransplantation, particularly in cases wherein the donor is HIV positive
References
1. Kidney & Pancreas Transplantation in Patients with HIV, BTS guidelines, March 2015.
2. Kumar RN, Stosor V. Organ transplantation in persons with HIV. AIDS. 2020 Jul 1;34(8):1107-1116. doi: 10.1097/QAD.0000000000002518. PMID: 32167973.
3. Sawinski, Deirdre. Kidney Transplantation in Patients with HIV. Kidney360 1(7):p 705-711, July 2020. | DOI: 10.34067/KID.0002112020
4. Werbel WA, Durand CM. Solid Organ Transplantation in HIV-Infected Recipients: History, Progress, and Frontiers. Curr HIV/AIDS Rep. 2019 Jun;16(3):191-203. doi: 10.1007/s11904-019-00440-x. PMID: 31093920; PMCID: PMC6579039.
5. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in ChronicKidney Disease. Kidney Int. 2022;102(6S):S129–S205.
6. Palau L, Menez S, Rodriguez-Sanchez J, Novick T, Delsante M, McMahon BA, Atta MG. HIV-associated nephropathy: links, risks and management. HIV AIDS (Auckl). 2018 May 25;10:73-81. doi: 10.2147/HIV.S141978. PMID: 29872351; PMCID: PMC5975615.
7. Wyatt CM, Klotman PE, D’Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol. 2008 Nov;28(6):513-22. doi: 10.1016/j.semnephrol.2008.08.005. PMID: 19013322; PMCID: PMC2656916.
Thankyou but please write the number of the reference in the corresponding place in your text.
counsel this patient
discussing the pros and cons of transplantation.
Recipient with HIVAN candidate for kidney transplantation needs counselling for.
-Absolute and relative contraindications for kidney transplantation,
-Options available for living versus deceased donor,
-Will need Pre transplant screening for all opportunistic and community acquired
infections and malignancies and proper immunization,
-Details regarding Immunosuppression protocol for induction and maintenance,
-Drug interaction between HAART & CNI and its complications,
-Prophylaxis for opportunistic infection and close surveillance for malignancies after
Transplantation,
–Kidney allograft function / HIV viral control after transplant with close monitoring, with
relative risk of rejection / infection / malignancy post KT,
-Prognosis of Transplant in HIV patients
-Risk of long-term outcomes of renal transplantation in patients with HIVAN,
Pros:
Cons:
Elaborate more on HIVAN?
Overview.
-first described in 1984 as a complication of AIDS with Renal disease, although HIVAN may also occur in patients following acute seroconversion.
-HIV-associated nephropathy (HIVAN) is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation secondary to HIV.
Pathogenesis.
-It involves direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host. The strong associations of HIV with African ancestry and APOL1 gene polymorphisms illustrate the importance of host genetic factors.
Clinical manifestations.
–HIVAN presents with heavy proteinuria and a rapid decline in kidney function.
Diagnosis.
-The diagnosis of HIVAN is suspected when patient presents with nephrotic-range proteinuria and rapidly declining kidney function with active HIV infection.
-suspicion is high when CD4 cell count <200 cells/microL with HIV viremia, and/ Nephrotic Syndrome.
-Kidney biopsy is gold standard for diagnosis of HIVAN.
-There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease.
–
Treatment.
Prognosis.
-The prognosis in patients with HIVAN is poor, even among those treated with ART.
-Many such patients will develop end-stage kidney disease (ESKD).
3-What are the chances of recurrence of HIVAN post-transplantation?
-Insufficient knowledge regarding recurrence of HIVAN but could be in the same way as conventional FSGS, which can be as high as 30% in first grafts
-As the process of FSGS is secondary in nature there is no proven increased Risk of Recurrence post-Transplant
References;
Well done.
Please counsel this patient in discussing the pros and cons of transplantation.
Kidney transplantation is still the best option for an HIV-related ESRD candidate compared to long waiting on dialysis with excellent graft and patient survival based on the available evidence for the last 15 years considering carefully selected HIV candidates who medically fit, with a life expectancy > 5 years and there is no contraindication for the transplantation which means he had persistent low viral load < 50 copies for more than 3 months, C4D count > 200 cells for 6 months, no evidence of active infection including no serious infection for last the 6 months, negative viral screen for HBV, HCV, and VZ, no active malignancy
Good adherence to c ART and tolerated well with no evidence of resistance, three specific conditions should be highlighted and discussed with HIV-positive recipients including the drug-drug interactions after transplantation, the higher rate of rejection including steroid-resistant rejection, and the HIV AN recurrence after transplantation while the opportunistic infection and malignancy found to be of similar rate for non-HIV candidates and usually they will be covered with longer chemoprophylaxis protocols after transplantation
We have to screen the donor for the possibility of HIVAN like proteinuria, hematuria, HIV associated with wide spectra glomerular diseases like HIVAN, IC-mediated nephropathy, infection or drug-induced interstitial nephritis, and TMA, we need to screen for microalbuminuria or assess the grade of proteinuria, and kidney biopsy, HIVAN more in black African American ethnicity with associated APOL1 gene mutation with risk of recurrence after transplantation, reported from some centers like in France series and south Africa but recurrence of HIV nephropathy was not problematic in the US series and they found no correlation between the viral load and the recurrence of HIVAN. Canaud et al describe a rapid deterioration in graft function after the diagnosis of HIVAN if the virus is identified in the podocyte rather than in the tubular cell of the transplanted kidney (4).
Will you elaborate more on HIVAN?
HIVAN was first described in 1984 Classic HIVAN, as first defined in the pre-ART era remains to occur among ART-naïve or non-adherent patients, usually of African origin, regardless of the mode of HIV transmission. Apoliprotein-L1 (APOL1) genetic polymorphism, high viral load, and low CD-4 count had been linked to a higher clinical risk for developing HIVAN in the native kidneys of HIV-positive patients and presenting with heavy proteinuria, mostly in the nephrotic range with progressive renal impairment and ESKD. The diagnosis requires kidney biopsy and typically presents with collapsing focal segmental glomerulosclerosis, Tubulointerstitial inflammation, and microcyst formation in the tubulointerstitial region Tubulointerstitial disease is an invariable component of HIVAN and often appears out of proportion to the severity of the glomerular disease, the clinical hallmark of HIVAN is heavy proteinuria and enlarged swelling echogenic kidneys by the US, predominant in males with low C4D, high viral load, and microalbuminuria is an early indicator of HIVAN, In USA affect black from African ethnicity in around 3-12%, It has become the third most common cause of ESRD in young people of African descent in the US(3), however with the use of C ART the prevalence of HIVAN has been declined and biopsy finding more with FSGS ( nos ) with low or undetectable viral load and nonspecific histological finding in the biopsy that difficult to be different from aging arteriolosclerosis or APLO1 glomerulosclerosis(5).
What are the chances of recurrence of HIVAN post-transplantation?
According to the available evidence from many cohort studies from the US, France, and South Africa regarding the recurrence of HIVAN with diverse results that need further studies in the future focusing on the risk of recurrence related to the time of viral replication in the kidney tissues at the time of treatment of acute rejection
(a flare-up of the viral reservoir in the kidney secondary to aggressive immunosuppression)
Back to the case he is a young HIV-positive recipient with HIVAN as ESRD on dialysis with no doubt will encourage him to go for kidney transplantation from either HIV negative donor or HIV-positive DD provided he accepts the offer and he is medically fit according to the above eligibility criteria and he is adherence to ART with no history of resistance or poor compliance and if he is from African ethnic background better to screen for APOL1 gene mutation, monitor for HIVAN recurrence with proteinuria and work up for proteinuria and consider protocol biopsy after transplantation based on center policy. address the drug-drug interaction and risk of rejection after transplantation and need MDT approach and combined FU with HIV specialist, transplant team regarding the c ART type ( avoid PI) and the viral load and C4D monitoring, prolong chemoprophylaxis for CMV, PJP , fungal infection
References
1. Rivera FB, Ansay MFM, Golbin JM, Alfonso PGI, Mangubat GFE, Menghrajani RHS, Placino S, Taliño MKV, De Luna DV, Cabrera N, Trinidad CN, Kazory A. HIV-Associated Nephropathy in 2022. Glomerular Dis. 2022 Oct 24;3(1):1-11. doi: 10.1159/000526868. PMID: 36816427; PMCID: PMC9936764.
2. Zheng X, Gong L, Xue W, Zeng S, Xu Y, Zhang Y, Hu X. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther. 2019 Nov 20;16(1):37.
3. Ma L, Divers J, Freedman BI. Mechanisms of injury in APOL1-associated kidney disease. Transplantation. 2019;103(3):487–492.
4. Canaud G, Dejucq-Rainsford N, Avettand-Fenoel V, et al. The kidney as a reservoir for HIV-1 after renal transplantation. Journal of the American Society of Nephrology : JASN. 2014;25(2):407–19.
5.Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501
Exellent answer .
IT is CD4 .
yes prof typo mistake , thank you
Please counsel this patient discussing the pros and cons of transplantation.
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Will you elaborate more on HIVAN?
Specific infection screening considerations in HIV positive TX
HPV screening post transplantation:
Prophylactic therapy:
Vaccinations post-transplant:
Immunosuppression & antiretroviral therapy challenges
=============================
What are the chances of recurrence of HIVAN post-transplantation?
References
Thank you so the recurrence if it happens de novo has no correlation with:
R viral load.
D viral status.
Is there a relation with IS ,induction choice.
Drug interactions with ART.
Please counsel this patient discussing the pros and cons of transplantation.
The HIV per se is not a contraindication for kidney transplantation, however the viral status should be controlled by a c-ART ( compliant to treatment, CD4 >100 cells/µL- ideal > 200 cells/ µL for the last 3 months, undetectable HIV RNA in the last 6 months, no opportunistic infection in the last 6 months, no PML, lymphoma or intestinal cryptosporidiosis) and an infectious disease specialist to be included in management pre and post transplantation for choosing best treatment and avoiding drug-drug interaction.
HIV viremia post transplant is possible, but controlled by c-ART.
The risk of opportunistic infection and mortality is common in the first 6 months post transplant and may be fatal.
Viral screen is a must, co infection with hepatitis C has a deleterious outcome:
Evidence of current vaccine induced or natural immunity to: Diphtheria, tetanus and pertussis (DTP), Measles, mumps and rubella (MMR), Pneumococcus, Haemophilus influenza, Meningococcus B, Influenza, VZV, Hepatitis A and, Hepatitis B (for HBsAg, HBcAb, negative patients), Human papilloma virus (HPV) vaccine is offered to patients at risk of HPV, and Strongyloides stercoralis infection prior to transplantation
PROS:
Transplantation improves quality of life and survival compared of being on HD.
Transplantation can be from a living or cadaveric donors with special criteria for selection of donors.
Transplantation in these patients can be safe when the HIV is controlled by c-ART.
CONS:
There is an increased risk of acute rejection in HIV patients.
There is an increased risk of infections especially in the first 6 months, and may be fatal.
There is an increased risk of malignancy.
There is an increased risk of delayed graft function.
Requiring multidisciplinary team (infectious disease, pharmacologist, transplant physician) concerning drug-drug interaction.
Will you elaborate more on HIVAN?
HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS), accompanied by microcystic tubular dilatation, Tubuloreticular inclusions, pseudocrescent formation and interstitial inflammation.
Africans are more commonly experiencing HIVAN, with APOL1 risk variants having higher incidence.
c-ART reduce the incidence of HIVAN, decrease progression to ESRD, and improve survival.
The pathogenesis of HIVAN is hypothesized to involve several factors:
1. Infection of kidney epithelial cells by HIV and expression of HIV genes within nfected kidney cells.
2. Host factors, including genetic susceptibility.
Clinical manifestations:
Hematuria, hypertension, edema, rapidly progressive GN, nephrotic range proteinuria, usually in patients with CD4 T cell < 200.
DDx: other viral infections- Corona viruses, light chain disease, MPGN, lupus nephritis, crescentic GN.
Diagnosis: only by kidney biopsy.
Treatment: c-ART + ACEi/ARBs+/- SGLT2i + statins, No rule for steroids
Transplantation: there is an increased risk of HIVAN recurrence after renal transplantation, and marked increased risk of acute rejection.
What are the chances of recurrence of HIVAN post-transplantation?
There is an increased risk of HIVAN recurrence after renal transplantation, and marked increased risk of acute rejection (3 folds more than non HIV infected patients) or lupus like glomerulonephritis with rapidly progressive GN.
References:
(1) Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int. 1999 Dec;56(6):2203-13. doi: 10.1046/j.1523-1755.1999.00769.x. PMID: 10594796.
(2) Selhorst P, Combrinck CE, Manning K, Botha FCJ, Labuschagne JPL, Anthony C, Matten DL, Breaud A, Clarke W, Quinn TC, Redd AD, Williamson C, Muller E. Longer-Term Outcomes of HIV-Positive-to-HIV-Positive Renal Transplantation. N Engl J Med. 2019 Oct 3;381(14):1387-1389. doi: 10.1056/NEJMc1903013. PMID: 31577883.
(3) HIV and Kidney Transplantation lecture,By Ahmed Halawa Consultant Transplant Surgeon Associate Professor, University of Liverpool –UK
(4) Kidney & Pancreas Transplantation in Patients with HIV Compiled by a Working Party of The British Transplantation Society March 2015 [Minor Revision January 2017] Second Edition
Thank you for this overview. With the risk of opportunistic infections do these patients require different antimicrobial prophylaxis post transplants compared to those with
HIV-ve recipients?
You referred to increased risk of HIVAN recurrence, can you support your answer with an appropriate reference?
Thank you Prof. Mohsen
antimicrobial prophylaxis is recommended life long for PCP, but for CMV it is the same as HIV-ve recipients.
Reference- HIVAN:
Chandran S, Jen KY, Laszik ZG. Recurrent HIV-associated immune complex glomerulonephritis with lupus-like features after kidney transplantation. Am J Kidney Dis. 2013 Aug;62(2):335-8. doi: 10.1053/j.ajkd.2013.01.010. Epub 2013 Mar 5. PMID: 23481367; PMCID: PMC4121438.
Please counsel this patient, discussing the pros and cons of transplantation, and elaborate more on HIV/AIDS.
In patients with HIV, pre-transplant evaluation takes into consideration the risk of recurrence and the risk of complications. Evaluation includes pre-transplant assessment of viral load, immunosuppressive management, post-transplant prophylaxis, immunizations, rejection risk, and delayed graft function.
HIV-positive kidney transplantation can minimize AR, but more research is needed to optimize immunosuppressive medications. Many end-stage renal disease patients choose kidney transplantation. Kidney transplants can extend life and enhance quality. Kidney transplant patients do not require dialysis.
HIV-positive individuals with stable ART regimens and CD4 counts above 200 cells/mm3 should be transplanted. Nevertheless, only internationally experienced centers should transplant HIV-positive recipients with virus loads under 200 cps/mL.
Opportunistic diseases and untreated neoplasms should not be transplanted, although fully treated tuberculosis should. Pre-transplant screenings should include tuberculosis, syphilis, and hepatitis C. Before transplant, treat or screen for HBV/HCV co-infection.
In this group, the benefits of kidney transplantation include an improvement in quality of life.
The replacement kidney will aid in restoring the body’s metabolism and enhancing blood circulation, enabling the body to better process nutrients and live a healthy life.
Disadvantages include delayed graft function, the chance of graft rejection and loss, and an increased risk of hospitalization. Other side effects include infectious problems and possibly drug-drug interactions.
What are the chances of recurrence of HIV/AIDS post-transplantation?
The risk of recurrence increases in settings of uncontrolled infection.
There are several histological forms of HIV-related kidney disease. The most common form is the collapsing form of FSGS. Other forms include immune complex-mediated glomerular disorders, HIVAN-related tubulointerstitial damage, and vascular-dominant nephropathies.
In patients with controlled HIV disease and a low viral load, the recurrence of HIVAN is negligible.
Thank you Dr Habli
I can see that you concentrated on the HIV recurrence and opportunistic infections. What about the overall graft and patient survival in the presence of these risks. Is it hugely different from general population or close to it with the benefits outweigh these risks. Please quote the appropriate supporting references.
5. A 35-year-old CKD patient on HD secondary to HIVAN (HIV-associated nephritis) came to see you in your clinic to discuss renal transplantation.
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Please counsel this patient discussing the pros and cons of transplantation.
Patient selection for HIV positive transplantation
The pros:-
The cons ;-
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Will you elaborate more on HIVAN?
====================================================================
Pathophysiology
HIV-Associated Nephropathy
HIV-Associated Immune Complex Kidney Disease
HIV-Associated Thrombotic Microangiopathy
Histopathology
History and Physical
Evaluation
Treatment / Management
Differential Diagnosis
Prognosis
Complication
Deterrence and Patient Education
Pearls and Other Issues
====================================================================
What are the chances of recurrence of HIVAN post-transplantation?
====================================================================Reference
Thank you, Mahmoud
What are the other forms of HIVAN?
You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
Many thanks for your suuport and advice Prof.Halawa
What are the other forms of HIVAN?
HIV-related kidney diseases fall under four pathologic classifications :
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Has it been reported in the Caucasian population?
I searched did not find
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Reference
1-Please counsel this patient discussing the pros and cons of transplantation.
Recipient with HIVAN candidate for kidney transplantation should be counseled for;
– Consent and confidentiality before transplantation,
-Absolute and relative contraindications for kidney transplantation,
-Choice of living versus deceased donor,
-Pre transplant screening and immunization,
-Immunosuppression protocol for induction and maintenance,
-Drug interaction between HAART & CNI,
-Prophylaxis after Transplantation,
–Monitoring after transplantation; Kidney allograft function / HIV viral control,
-Protocol of biopsies in high risk recipient with graft dysfunction post KT,
-Risk of rejection / infection / malignancy post KT,
-Prognosis of HIVAN and chances of recurrence after transplantation,
-Risk of long-term outcomes of renal transplantation in patients with HIVAN,
-Post-transplantation complications; HIV infection of the allograft / Opportunistic infections / Delayed graft function / Retransplantation .
Pros:
(Because availability of c-ART)
-Accept HIV + deceased Donor
–Avoid longer wait-list time and risk of death on dialysis
-Increase kidney donor pool
–Better survival than being on waiting list on dialysis
Cons:
-Risk of rejection , DGF
-Risk of post-transplant infections, malignancy
-Drug interactions between HAART and immunosuppression
-Risk of recurrence of HIVAN post KT
2-Will you elaborate more on HIVAN?
Overview;
-The classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS, although HIVAN may also occur in patients with less advanced HIV infection or following acute seroconversion.
-HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation.
Pathogenesis;
-The pathogenesis of HIVAN is hypothesized to involve direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host.
-The strong associations of HIV with African ancestry and APOL1 gene polymorphisms illustrate the importance of host genetic factors.
Clinical manifestations;
–HIVAN classically presents with heavy proteinuria and a rapid decline in kidney function in a person with advanced HIV disease.
Diagnosis;
-The diagnosis of HIVAN should be suspected in any patient with HIV who presents with nephrotic-range proteinuria and rapidly declining kidney function.
-Our suspicion is particularly high if the patient has a CD4 cell count <200 cells/microL, HIV viremia, and/or has a history of nonadherence to antiretroviral therapy (ART).
-Kidney biopsy is currently the only way to establish a definitive diagnosis of HIVAN.
Histologic diagnosis.
-There are no specific laboratory findings that can be used to distinguish HIVAN from other forms of glomerular disease, including other forms of HIV-associated kidney disease.
-If a kidney biopsy cannot be performed safely, we manage patients with suspected HIVAN similarly as those with biopsy-proven HIVAN.
Treatment;
Approach to the treatment of HIVAN is as follows:
-All patients with HIV infection should receive ART, regardless of CD4 count.
-For patients with HIVAN who are not already receiving ART, ART should be initiated as soon as possible.
-For patients who are already receiving ART, medication adherence should be assessed.
-Patients with HIVAN who have proteinuria and/or hypertension should be treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB).
-This approach is similar to that for patients with proteinuric chronic kidney disease (CKD).
-Patients who have persistent proteinuria in spite of treatment with an ACE inhibitor or ARB may benefit from addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor.
-There is generally no role for routine glucocorticoids in patients with HIVAN.
-In patients whose kidney function is not improving with therapy, the use of glucocorticoids may be considered on a case-by-case basis, weighing the risks of infection and metabolic derangements against the risk of kidney disease progression.
Prognosis;
-The prognosis in patients with HIVAN is poor, even among those treated with ART.
-Many such patients will develop end-stage kidney disease (ESKD).
3-What are the chances of recurrence of HIVAN post-transplantation?
-Insufficient knowledge regarding recurrence of HIVAN but could be in the same way as conventional FSGS, which can be as high as 30% in first grafts
-could be just histological without significant change in the kidney function.
– cART may not have any effect on the recurrence of HIVAN.
-Biopsy, if there is any evidence of Graft dysfunction.
Monitoring Allograft function;
-Biopsy if DGF or graft dysfunction
-(In high risk recipients) follow Protocol biopsies at 1 month, 3 months , and 12 months.
References;
-Rao TK , Filippone EJ , Nicastri AD ,et al: Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome . N Engl J Med 1984;310:669.
-Gardenswartz MH , Lerner CW , Seligson GR , et al: Renal disease in patients with AIDS:a clinicopathologic study . Clin Nephrol 1984; 21:197.
-Winston JA , Bruggeman LA , Ross MD , et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344:1979.
-Levin ML , Palella F , Shah S , et al : HIV-associated nephropathy occurring before HIV antibody seroconversion. Am J Kidney Dis 2001; 37:E39
-DAqati V, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998; 18:406.
-Atta MG , Choi MJ , Longenecker JC , et al.Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. Am J Med 2005; 118:1288.
Thank you, Mohamed Do you mean the risk of recurrence of 30%?
Remember, the FSGS in HIVAN is a secondary FSGS with no chance to recur if the primary cause was treated.
Thanks, our Prof;
I mean: there are insufficient knowledge regarding recurrence of HIVAN and like FSGS in high recurrence rate in first grafts.
Retransplantation in HIVAN
-Patients whose first allograft fails can be considered for retransplantation;
second kidney transplants now comprise 13.1 % of the general waiting list .
One study examined outcomes for 22 patients with HIV who were retransplanted, compared with 4127 HIV-negative matched controls.
Unfortunately, in this analysis, patients with HIV who had a second transplant had a 3.1-fold higher risk of death and a 1.96-fold increased risk of allograft loss.
References;
-Hart A, Smith JM, Skeans MA , et al :OPTN/SRTR 2015 Annual Data Report:Kidney Am J Transplant 2017: 17 Suppl 1:21.
-Shelton BA, Mehta S, Sawinski D, et al: Increased Mortality and Graft Loss With Kidney Retransplantation Among Human Immunodeficiency Virus (HIV)-Infected Recipients.Am J Transplant 2017; 17:173.
Counselling and discussion
According to evidence, a person living with HIV (PWH) should get solid organ transplantation as normal medical care.
The HIV Organ Policy Equity (HOPE) Act also declared that PWH are eligible to become donors.
The recipient must have stable disease for at least the previous six months, have good compliance, viral suppression, CD4 > 200, and be free of opportunistic infections or cancers in order to be eligible for transplantation.
Survival rate is after transplants than hemodialysis.
After transplantation, further care may require close HIV RNA monitoring and immunizations; however, the majority of management is identical to that for non-HIV patients.
Although co-infections with other viruses, such as HCV/HBV, have to be checked out, transplantation remains preferable to dialysis overall despite the increased risk of infections, delayed graft function, and rejection rates.
HIVAN
One of the main factors contributing to CKD and ESKD in black people is HIVAN. Low CD4 count and high viral load are significant risk factors.
CLINICAL FEATRUE
Proteinuria, nephrotic syndrome, renal insufficiency, and hypertension are examples of possible clinical characteristics.
PATHOLOGY AND TREATMENT
Loss of podocytes, abnormal stem cell replenishment, tubular damage, and microcystic tubular dilatation are pathological characteristics.
The majority of treatments are conservative, such as cART, ACEI/ARBS, statins, and in certain situations, a steroid trial.
What are the chances of recurrence of HIVAN post-transplantation
Even in patients with undetectable viral levels who are receiving antiretroviral medication, HIV may still be possible to infect kidney allograft.
High incidence of DGF in recipients with HIV (42.5%) and its detrimental effects on allograft survival (hazard ratio [HR] 1.86, 95% CI] suggest that infections are more likely to be connected to the post-transplant immunosuppressive state than to HIV infection.
Re-transplantation may be explored for patients whose initial allograft fails; second kidney transplants presently account for 13.1% of the overall waiting list.
British Transplantation Society Guidelines
Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy
Sana Waheed,# 1 Ahmad Sakr,# 2 Neha D. Chheda, 3 Gregory M. Lucas, Michelle Estrella, 3 Derek M. Fine, and Mohamed G. Atta
Locke JE, Montgomery RA, Warren DS, et al. Renal transplant in HIV-positive patients: long-term outcomes and risk factors for graft loss. Arch Surg 2009; 144:83.
Malat G, Jindal RM, Mehta K, et al. Kidney donor risk index (KDRI) fails to predict kidney allograft survival in HIV (+) recipients. Transplantation 2014; 98:436.
Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2015 Annual Data Report: Kidney. Am J Transplant 2017; 17 Suppl 1:21.
Thank you, Muhammed
What are the other forms of HIVAN?
Has it been reported in the Caucasian population?
What about the recurrence after transplantation?
In addition to lesions directly linked to intrarenal HIV gene expression, the spectrum of renal pathology in HIV-positive people also includes lesions linked to comorbidities, treatment side effects, immunological dysregulation, and co-infections.
There are four pathologic categories for HIV-related kidney disorders.
HIVAN and immune complex-mediated glomerular disorders are examples of glomerular-dominant nephropathies.
Nephropathies with a tubulointerstitial predominance
HIVAN-related tubulointerstitial damage, acute tubular injury brought on by ART, tubulointerstitial nephritis brought on by medications other than ART, and direct renal parenchymal infection by viral, bacterial, or fungal pathogens
Vascular-dominant nephropathies: thrombotic microangiopathy (reported in the early years of the AIDS epidemic, but now rarely reported) and atherosclerosis
Other nephropathies in the setting of HIV infection: diabetic nephropathy and age-related nephrosclerosis
HIV-associated chronic kidney disease (CKD) varies geographically and depending on the definition used. In North America and Europe, CKD prevalence ranges from 4.7% to 9.7%, with a change in definition to include reduced eGFR and/or proteinuria. In the US, the prevalence of CKD increases to 15.5%.
Insufficient data regarding reoccurrence of HIVAN
Rosenberg AZ, Naicker S, Winkler CA, Kopp JB. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat Rev Nephrol. 2015 Mar. 11 (3):150-60.
Swanepoel CR, Atta MG, D’Agati VD, Estrella MM, Fogo AB, Naicker S, et al. Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018 Mar. 93 (3):545-559.
Diana NE, Naicker S. Update on current management of chronic kidney disease in patients with HIV infection. Int J Nephrol Renovasc Dis. 2016. 9:223-234.
Transplantation in HIV positive patients.
Its considered as safe and of good prognosis comparable to non HIV infected allograft recipients. Selective criteria must be implicated in those patient in order to optimize the safety and minimize adverse outcome . The implication of ART has improved outcome significantly post transplantation .
Minimizing the risk of Activation of HIV post transplantation resulting from immunosuppression status .
Criteria for selection of HIV positive transplant candidate:
1] CD4 of more than 200
2] HIV viral load of less than 50 RNA copies /ml.
3] compliant and adherent to ART medications.
4] No history of active infection such as aspergillosis, active CMV, incomplete treatment of TB.
5] No AIDS -defining illnesses.
HIVN:
Its representing glomerular disease in the form of podocytopathy of either Minimal change disease or classically collapsing FSGS, its commonly encountered in poorly controlled HIV disease with high HIV RNA copies and low CD4 count. Relapse after transplantation is reported anecdotally and there is no consensus about risk of recurrence. Each case must be taken as per its merits. IN general, outcome of transplantation is favorable for HIVN patients
Thank you, Wael
Has it been reported in the Caucasian population?
Q1.
Q2.
Q3.
Source:
-BTS guidelines 2018
-Organ transplantation in persons with HIV by Rebecca N. Kumar and Valentina Stosor
-Oxford handbook of nephrology,2th edition
-Prof, Halawa lecture
Thank you, Ben
What are the other forms of HIVAN?
Has it been reported in the Caucasian population?
You mentioned a recurrence rate of around 30% similar to FSGS, but the FSGS associated with HIV is a secondary one which should not recur if the primary cause was successfully treated
Thnxs prof, yes yes
-University of cape Town classification of HIVAN:
-It is almost exclusive to black adults
-Agree with this statement
Oxford Handbook of Nephrology 2 th edition
Please counsel this patient discussing the pros and cons of transplantation.
Pros:
Cons:
Will you elaborate more on HIVAN?
Introduction
Definition:
Pathophysiology:
Mangement:
What are the chances of recurrence of HIVAN post-transplantation?
Melendez Rivera JG, Hashmi MF. HIV Nephropathy. [Updated 2022 Aug 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Rivera FB, Ansay MF, Golbin JM, Alfonso PG, Mangubat GF, Menghrajani RH, Placino S, Taliño MK, De Luna DV, Cabrera N, Trinidad CN. HIV-associated Nephropathy in 2022. Glomerular Diseases. 2022.
Muller E, Botha FCJ, Barday ZA, Manning K, Chin-Hong P, Stock P. Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies. Transplantation. 2021 Jul 1;105(7):1492-1501. doi: 10.1097/TP.0000000000003485. PMID: 33044431; PMCID: PMC8026768.
BTS guidlines: Kidney & Pancreas Transplantation in Patients with HIV
Thank you, Abhijit
What are the other forms of HIVAN?
You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
What about the recurrence after transplantation? Any evidence?
Pros:
After kidney transplantation, the results of 150 HIV-positive patients were reported in the biggest prospective observational study ever carried out; kidney allograft and patient survival estimate at 1 and 3 years were 90.4 and 73.7 and 94.6 and 88.2%, respectively. Since viral suppression was seen in every patient and their CD4 cell levels were at least 200 cells/ml
Before the transplant, HIV was treated with a combination of ART, and anti-infective prophylaxis was used after the transplant as well.
Control was quite good, and there were just a few instances of opportunistic infections.
cons:
HIV patients had more bacterial infections.
individuals who received ATG or other lymphocyte-depleting agents
PWH also had significant rates of delayed allograft function (hemodialysis in the post-transplant interval), although this did not predict graft failure. Ultimately, HIV-positive kidney transplant patients had allograft rejection rates two to three times greater than the overall kidney transplant group, and rejection predicted allograft failure.
HIVAN can only be diagnosed by kidney biopsy since clinically suspected HIVAN patients frequently have an alternate histologic diagnosis. HIVAN cannot be distinguished from other glomerular diseases, including HIV-associated kidney disease, by laboratory tests. If a kidney biopsy is unsafe, we treat suspected HIVAN like biopsy-proven HIVAN.
Despite ART and adjuvant medications such as renin-angiotensin inhibitors and SGLT2 inhibitors, some HIVAN patients develop ESKD and need dialysis or kidney transplants.
Since the advent of effective ART, HIV-positive dialysis patients have improved survival rates, although mortality remains high. HIV-related dialysis concerns are addressed individually.
HIVAN and ESKD patients may undergo transplantation, however, the allograft may recur. HIV kidney transplantation includes HIV-positive donor organs.
References:
Kumar, R. N., & Stosor, V. (2020). Organ transplantation in persons with HIV. AIDS, 34(8), 1107–1116).
Sawinski D, Forde KA, Locke JE, et al. Race but not Hepatitis C co-infection affects the survival of HIV+ individuals on dialysis in contemporary practice. Kidney Int 2018; 93:706.
Thank you, Isaac
What are the other forms of HIVAN?
You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
What about the recurrence after transplantation? Any evidence?
Certain HIVAN patients may still develop ESKD despite receiving ART and adjuvant drugs such as renin-angiotensin inhibitors and SGLT2 inhibitors. These patients will need either dialysis or a kidney transplant.
Even though there has been significant progress made in the development of effective ART, the overall mortality rate among HIV-positive dialysis patients is still rather high. Concerns with dialysis that are connected to HIV are handled separately.
Transplantation is an option for HIV-AN and ESKD patients; however, there is a chance that the allograft may fail. Transplantation of HIV-infected kidneys requires the use of HIV-positive donor organs.
Please counsel this patient discussing the pros and cons of transplantation.
Pros
· Best modality of RRT compared to PD and HD.
· Better graft and patient survival (at 1 and 3 years 95 and 88 percent allograft survival 90 and 74 percent) compared to other modalities.
· Improve quality of life.
Cons
· Higher risk of allograft rejection
· Increased risk of infections
· Drugs interaction with Immunosuppressant
· Risk of malignancies.
Will you elaborate more on HIVAN?
More common in individual from African descent, presence of APOL1 risk variants is at high risk of HIVAN. Introduction of combination ART has reduced incidence of HIVAN. HIVAN is a major cause of ESKD in people living with HIV. [3] HIV directly infects glomerular and kidney tubular epithelial cells in HIVAN. The strong association between HIVAN and African ancestry indicates that host genetic factors are also important. The mechanism through which variants in APOL1 promote HIVAN and FSGS has not been fully demonstrated. HIVAN usually manifest clinically with;
· Proteinuria usually nephrotic range
· Decline in GFR
· Hypertension and
· Edema
Diagnosis;
Kidney biopsy is required to establish HIVAN
Treatment
The mainstay of treatment is ART along with other supportive therapies
· ART should be initiated as soon as possible in those who are not taking it already; compliance should be assessed in those who are already on ART. Patients who are adherent but increasing viral load should be tested for Drug resistance.
· ACEIs/ARBs
· SGLT2 inhibitors
· Steroids should be considered in HIVIC only.
What are the chances of recurrence of HIVAN post-transplantation?
There is no concrete data to answer this question but inferring from various studies it would be sensible to have closely monitor recipients for;
· Proteinuria
· Viral load
· GFR
· Drugs level and
· Biopsy in order to see for recurrence.
References
1. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients [published correction appears in N Engl J Med. 2011 Mar 17;364(11):1082]. N Engl J Med. 2010;363(21):2004-2014. doi:10.1056/NEJMoa1001197
2. Gathogo E, Harber M, Bhagani S, et al. Impact of Tacrolimus Compared With Cyclosporin on the Incidence of Acute Allograft Rejection in Human Immunodeficiency Virus-Positive Kidney Transplant Recipients. Transplantation. 2016;100(4):871-878. doi:10.1097/TP.0000000000000879
3. Razzak Chaudhary S, Workeneh BT, Montez-Rath ME, Zolopa AR, Klotman PE, Winkelmayer WC. Trends in the outcomes of end-stage renal disease secondary to human immunodeficiency virus-associated nephropathy. Nephrol Dial Transplant. 2015;30(10):1734-1740. doi:10.1093/ndt/gfv207
Please counsel this patient discussing the pros and cons of transplantation.PRO
●RTx is the treatment option for fit patient with life expectancy is >5 years.
●in one study ; patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%.
●Quality of life is better
●Mortality and morbidity and complications of dialysis is higher
CONS
□Renal transplantation in HIV pos patients carries higher risk for acute rejection
□A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively.
□Opportunistic infection remains a major cause of complications and death . (Viral – hepatitis viral- bacterial- TB- …. )
We should discuss the reason of HIVAN
♧ is it delaying of antiviral treatment ?
♡Incompliance for treatment ?
◇Genotyping resistance of viruses ?
This point is very necessary because it may predict the prognosis of graft survival later
Will you elaborate more on HIVAN?●HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS
●Histologically, HIVAN is a collapsing form of (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation
●In individuals of African descent, the presence of APOL1 risk variants have been associated with a higher incidence of HIVAN
●The introduction of combination (ART) substantially reduced the incidence of ESKD attributed to HIVAN
The pathogenesis several factors:
●Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells
●Host factors, including genetic susceptibility
Clinical manifestations
○Nephrotic-range proteinuria
○Rapid decline in kidney function
○Hematuria – 45 to 75 percent
○Hypertension – 12 to 26 percent
○Edema – 22 to 59 percent
Establishing the diagnosis — Kidney biopsy
Initial therapy
●Antiretroviral therapy for all patients
●Additional therapies for proteinuria or hypertension
ACE inhibitors or ARBsSGLT2 inhibitorsWhat are the chances of recurrence of HIVAN post-transplantation?I dont found a study that shows that prevalence of recurrence HIVAN
However, the chances of recurrence of HIVAN depends on
●The compliance with antiviral therapy
●CD 4 less than 200, especially if their CD4 count is less than 50 cells/µ
●the development of acute rejection therefore induction therapy using ATG, rituximab, or plasma- exchange
REFERENCES
Professor Halawa lecture
Kidney & Pancreas Transplantation in Patients with HIV
https://www.nejm.org/doi/full/10.1056/nejmoa1001197
https://emedicine.medscape.com/article/246031-overview#a5
Thank you, Ghalia
What are the other forms of HIVAN?
You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Caucasian population?
Please counsel this patient discussing the pros and cons of transplantation.
Increases quality of life
Decreases mortality
Gold standard treatment for end-stage renal disease
Decreases the cost to the health system
There are drugs with few side effects and effective in viral suppression of HIV
2. Cons
Increased risk of organ rejection
Increased risk of opportunistic infections
Greater need for tests to measure drug interactions
Need for scheduled biopsies to assess graft evolution
Will you elaborate more on HIVAN?
It is a serious manifestation resulting from the high viral load of HIV with significant glomerular damage, especially in the black population, with evolution to collapsing lesions.
There are also kidney injuries resulting from antiretroviral treatment, mainly with Tenofovir and protease inhibitors, but these can be removed and the scheme adapted to drugs that minimize kidney damage.
Proteinuria and metabolic control are essential, but the injury is often irreversible and transplantation is the only alternative for definitive treatment associated with strict viral load control and, consequently, maintaining higher serum CD4 levels.
What are the chances of recurrence of HIVAN post-transplantation?
Yes, there is a high risk, but there is a lack of robust data in the literature to quantify the true relative risk of this situation.
However, without a doubt, the best way to avoid its recurrence is strict viral load control, keeping HIV viral load levels below 50.
In Brazil, we measure the viral load twice a year or in case of clinical intercurrences or laboratory alterations. In special situations, such as a solid organ or bone marrow transplantation, we started measuring every four months.
Antiretroviral regimens with Dolutegravir, an integrase inhibitor, are considered the best, but depending on the sensitivity and clinical context in which the patient is inserted, other drugs may be used with the main objective of maintaining a negative viral load.
Virus genotyping, programmed biopsies, measurement of proteinuria, and serum dosage of immunosuppressants are our main weapons to keep the viral load undetectable.
Thank you, Filipe
What are the other forms of HIVAN? Has it been reported in the Caucasian population?
Glomerular nephropathies
Tubulointerstitial nephropathies
Vascular nephropathies
Diabetic nephropathy
It is less common for Caucasian, but can occur
Please counsel this patient in discussing the pros and cons of transplantation.
Kidney transplantation has been shown to remain the best form of renal replacement therapy, and with proper medical, surgical, and psychological workup, the outcome is usually good. Although CKD patients with HIV used to deny kidney transplantation, that is not the case again as many CKD patients living with HIV have gone through the procedure with a patient and graft survival of 88% and 74% after three years with the advent of use of HAART medications.
The following are the advantages of Kidney transplantation:
The following are the disadvantages of Kidney transplantation:
Elaborate more on HIVAN
HIVAN is the most severe form of CKD, and is the commonest cause of ESRD among those living with HIV. It is known to be very common among black population particularly those living in the West Africa (14.6%) where there has been an association with APOL1 gene mutation form past history of heavy burden of Trypanosomiasis. It is also the third commonest cause of ESRD globally. Although the discovery of HAART has significantly reduces the incidence, but compared to the general population, CKD among HIV patient is four times more
Histologically, it has a similar features to FSGS type of glomerular disease,but for the presence of tubular reticular inclusion within endothelia cell in the HIVAN
What are the chances of recurrence of HIVAN after transplantation
One study examined outcomes for 22 patients with HIV who had another transplantation, compared with over four thousand HIV-negative matched controls.
The patients with HIV who had a second transplant had a 3.1-fold higher risk of death and a 1.96-fold increased risk of allograft loss, hence questioning the utility of the practice.
References
Thank you, isaac
What are the other forms of HIVAN?
You mentioned it is common in the black population with a strong association with APLO 1 gene. Has it been reported in the Cocasian population.
Thank you, prof. for your response
I want to believe the other forms are:
Yes, HIVAN has been reported in Caucasians, although rare compared to African-American with over 90% of cases
Reference
-HIV was traditionally considered an absolute contraindication for renal transplantation, but since the introduction of potent antiretroviral therapy (ART) became widely available , the prognosis of HIV patients was dramatically improved so HIV now is considered a a chronic manageable disease for many patients with well-controlled viral replication .
-Several studies have demonstrated comparable short- and intermediate -term patient and graft outcomes between HIV infected and non infected recipients after introduction of potent ART .
-In patients with HIV and ESKD , RTx has been associated with a survival benefit over dialysis but the risk of Acute rejection and infection was higher in the HIV population .
HIV associated nephropathy :
-HIV associated nephropathy , Collapsing variant of FSGS accompanied by microcystic tubular dilatation and interstitial inflammation
-It’s caused by direct infection of kidney epithelial cells by HIV with subsequent expression of HIV genes in a genetically susceptible host .
-It usually presents with heavy proteinuria and a rapid decline of renal functions with advanced HIV disease .
-Diagnosis is made through clinical suspicion in an HIV +ve patient witha CD4 <200 , HIV viremia or on no ttt .
-Treatments starts by start and adherence to ART , control of HTN and proteinuria (ACEI or , ARBs and SGLT2 may aid as well ) and management of metabolic disorders .
-Prognosis is poor
-There is risk of recurrence of HIVAN after Tx , of unknown rate yet of poor prognosis .
References :
1-Prof.Ahmed Halawa’s lecture
2-Up to date HIV and renal transplantation
Thank you, Dr Mohamed
What are the other forms of HIVAN?
Has it been reported in the Caucasian population?
What about the recurrence after transplantation?