Drugs in Osteoporosis in CKD: Orson Moe, MD
1. Anti reabsorptive agents: Kill osteoclasts
Bisphosphanates: work fast, blasts slow down and increase bone quantity but turnover is reduced ( so not a good option for someone with Adynamic bone disease). Usually contraindicated in GFR<30. If you have CKD stage 3 and you have a low DEXA and aydnamic bone disease and get a bisphosphanate, now hyou have zero turnover more fractures.
HRT/SERM: inhibit osteoclast proliferation and function, again leading to low turnover
Calcitonin: doesn’t completely kill osteoclast, the balance of blasts is maintained. Not widely used though.
Anti RANKL M ab: data on CKD lacking and transplant no experience
2. Osteo anabolic agents
Pth: pulse pth, data on CKD not very strong
Strontium, IGF-1 and other s in pipeline
Best agents in CKD: Calcicum, Vitamin D, Exercise and dietary acid lowering.
Saturday, November 20, 2010
ASN Live Update 2010; CKD -BMD or Osteoporosis
Is it Osteoporosis or CKD-BMD? Miller Brent,MD
1. Fractures in CKD can be caused by CKD-BMD and osteoporosis
2. Clinical risk factors in CKD: chronic heparin use, hypoganadism, steroid exposure, increase prolactin, poor nutrition, Vitamin D def, secondary pth
3. KDIQO guidelines for osteoporosis in CKD-BMD
Stage 1-3 low bone mass or fracture noticed, more likely osteoporosis related than CKD-BMD
Stage IV-V bone biopsy might be necessary to differentiate
4. If bone specific Alk Phos is elevated, you can rule out osteoporosis, and adynamic bone disease as long Paget and malignancy has been ruled out
5. An elevated Pth ( 6 normal) excludes adynamic bone disease
6. A normal alkaline phosphatase, and normal to low pth cannot rule out adynamic bone disease
7. Gold standard would be Bone biopsy
8. Is osteoporosis and CKD-BMD overalap, or is osteoporosis a part of CKD-BMD or is CKD-BMD a type of osteoporosis is not clear?
1. Fractures in CKD can be caused by CKD-BMD and osteoporosis
2. Clinical risk factors in CKD: chronic heparin use, hypoganadism, steroid exposure, increase prolactin, poor nutrition, Vitamin D def, secondary pth
3. KDIQO guidelines for osteoporosis in CKD-BMD
Stage 1-3 low bone mass or fracture noticed, more likely osteoporosis related than CKD-BMD
Stage IV-V bone biopsy might be necessary to differentiate
4. If bone specific Alk Phos is elevated, you can rule out osteoporosis, and adynamic bone disease as long Paget and malignancy has been ruled out
5. An elevated Pth ( 6 normal) excludes adynamic bone disease
6. A normal alkaline phosphatase, and normal to low pth cannot rule out adynamic bone disease
7. Gold standard would be Bone biopsy
8. Is osteoporosis and CKD-BMD overalap, or is osteoporosis a part of CKD-BMD or is CKD-BMD a type of osteoporosis is not clear?
ASN Live Update 2010: Osteoporosis, steroid induced and CKD
Bones and Nephrologists
Steroid related Osteoporosis , Mary Leonard , MD
Take Home Points
1. Steroid induced osteoporosis is 2nd most common cause of osteoporosis
2. Steroids uncouple bone formation and reabsorption
3. They increase osteoclast apoptosis
4. Besides other known risk factors, kidney associated risk factors are microalbuminuria and proteinuria, medications like CNI.
5. Vitamin D is albumin bound and in nephritic syndrome, there is Vitamin D loss. Usually in NS, the 250H levels are low, this is temporary as pth levels don’t really rise as much based on studies compared to true Vitamin D deficiency.
6. FRAX program online is a good tool to assess risk for fractures. Age, gender, BMI, prior fracture, smoking and other factors are all entertained.
7. Recent ACR 2010 guidelines say that Steroid induced osteoporosis can be divided into three categories based on FRAX scores, <10% low risk, 10-20% is mod risk and rest high risk.
8. Bisphosphanates work best for steroid induced osteoporosis. Data on Forteo is new and can be better than bisphosphanates.
Steroid related Osteoporosis , Mary Leonard , MD
Take Home Points
1. Steroid induced osteoporosis is 2nd most common cause of osteoporosis
2. Steroids uncouple bone formation and reabsorption
3. They increase osteoclast apoptosis
4. Besides other known risk factors, kidney associated risk factors are microalbuminuria and proteinuria, medications like CNI.
5. Vitamin D is albumin bound and in nephritic syndrome, there is Vitamin D loss. Usually in NS, the 250H levels are low, this is temporary as pth levels don’t really rise as much based on studies compared to true Vitamin D deficiency.
6. FRAX program online is a good tool to assess risk for fractures. Age, gender, BMI, prior fracture, smoking and other factors are all entertained.
7. Recent ACR 2010 guidelines say that Steroid induced osteoporosis can be divided into three categories based on FRAX scores, <10% low risk, 10-20% is mod risk and rest high risk.
8. Bisphosphanates work best for steroid induced osteoporosis. Data on Forteo is new and can be better than bisphosphanates.
ASN Live Update 2010; Is fibrosis harmful? in the intact nephron?
At the plenary session at ASN 2010, Dr. Kriz discussed about fibrosis and is that really harmful to the intact nephron? studies showed that it is not! at least in the early stages.
The key points are
1. Progressive renal failure is based on the progressive loss of nephrons and they all loose nephrons independently.
2. Fibrosis is an advanced stage that has an autonomous drestruction of so far unaffected nephron remains an open question
The key points are
1. Progressive renal failure is based on the progressive loss of nephrons and they all loose nephrons independently.
2. Fibrosis is an advanced stage that has an autonomous drestruction of so far unaffected nephron remains an open question
ASN Live Update 2010: Glomerular Damage leading to IFTA? How?
A nice plenary session at ASN 2010 by Dr. William Kriz discussed the ways glomerular damage leads to Tubular interstitial damage?
Two theories exist: Leak theory and loss of albumin and other proteins can be damaging to the tubules
Data on this theory not that great.
second theory: As glomruli get damaged, eventually the damage gets closer to glomuler tubular juunction and that leads to spreading of misdirected filtrate and cell proliferation and that leads to intra tubular obstruction and degeneration of tubules.
Leads to IFTA in glomerular disease...
Interesting concepts and worth exploring more on this...
Two theories exist: Leak theory and loss of albumin and other proteins can be damaging to the tubules
Data on this theory not that great.
second theory: As glomruli get damaged, eventually the damage gets closer to glomuler tubular juunction and that leads to spreading of misdirected filtrate and cell proliferation and that leads to intra tubular obstruction and degeneration of tubules.
Leads to IFTA in glomerular disease...
Interesting concepts and worth exploring more on this...
Friday, November 19, 2010
ASN Live Update 2010: VEGF and Diabetic Nephropathy
The VEGF and Diabetic Nephropathy
Take home points from Fuad Ziyadeh lecture
1. Glucose, glycosalation, ROS, TGF B and Ang II all increase VEGF –A ( in podocyte) and lead to proteinuria.
2. Two new players that might be interesting are Notch 1 and Mir 93 in this concept
3. Two mechanisms of albuminuria are paracrine and autocrine effects. Paracrine meaning effecting the receptor of the VEGF ad autocrine meaning affect the VEGF directly
4. Paracrine: increase glucose, ROS and ang II lead to endothelial NOS and VEGF expression and then vascular injury
5. Autocrine effects: a decrease in nephrin and nephrin is in the podocytes hence leading to an autocrine effects
6. A recent paper referenced below showed that VEGF was activated in many human GNs
7. Early in DM – you get increase VEGF, later on there is loss of podocytes and hence a decrease in VEGF. So using VEGF inhibitors can lead to bad outcomes as well and sclerosis.
reference:
http://www.ncbi.nlm.nih.gov/pubmed/20395257
Take home points from Fuad Ziyadeh lecture
1. Glucose, glycosalation, ROS, TGF B and Ang II all increase VEGF –A ( in podocyte) and lead to proteinuria.
2. Two new players that might be interesting are Notch 1 and Mir 93 in this concept
3. Two mechanisms of albuminuria are paracrine and autocrine effects. Paracrine meaning effecting the receptor of the VEGF ad autocrine meaning affect the VEGF directly
4. Paracrine: increase glucose, ROS and ang II lead to endothelial NOS and VEGF expression and then vascular injury
5. Autocrine effects: a decrease in nephrin and nephrin is in the podocytes hence leading to an autocrine effects
6. A recent paper referenced below showed that VEGF was activated in many human GNs
7. Early in DM – you get increase VEGF, later on there is loss of podocytes and hence a decrease in VEGF. So using VEGF inhibitors can lead to bad outcomes as well and sclerosis.
reference:
http://www.ncbi.nlm.nih.gov/pubmed/20395257
ASN Live Update 2010: VEGF and the podocyte
Podocyte and VEGF
Few take home points from Dr. Susan Quaggin Lecture
1. Local VEGF is important for glomerular development
2.VEGF and VEGF R-2 signal against the flow of urine
3. Modulation of VEGF is important.
4. When you remove VEGF in mice, you get TMA , but when you remove the VEGF-R , no TMA
5. If all VEGF-R2 receptors are removed from entire body endothelial cells, showed TMA in all of the kidney. The liver showed endothelial damage and nodular liver as well
Few take home points from Dr. Susan Quaggin Lecture
1. Local VEGF is important for glomerular development
2.VEGF and VEGF R-2 signal against the flow of urine
3. Modulation of VEGF is important.
4. When you remove VEGF in mice, you get TMA , but when you remove the VEGF-R , no TMA
5. If all VEGF-R2 receptors are removed from entire body endothelial cells, showed TMA in all of the kidney. The liver showed endothelial damage and nodular liver as well
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