Discuss the link between inflammation and CKD-MBD?
39 Comments
Mahmud ISLAM
Inflammation plays a role in CKD-MBD. This was hypothesized after showing that TNF-α and IL-6 can increase FGF-23 transcription in osteocytes. FGF-23 stimulates the hepatic synthesis of IL-6 and C-reactive protein, leading to ore FGF-23. Some cytokines can induce osteoclast differentiation by increasing bone resorption.
1-close relationship between FGF23 and inflammation ,TNF and IL 6 >>increase FGF23 transcription in osteocytes . 2-FGF23 stimulate the hepatic synthesis of IL 6 and CRP . 3-IDA(either absolute or functional )which stabilize the transcriptional HIF )lead to increase FGF23 . 4-disruption of immune function which occur in CKD might promote bone loss . 5-hyperparathyroidism play a role in the inflammatory state seen in CKD .
The association between inflammation, vascular calcification, and CKDMBD has been extended further. The relation between FGF23 and inflammation found that TNF-α and IL6 can increase FGF23 transcription in the osteocyte, and FGF23 can also stimulate the hepatic synthesis of IL6 and CRP.
Some of the cytokines are capable of inducing osteoclast changing and bone reabsorption
CKD-MBD biochemical and hormonal changes as hyperphosphatemia, hypovitaminosis D, or hyperparathyroid may aggravate the vascular changes with endothelial cell damage and vascular calcification A recent finding TNF-α and IL-6 are capable of increasing FGF-23 transcription in osteocytes FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein (vicious circle) On the other hand CKD FGF-23 cleavage does not occur efficiently and accumulates increasing effect on inflammation Beside some cytokines are able to induce osteoclast differentiation, increasing bone resorption. PTH has role in inflammatory state usually seen in CKD. PTH promotes osteoclast differentiation is complex, involving multiple cell types, and multiple cytokine mediators PTH causes bone resorption by binding to its PTH/PTHrP receptor, expressed in several cell types,including osteoblasts and osteocytes. -T lymphocytes express PTH receptor suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, which amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL) CKD patients experience different iron deficiency, which will stabilize the transcriptional hypoxia inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.in CKD, Considering that HIF stabilizers have been tested for anemia treatment in CKD some are FDA approved, the question that emerges is whether this will increase FGF-23 and worsen CKD-MBD. However, activated immune cells promote bone destruction by stimulating bone resorbing osteoclasts. On the other hand, disruption of immune function, which occurs in CKD patients, might also promote bone loss In summary as theres interaction between the immune system and CKD-MBD, future therapeutic approach may include monitoring for clinical situations that are associated with increased inflammatory status in CKD patients
there is a a vicious circle between inflammatory mediators and FGF-23. some of them increase FGF-23 production which in turn increase hepatic production of inflammatory mediators. stimulated bone cells activates osteoclasts, promoting bone destruction. PTH augment inflammatory status
Thanks Dr. Ahmed. In addition to your answer, disturbed immune system in patients with CKD might induce osteoclastogenesis. Also, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Since the presence of hyperphosphatemia, hypovitaminosis D, or hyperparathyroidism may exacerbate the vascular alterations with endothelial cell destruction and vascular calcification, the relationship between inflammation, vascular calcification, and CKD-MBD has been increased.
TNF- and IL-6’s ability to stimulate FGF-23 transcription in osteocytes revealed the deep relation between FGF-23 and inflammation. Inflammation and FGF-23 production are linked in a vicious circle because FGF-23 increases the synthesis of IL-6 and C-reactive protein in the liver.
Chronic or functional iron deficiency, which is seen in CKD patients, will stabilize the transcriptional hypoxia-inducible factor that stimulates FGF-23 synthesis.
In CKD patients, immune system instability may potentially contribute to bone loss. Patients with primary hyperparathyroidism were shown to have an aggravated inflammatory response.
The inflammatory state typically observed in CKD may potentially be influenced by PTH.
PTH promotes bone resorption via binding to the PTH/PTHrP receptor, which is found in a variety of cell types, including osteoblasts and osteocytes. PTH receptors on T lymphocytes produce enhanced TNF production and osteoclastic activity. PTH stimulates osteoclast differentiation.
-CKD perse is a state of chronic inflammatory state.
-pro-inflammatory cytokines like TNF-alpha and IL-6 can increase FGF-23 transcription in osteocytes.
-FGF-23 is linked to inflammation by stimulation of hepatic synthesis of interleukins 6.
-some cytokines stimulate osteoclast differentiation/ bone resorption.
-PTH plays has a big role in the inflammatory state.
Thanks Dr. Mahmoud. In addition to your answer, disturbed immune system in patients with CKD might induce osteoclastogenesis. Also, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Hyperphosphatemia, hypovitaminosis D, or hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Inflammatory markers like TNF-α and IL-6 can increase FGF-23 transcription in osteocytes. FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein, indicating a vicious circle of inflammation and FGF-23 production. Moreover, some of these cytokines are able to induce osteoclast differentiation, increasing bone resorption.
Anemia in CKD patients whether true and/or functional iron deficiency will stabilize the transcriptional hypoxia- inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.
An increased inflammatory response was described in patients with primary hyperparathyroidism, suggesting that PTH could also play a role in the inflammatory state usually seen in CKD. PTH causes bone resorption by: 1-binding to its PTH/PTHrP receptor, expressed in several cell types, including osteoblasts and osteocytes. 2-Interestingly, T lymphocytes express PTH receptor, suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, a potent inflammatory cytokine that amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL). In an animal model, conditional ablation of PTH receptor in T lymphocytes prevented PTH-induced bone loss confirming the direct effect of PTH on regulating these cells.
Klotho insufficiency or deficiency is also located in the upstream of the CKD–MBD sequence and increases FGF23 synthesis and secretion. In some patients treated with Ca-based phosphate binders and/or VDRAs, serum Ca levels are elevated.
PTH acts on adipose cells and myocytes and increases energy expenditure and muscle atrophy.
Increased Pi and Ca in the circulation lead to the formation and maturation of CPPs. FGF23 can directly induce inflammation via hepatocytes.
CPPs, especially secondary CPPs, can impair the immune system and also induce inflammation via immune cells.
Calcitriol deficiency in CKD is closely linked to impaired immunity, leading to an elevated risk of infection.
Persistent infection causes inflammation, followed by malnutrition.  Malnutrition then accelerates the maturation of CPPs, creating a vicious cycle. Collectively, these results strongly suggest that CKD–MBD causes malnutrition and inflammation, finally leading to sarcopenia and frailty. Notably, malnutrition and inflammation in turn aggravate CKD–MBD.
Ckd MBD can cause inflammation and inflammation can worsen CKD MBD. This is seen as FGF23 causes release of inflammatory mediators and also inflammatory mediators can cause increase FGF23 which is a key component of SHPT. Cytokines could cause bone resorption worsening CKD MBD. Iron deficiency experienced in CKD causes HIF1 stabilisation and that cause increase in FGF23. Are we seeing an effect of inflammation or iron deficiency as a lot of ckd pt have high hepcidin ?
Good job Dr. Muhammad
In addition to you answer, PTH could play a role in inflammation in CKD. Disturbed immune system in CKD might increase bone loss.
Regrading your question, Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability.
There are a relationship between inflammation, vascular calcification and MBD as presence of hyperphosphatemia, vitamin D deficiency and hyperparathyroidism will cause endothelial cells damage and calcification
Close relationships between inflammation ad FGF23 in which the TNF-alpha and IL6 able to increase in FGF23 transcription in osteocyte which in turn stimulate the hepatic synthesis of IL6 and CRP as vicious cycle of inflammation and FGF23 production, some of these cytokines will activate osteoclast and increase bone resorption .
Other factors like iron deficiency anemia in ckd will stabilize the transcriptional hypoxia inducible factor alpha which will stimulate FGF23 production in addition to decrease FGF23 cleavage and will accumulated.
Other factors like Disruption of immune system in ckd also increase bone loss.
PTH also has a role in increasing the osteoclast differentiation through the action on multiple cells like BM stromal cells, osteoblast progenitors, osteoblast and osteocyte and cytokines mediators, PTH causes bone resorption through binding to PTH /PTHrp receptors in many cells like osteoblast and osteocyte.
T lymphocytes also has Receptors of PTH so increasing TNF-alpha which in turn aggrevate osteoclastogenesis and increase bone resorptive activity of the RANKL.
In animals study ablation of PTH receptors in T lymphocytes prevented PTH induced bone loss
there is a strong association between CKD and inflammation which was triggered by hyperphosphatemia ,hypovit d and hyperphosphatemia .This inflamation lead to vascular calcification .
FGF23 increase in inflamation and vice versa and this lead to increase inflamatory marker like TNF and IL 6 which increase FGF23 ,and this in turn will increase the hepatic production from IL6 and CRP.
FGF23 also will increase the cytokines production and this will increase the bone resorbtion .
direct association between the iron deficency anemia and increase of FGF 23 through the HIF which in turn lead to increase bone osteoclast and bone resrbtion .
Disrubtion of immune system which is present in CKD can lead to bone loss.
Metabolic changes and bone disorders cause inflammatory conditions.
FGF-23 by the recent study found close relation between FGF-23 and inflammation, a reversible relation between TNF, IL6 and FGF-23.
TNF and IL6 lead to increase FGF-23, and in reverse FGF-23 stimulate hepatic synthesis of TNF and IL6.
CKD and disturbed immune systems can lead to bone loss.
There was also found by study an association between PTH, and inflammation noticed in primary hyperparathyroidism, ad this is a complex mechanism.
PTH causes bone resorption by binding to its PTH/PTHrP receptor in osteocytes and osteoblasts.
T lymphocytes express the PTH receptor, increasing the synthesis of TNF a potent inflammatory cytokine that intensifies osteoclastogenic and bone resorption.
Controlling of early secondary hyperparathyroidism and preventing parathyroid gland nodularity, may help control inflammatory cascade and prevent bone loss.
A future targeting treatment of CKD-MBD may involve a therapeutic approach to control inflammation, and vascular calcification and by the end of the day prevent cardiac events and improve patient quality of life and survival.
1– Primary HPT increase inflammatory response . 2- increase synthesis of TNF and some inflammatory cytokines that
a- amplifies the osteoclastogenic .
b- resorption activity of the receptor activator of B ligand ( RANKL). activation of immune cells promote bone destruction by stimulating bone resorbing osteoclasts.
Thanks Dr. Ashraf
There is a vicious circle of inflammation and FGF23 production in patients with CKD. Hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
CKD triggers a chronic inflammatory state and chronic iron deficiency anemia.
Chronic inflammatory state:
High synthesis of TNF-alpha and CK-> Increase FGF-23 expression->Increase hepatic synthesis of IL6 an CRP-> Triggers osteoclastic activity and bone resorption
Chronic IDA:
Increase production of HIF-> Increase FGF-23
High FGF-23-> high PTH -> stimulates Lymphocytes -> increases TNF and IL6 production-> increases RANKL-> increases osteoclastic activity and bone resorption
CKD MBD and inflammation
1-close relationship between FGF23 and inflammation ,TNF and IL 6 >>increase FGF23 transcription in osteocytes
2-FGF23 stimulate the hepatic synthesis of IL 6 and CRP
3-IDA(either absolute or functional )which stabilize the transcriptional HIF )lead to increase FGF23
4-disruption of immune function which occur in CKD might promote bone loss
5-hyperparathyroidism play arole in the inflammatory state seen in CKD
1-the presence of hyperphosphatemia, hypovitaminosis D, or hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification .
2-There is strong link between inflammation, vascular calcification, and CKD-MBD .
3-there is a close relationship between FGF-23 and inflammation
4-TNF-α and IL-6 are capable of increasing FGF-23 transcription in osteocyte.
5-FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein, indicating a vicious circle of inflammation and FGF-23 production.
6-some of these cytokines are able to induce osteoclast differentiation, increasing bone resorption.
7-CKD patients experience a chronic true and/or functional iron deficiency, which will stabilize the transcriptional hypoxia- inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.
8-The immune system might actually protect the skeleton Under physiological conditions.
9-activated immune cells promote bone destruction by stimulating bone- resorbing osteoclasts. And disruption of immune function, which occurs in CKD patients, might also promote bone loss .
10-PTH could also play a role in the inflammatory state usually seen in CKD.
11-T lymphocytes express PTH receptor suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, a po- tent inflammatory cytokine that amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL).
12-This interaction between the immune system and CKD-MBD, made a potential future therapeutic approach may include mitigating the effects of and monitoring for clinical situations that are associated with increased inflammatory status in CKD patients.
Discuss the link between inflammation and CKD-MBD?
TNF-alpha and IL-6 are pro-inflammatory cytokines. both can increase FGF-23 transcription in osteocytes.
FGF-23 can stimulate the hepatic synthesis of IL-6 and CRP. therefore, there is a vicious circle of FGF-23 and inflammation.
some cytokines stimulate osteoclast differentiation and therefore increase bone resorption.
CKD is a state of chronic low-grade inflammation and also chronic true and/or functional iron deficiency. iron deficiency will do stabilization of HIF-1 alpha. the latter will increase FGF-23.
T- lymphocytes express PTH receptors and mediate the increasing synthesis of TNF-alpha. the latter has an osteoporotic effect
there were founded close relation between inflammatory process in ckd patients and ckd mbd after demonstrate the level of inflammatory marker like TNF and IL6 there cause stimulation osteocyte to increase level of secretion of FGF23 and that induce increase hepatic synthesis of IL6 and start vicious of inflammation and FGF23 increase activity .also in ckd patients develop 2nd hyperparathyroidism induce more inflammation
some new drug in ttt anemia in ckd cause inflammation like HIF
Thanks Dr. Rabab.
Let me add some points:
Chronic iron deficiency will stabilize HIF1α that stimulates FGF-23 synthesis.
Disturbed immune system in patients with CKD might induce osteoclastogenesis. Hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
PTH could play a role in inflammation in CKD patients.
1. Viscous cycle between inflammatory cytokine that stimulate production of FGF23 and increased level of FGF23 that cause increasing in cytokine level il6 and crp in liver.
2. Those cytokine can increase osteoclast differentiation in bones.
3. Increased level of HIF1alpha& iron deficiency will increase the production of FGF23
4.there is PTH receptor on T lymphocyte which will cause increased secretion of TNF and osteoclastic activity. PTH promote osteoclasts differentiation
Good answer Dr. Ben
In addition to your answer, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
PTH could also play a role in the inflammatory state in CKD.
Physiologically, the immune system may defend the skeleton. Activated immune cells stimulate bone-resorbing osteoclasts. Thus, CKD-related immune dysfunction may cause bone loss.
Patients with primary hyperparathyroidism had a stronger inflammatory response, which suggests that PTH may also contribute to inflammation caused by chronic kidney disease (CKD).
PTH stimulates osteoclast development by interacting with bone marrow stromal cells, osteoblast progenitors, osteoblasts, osteocytes, and various cytokine mediators.
Osteoblasts and osteocytes express PTH/PTHrP receptors, which PTH binds to resorb bone.
T lymphocytes express the PTH receptor, implying that PTH can regulate these cells and increase TNF-, a potent inflammatory cytokine that boosts the osteoclastogenic and bone resorption activities of the receptor activator of nuclear factor B ligand (RANKL).
Osteocytes make more FGF-23 when TNF and IL-6 are present. This suggests that inflammation and FGF-23 are related.
These cytokines may also differentiate osteoclasts, enhancing bone resorption. Chronic iron deficiency and inflammation in CKD patients stabilize HIF1. This boosts FGF-23 production.
In CKD, FGF-23 cleavage fails, and the intact molecule accumulates. HIF stabilizers used to treat anemia caused by CKD raise the question of whether they might also raise FGF-23 and make CKD-MBD worse.
In an animal model, PTH receptor ablation in T lymphocytes reduced PTH-induced bone loss. Given the immune system’s connection with CKD-MBD
Inflammation plays a role in CKD-MBD. This was hypothesized after showing that TNF-α and IL-6 can increase FGF-23 transcription in osteocytes. FGF-23 stimulates the hepatic synthesis of IL-6 and C-reactive protein, leading to ore FGF-23. Some cytokines can induce osteoclast differentiation by increasing bone resorption.
CKD MBD and inflammation ;
1-close relationship between FGF23 and inflammation ,TNF and IL 6 >>increase FGF23 transcription in osteocytes .
2-FGF23 stimulate the hepatic synthesis of IL 6 and CRP .
3-IDA(either absolute or functional )which stabilize the transcriptional HIF )lead to increase FGF23 .
4-disruption of immune function which occur in CKD might promote bone loss .
5-hyperparathyroidism play a role in the inflammatory state seen in CKD .
The association between inflammation, vascular calcification, and CKDMBD has been extended further. The relation between FGF23 and inflammation found that TNF-α and IL6 can increase FGF23 transcription in the osteocyte, and FGF23 can also stimulate the hepatic synthesis of IL6 and CRP.
Some of the cytokines are capable of inducing osteoclast changing and bone reabsorption
CKD-MBD biochemical and hormonal changes as
hyperphosphatemia, hypovitaminosis D, or hyperparathyroid
may aggravate the vascular changes with endothelial cell
damage and vascular calcification
A recent finding TNF-α and IL-6 are capable of increasing FGF-23 transcription in osteocytes FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein (vicious circle)
On the other hand CKD FGF-23 cleavage does not occur efficiently and accumulates increasing effect on inflammation
Beside some cytokines are able to induce osteoclast differentiation, increasing bone resorption.
PTH has role in inflammatory state usually seen in CKD.
PTH promotes osteoclast differentiation is complex, involving multiple cell types, and multiple cytokine mediators
PTH causes bone resorption by binding to its PTH/PTHrP receptor, expressed in several cell types,including osteoblasts and osteocytes.
-T lymphocytes express PTH receptor suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, which amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL)
CKD patients experience different iron deficiency, which will stabilize the transcriptional hypoxia inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.in CKD,
Considering that HIF stabilizers have been tested for anemia treatment in CKD some are FDA approved, the question that emerges is whether this will increase FGF-23 and worsen CKD-MBD.
However, activated immune cells promote bone destruction by stimulating bone resorbing osteoclasts. On the other hand, disruption of immune function, which occurs in CKD patients, might also promote bone loss
In summary as theres interaction between the immune system and CKD-MBD, future therapeutic approach may include monitoring for clinical situations that are associated with increased inflammatory status in CKD patients
there is a a vicious circle between inflammatory mediators and FGF-23. some of them increase FGF-23 production which in turn increase hepatic production of inflammatory mediators. stimulated bone cells activates osteoclasts, promoting bone destruction. PTH augment inflammatory status
Thanks Dr. Ahmed. In addition to your answer, disturbed immune system in patients with CKD might induce osteoclastogenesis. Also, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Great answer. Thanks Dr. Rania
-CKD perse is a state of chronic inflammatory state.
-pro-inflammatory cytokines like TNF-alpha and IL-6 can increase FGF-23 transcription in osteocytes.
-FGF-23 is linked to inflammation by stimulation of hepatic synthesis of interleukins 6.
-some cytokines stimulate osteoclast differentiation/ bone resorption.
-PTH plays has a big role in the inflammatory state.
Thanks Dr. Mahmoud. In addition to your answer, disturbed immune system in patients with CKD might induce osteoclastogenesis. Also, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Hyperphosphatemia, hypovitaminosis D, or hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
Inflammatory markers like TNF-α and IL-6 can increase FGF-23 transcription in osteocytes. FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein, indicating a vicious circle of inflammation and FGF-23 production. Moreover, some of these cytokines are able to induce osteoclast differentiation, increasing bone resorption.
Anemia in CKD patients whether true and/or functional iron deficiency will stabilize the transcriptional hypoxia- inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.
An increased inflammatory response was described in patients with primary hyperparathyroidism, suggesting that PTH could also play a role in the inflammatory state usually seen in CKD.
PTH causes bone resorption by: 1-binding to its PTH/PTHrP receptor, expressed in several cell types, including osteoblasts and osteocytes. 2-Interestingly, T lymphocytes express PTH receptor, suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, a potent inflammatory cytokine that amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL). In an animal model, conditional ablation of PTH receptor in T lymphocytes prevented PTH-induced bone loss confirming the direct effect of PTH on regulating these cells.
Klotho insufficiency or deficiency is also located in the upstream of the CKD–MBD sequence and increases FGF23 synthesis and secretion. In some patients treated with Ca-based phosphate binders and/or VDRAs, serum Ca levels are elevated.
PTH acts on adipose cells and myocytes and increases energy expenditure and muscle atrophy.
Increased Pi and Ca in the circulation lead to the formation and maturation of CPPs. FGF23 can directly induce inflammation via hepatocytes.
CPPs, especially secondary CPPs, can impair the immune system and also induce inflammation via immune cells.
Calcitriol deficiency in CKD is closely linked to impaired immunity, leading to an elevated risk of infection.
Persistent infection causes inflammation, followed by malnutrition.

Malnutrition then accelerates the maturation of CPPs, creating a vicious cycle. Collectively, these results strongly suggest that CKD–MBD causes malnutrition and inflammation, finally leading to sarcopenia and frailty. Notably, malnutrition and inflammation in turn aggravate CKD–MBD.
Well done. Thanks Dr. Alaa
Ckd MBD can cause inflammation and inflammation can worsen CKD MBD. This is seen as FGF23 causes release of inflammatory mediators and also inflammatory mediators can cause increase FGF23 which is a key component of SHPT. Cytokines could cause bone resorption worsening CKD MBD. Iron deficiency experienced in CKD causes HIF1 stabilisation and that cause increase in FGF23. Are we seeing an effect of inflammation or iron deficiency as a lot of ckd pt have high hepcidin ?
Good job Dr. Muhammad
In addition to you answer, PTH could play a role in inflammation in CKD. Disturbed immune system in CKD might increase bone loss.
Regrading your question, Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability.
There are a relationship between inflammation, vascular calcification and MBD as presence of hyperphosphatemia, vitamin D deficiency and hyperparathyroidism will cause endothelial cells damage and calcification
Close relationships between inflammation ad FGF23 in which the TNF-alpha and IL6 able to increase in FGF23 transcription in osteocyte which in turn stimulate the hepatic synthesis of IL6 and CRP as vicious cycle of inflammation and FGF23 production, some of these cytokines will activate osteoclast and increase bone resorption .
Other factors like iron deficiency anemia in ckd will stabilize the transcriptional hypoxia inducible factor alpha which will stimulate FGF23 production in addition to decrease FGF23 cleavage and will accumulated.
Other factors like Disruption of immune system in ckd also increase bone loss.
PTH also has a role in increasing the osteoclast differentiation through the action on multiple cells like BM stromal cells, osteoblast progenitors, osteoblast and osteocyte and cytokines mediators, PTH causes bone resorption through binding to PTH /PTHrp receptors in many cells like osteoblast and osteocyte.
T lymphocytes also has Receptors of PTH so increasing TNF-alpha which in turn aggrevate osteoclastogenesis and increase bone resorptive activity of the RANKL.
In animals study ablation of PTH receptors in T lymphocytes prevented PTH induced bone loss
Good job.
CKD -MBD and the inflamation
there is a strong association between CKD and inflammation which was triggered by hyperphosphatemia ,hypovit d and hyperphosphatemia .This inflamation lead to vascular calcification .
FGF23 increase in inflamation and vice versa and this lead to increase inflamatory marker like TNF and IL 6 which increase FGF23 ,and this in turn will increase the hepatic production from IL6 and CRP.
FGF23 also will increase the cytokines production and this will increase the bone resorbtion .
direct association between the iron deficency anemia and increase of FGF 23 through the HIF which in turn lead to increase bone osteoclast and bone resrbtion .
Disrubtion of immune system which is present in CKD can lead to bone loss.
Good job.
CKD-MBD and Inflammation:
Good answer Dr. Kamal
PTH
1– Primary HPT increase inflammatory response .
2- increase synthesis of TNF and some inflammatory cytokines that
a- amplifies the osteoclastogenic .
b- resorption activity of the receptor activator of B ligand ( RANKL).
activation of immune cells promote bone destruction by stimulating bone resorbing osteoclasts.
Thanks Dr. Ashraf
There is a vicious circle of inflammation and FGF23 production in patients with CKD.
Hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
CKD triggers a chronic inflammatory state and chronic iron deficiency anemia.
Chronic inflammatory state:
High synthesis of TNF-alpha and CK-> Increase FGF-23 expression->Increase hepatic synthesis of IL6 an CRP-> Triggers osteoclastic activity and bone resorption
Chronic IDA:
Increase production of HIF-> Increase FGF-23
High FGF-23-> high PTH -> stimulates Lymphocytes -> increases TNF and IL6 production-> increases RANKL-> increases osteoclastic activity and bone resorption
Well done Dr. Asmaa
CKD MBD and inflammation
1-close relationship between FGF23 and inflammation ,TNF and IL 6 >>increase FGF23 transcription in osteocytes
2-FGF23 stimulate the hepatic synthesis of IL 6 and CRP
3-IDA(either absolute or functional )which stabilize the transcriptional HIF )lead to increase FGF23
4-disruption of immune function which occur in CKD might promote bone loss
5-hyperparathyroidism play arole in the inflammatory state seen in CKD
Good answer. Thanks Dr. Emad
CKD-MBD and Inflammation :
1-the presence of hyperphosphatemia, hypovitaminosis D, or hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification .
2-There is strong link between inflammation, vascular calcification, and CKD-MBD .
3-there is a close relationship between FGF-23 and inflammation
4-TNF-α and IL-6 are capable of increasing FGF-23 transcription in osteocyte.
5-FGF-23, in turn, stimulates the hepatic synthesis of IL-6 and C-reactive protein, indicating a vicious circle of inflammation and FGF-23 production.
6-some of these cytokines are able to induce osteoclast differentiation, increasing bone resorption.
7-CKD patients experience a chronic true and/or functional iron deficiency, which will stabilize the transcriptional hypoxia- inducible factor (HIF1α). This, in turn, stimulates FGF-23 synthesis.
8-The immune system might actually protect the skeleton Under physiological conditions.
9-activated immune cells promote bone destruction by stimulating bone- resorbing osteoclasts. And disruption of immune function, which occurs in CKD patients, might also promote bone loss .
10-PTH could also play a role in the inflammatory state usually seen in CKD.
11-T lymphocytes express PTH receptor suggesting that PTH can also regulate these cells, increasing the synthesis of TNF-α, a po- tent inflammatory cytokine that amplifies the osteoclastogenic and bone resorptive activity of the receptor activator of nuclear factor B ligand (RANKL).
12-This interaction between the immune system and CKD-MBD, made a potential future therapeutic approach may include mitigating the effects of and monitoring for clinical situations that are associated with increased inflammatory status in CKD patients.
Good job Asmaa.
Discuss the link between inflammation and CKD-MBD?
Great answer Dr. Ibrahim
there were founded close relation between inflammatory process in ckd patients and ckd mbd after demonstrate the level of inflammatory marker like TNF and IL6 there cause stimulation osteocyte to increase level of secretion of FGF23 and that induce increase hepatic synthesis of IL6 and start vicious of inflammation and FGF23 increase activity .also in ckd patients develop 2nd hyperparathyroidism induce more inflammation
some new drug in ttt anemia in ckd cause inflammation like HIF
Thanks Dr. Rabab.
Let me add some points:
Chronic iron deficiency will stabilize HIF1α that stimulates FGF-23 synthesis.
Disturbed immune system in patients with CKD might induce osteoclastogenesis.
Hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
PTH could play a role in inflammation in CKD patients.
1. Viscous cycle between inflammatory cytokine that stimulate production of FGF23 and increased level of FGF23 that cause increasing in cytokine level il6 and crp in liver.
2. Those cytokine can increase osteoclast differentiation in bones.
3. Increased level of HIF1alpha& iron deficiency will increase the production of FGF23
4.there is PTH receptor on T lymphocyte which will cause increased secretion of TNF and osteoclastic activity. PTH promote osteoclasts differentiation
Good job Dr. Nour. Also, disrupted immune system in patients with CKD might increase bone loss.
CKD-MBD & inflammation:
There is vicious circlce of inflammation & FGF-23 synthesis
Other mechanisms:
Good answer Dr. Ben
In addition to your answer, hyperphosphatemia, vitamin D deficiency, and hyperparathyroidism may aggravate the vascular changes with endothelial cell damage and vascular calcification.
PTH could also play a role in the inflammatory state in CKD.
Yes, agree you. other factors including oxidative stress, arteriosclerosis, repeated infections, & malnutrition
Physiologically, the immune system may defend the skeleton. Activated immune cells stimulate bone-resorbing osteoclasts. Thus, CKD-related immune dysfunction may cause bone loss.
Patients with primary hyperparathyroidism had a stronger inflammatory response, which suggests that PTH may also contribute to inflammation caused by chronic kidney disease (CKD).
PTH stimulates osteoclast development by interacting with bone marrow stromal cells, osteoblast progenitors, osteoblasts, osteocytes, and various cytokine mediators.
Osteoblasts and osteocytes express PTH/PTHrP receptors, which PTH binds to resorb bone.
T lymphocytes express the PTH receptor, implying that PTH can regulate these cells and increase TNF-, a potent inflammatory cytokine that boosts the osteoclastogenic and bone resorption activities of the receptor activator of nuclear factor B ligand (RANKL).
Osteocytes make more FGF-23 when TNF and IL-6 are present. This suggests that inflammation and FGF-23 are related.
These cytokines may also differentiate osteoclasts, enhancing bone resorption. Chronic iron deficiency and inflammation in CKD patients stabilize HIF1. This boosts FGF-23 production.
In CKD, FGF-23 cleavage fails, and the intact molecule accumulates. HIF stabilizers used to treat anemia caused by CKD raise the question of whether they might also raise FGF-23 and make CKD-MBD worse.
In an animal model, PTH receptor ablation in T lymphocytes reduced PTH-induced bone loss. Given the immune system’s connection with CKD-MBD
Good job Weam.