Wednesday, January 30, 2013
Sunday, January 27, 2013
Consult Rounds: Zoledronic Acid and Kidney Diseases
- Bisphosphonates, in particular zoledronate(ZA), have been associated with renal toxicity manifested as deterioration in renal function and potential renal failure. Biopsy findings have suggested ATN. Pamidronate on the other hand leads to a more glomerular pathology namely collapsing FSGS.
- In clinical trials, the risk for renal function deterioration was significantly increased in patients receiving ZA infusion over 5 minutes compared with those receiving the same dose over 15 minutes. An abstract presented at ASCO found via an FDA AERS, 480 cases of bisphosphonate-associated acute kidney injury in cancer patients. Patients were mostly female 298 (56%), mean age 66 with most common cancer being myeloma. Associated agents included ZA (n=411, 87.5%), pamidronate (n=8, 17%), and alendronate (n=36, 2%).
- The American Society ofClinical Oncology 2007 Clinical Practice Guideline Update recommends that pamidronate (90mg over no less than 2h) and zoledronate (4mg over 15min) be employed for patients with normal kidney function. In patients with mild-to-moderate kidney disease (estimated CrCl 30-60cc/min), the dose of zoledronate should be reduced with no change in pamidronate, although the committee suggests that clinicians 'consider reducing the initial dose of pamidronate'. For more severe kidney disease (estimated CrCl <30cc/min), zoledronate is not recommended whereas the infusion time for pamidronate should be increased to 4-6h, again with a consideration for reducing the dose. Serum creatinine should be monitored before each dose of bisphosphonate and the drug withheld in patients who develop an otherwise unexplained increase in serum creatinine concentration.
- A case of Fanconi syndrome has also been described in ZA use.
Friday, January 25, 2013
IN the NEWS: Peginesatide for Anemia of Kidney Diseases( PEARLS and EMERALDS)
Anemia treatment in both CKD patients and ESRD patients is challenging. Partial correction is what is recommended at this point. In the past decade, we have seen the rise of erythropoietin and darbopoietin as the major agents used to help manage this condition. Peginesatide was FDA approved in 2012 for use of anemia of kidney disease in dialysis patients. It is a "epomimetic" agents as the authors of the recent four trials published in NEJM suggest. Perhaps a "sensipar" of the anemia world.
Four trails and two manuscripts published in the same issue of Jan 2013 in NEJM this week re the use of this agent in anemia of both ESRD and CKD patients.
Major points:
1. PEARL 1 and 2( use of this agent randomized comparison to darbopoietin) in CKD patients and EMERALD 1 and 2( use of this agent randomized comparison to erythropoietin) in ESRD patients.
2. Both studies showed non inferiority in terms of Hgb control of 10-12 goal as set by the investigators.
3. Cardiovascular end points of MI, Stroke and other cardiac outcomes were similar in both groups in the ESRD study( EMERALD)
4. In the CKD study( PEARL), there were more significant cardiovascular events in the peginesatide arm.
5. AKI and unexplained back pain was also noted more in the CKD group peginesatide arm.
6. Neither the two articles nor the editorial could explain the reason for the increased cardiac events or AKI or back pain with the agent( hgb levels were similar and doses in HD were higher than CKD patients)
7. Benefits of using this agent:- once a month as oppose to more frequent dosing in HD patients
8. Caution: new agent, cost and at this point perhaps not recommended in CKD patients.
When you pubmed the drug name " peginesatide" only 27 articles appear ( 2 are listed above). What do they say regarding this agent? One question that comes up is regarding the clearance, distribution and metabolism of this agent. It seems that pharmcology related studies suggest that this agent is cleared via the kidneys and primarily localized to the hematopoetic sites as concentrations of this agent build up. The molecule is 45kDa molecular weight and low volume of distribution. The mean half-life is 25.0 ± 7.6 hours following intravenous administration and 53.0 ± 17.7 hours following subcutaneous administration in healthy subjects. The mean half-life in dialysis patients is 47.9 ± 16.5 hours following intravenous administration. Mean systemic clearance is 0.5 ± 0.2 mL/hr·kg and mean volume of distribution is 34.9 ± 13.8 mL/kg following intravenous administration in dialysis patients. No accumulation is observed following administration every 4 weeks following intravenous or subcutaneous administration( source: Rxlist.com). The pharmacokinetics of peginesatide in patients with CKD on dialysis are not altered by age, gender or race based on population pharmacokinetic analyses. There is something about dialysis or ESRD that less likely balances out the negative effects of this agent found in CKD patients in terms of cardiovascular mortality.
Four trails and two manuscripts published in the same issue of Jan 2013 in NEJM this week re the use of this agent in anemia of both ESRD and CKD patients.
Major points:
1. PEARL 1 and 2( use of this agent randomized comparison to darbopoietin) in CKD patients and EMERALD 1 and 2( use of this agent randomized comparison to erythropoietin) in ESRD patients.
2. Both studies showed non inferiority in terms of Hgb control of 10-12 goal as set by the investigators.
3. Cardiovascular end points of MI, Stroke and other cardiac outcomes were similar in both groups in the ESRD study( EMERALD)
4. In the CKD study( PEARL), there were more significant cardiovascular events in the peginesatide arm.
5. AKI and unexplained back pain was also noted more in the CKD group peginesatide arm.
6. Neither the two articles nor the editorial could explain the reason for the increased cardiac events or AKI or back pain with the agent( hgb levels were similar and doses in HD were higher than CKD patients)
7. Benefits of using this agent:- once a month as oppose to more frequent dosing in HD patients
8. Caution: new agent, cost and at this point perhaps not recommended in CKD patients.
When you pubmed the drug name " peginesatide" only 27 articles appear ( 2 are listed above). What do they say regarding this agent? One question that comes up is regarding the clearance, distribution and metabolism of this agent. It seems that pharmcology related studies suggest that this agent is cleared via the kidneys and primarily localized to the hematopoetic sites as concentrations of this agent build up. The molecule is 45kDa molecular weight and low volume of distribution. The mean half-life is 25.0 ± 7.6 hours following intravenous administration and 53.0 ± 17.7 hours following subcutaneous administration in healthy subjects. The mean half-life in dialysis patients is 47.9 ± 16.5 hours following intravenous administration. Mean systemic clearance is 0.5 ± 0.2 mL/hr·kg and mean volume of distribution is 34.9 ± 13.8 mL/kg following intravenous administration in dialysis patients. No accumulation is observed following administration every 4 weeks following intravenous or subcutaneous administration( source: Rxlist.com). The pharmacokinetics of peginesatide in patients with CKD on dialysis are not altered by age, gender or race based on population pharmacokinetic analyses. There is something about dialysis or ESRD that less likely balances out the negative effects of this agent found in CKD patients in terms of cardiovascular mortality.
Wednesday, January 23, 2013
New Nephrology Journal with cases to learn from images
The Open Urology and Nephrology Journal(TOUNJ) has an entire section on "Learning from Images"- all open access.
Monday, January 21, 2013
Urine dipstick screening
Early awareness of chronic kidney disease and prevention strategies have led to the mass screening at many places of urine dipstick for albuminuria in the general population. While in diabetics and hypertensives, this might be a very prudent approach, does mass screening really change outcomes? A recent commentary in CJASN discusses the screening concerns from a primary care's perspective. Some key points the authors make are:
1. Based on what a good screening test should be, urine dipstick doesn't cut it. The seven criteria for a good screening test are: target disease is prevalent, morbid; the screening test has to be low risk, cost effective and accurate and acceptable to patients; and we should have the ability to change the outcomes.
2. Many false positives are generate requiring not required follow ups ( especially in a time when we might not have that many nephrologists in near future)
3. Interestingly, are we really changing outcomes. Are we preventing them from getting to ESRD?
This might be a tide changer for many but some points they make are critical to look at. The threshold for screening needs to be higher ( DM, HTN, FMHx, edema - anything that raises the possibility of proteinuria) but as a routine screen for unselected people with no identified risk, the test (which is semi-quantitative and variable at best) probably cause more problems than it solves. Generating inappropriate work up and referrals from a positive dipstick might be interesting to look at closely. Indication is most important in most cases.
1. Based on what a good screening test should be, urine dipstick doesn't cut it. The seven criteria for a good screening test are: target disease is prevalent, morbid; the screening test has to be low risk, cost effective and accurate and acceptable to patients; and we should have the ability to change the outcomes.
2. Many false positives are generate requiring not required follow ups ( especially in a time when we might not have that many nephrologists in near future)
3. Interestingly, are we really changing outcomes. Are we preventing them from getting to ESRD?
This might be a tide changer for many but some points they make are critical to look at. The threshold for screening needs to be higher ( DM, HTN, FMHx, edema - anything that raises the possibility of proteinuria) but as a routine screen for unselected people with no identified risk, the test (which is semi-quantitative and variable at best) probably cause more problems than it solves. Generating inappropriate work up and referrals from a positive dipstick might be interesting to look at closely. Indication is most important in most cases.
Friday, January 18, 2013
International Conference on Glomerular Diseases
We are hosting an international conference on glomerular diseases(ISN and NKF endorsed) as part of our division with exceptional speakers. All interested in learning about the conference and to register, can see the entire brochure online at the listed website of NSLIJ CME. Online registration is offered.
Program of the Day | April 27, 2013 • 7:30 am - 4:00 pm
7:30 am Registration, Continental Breakfast and Exhibitors
8:00 am Welcome and Introduction to Glomerular Diseases
Kenar D. Jhaveri, MD and
Steven Fishbane, MD
8:15 am Minimal Change Disease and FSGS: An Update
Daniel Cattran, MD
8:45 am Clinical Approach to Membranous Nephropathy
Claudio Ponticelli, MD
9:45 am MPGN: The New Classification and Emergence of C3 Nephropathy
Naveed Masani, MD
10:15 am BREAK AND EXHIBITORS
10:30 am HIV Associated Glomerular Diseases
Pravin C. Singhal, MD
11:00 am Treatment of ANCA Associated Vasculitis
Fernando Fervenza, MD, PhD
11:30 am Cancer and Glomerular Diseases
Hitesh H. Shah, MD
12:00 pm LUNCH
1:00 pm Lupus Nephritis: Lessons Learned From Clinical Trials
Richard Furie, MD
1:30 pm Paraproteins and Glomerular Disease
Kenar D. Jhaveri, MD
2:00 pm New Diagnostic Tests and Therapies of IgA Nephropathy
Gerald Appel, MD
2:30 pm Pathology-Based Case Discussion
Glen Markowitz, MD and Panel
4:00 pm Closing Remarks and Adjourn
Kenar D. Jhaveri, MD and Steven Fishbane, MD
An International Update on Glomerular Diseases
Saturday, April 27, 2013
North Shore University Hospital
Rust Auditorium
300 Community Drive
Manhasset, NY 11030
Program of the Day | April 27, 2013 • 7:30 am - 4:00 pm
7:30 am Registration, Continental Breakfast and Exhibitors
8:00 am Welcome and Introduction to Glomerular Diseases
Kenar D. Jhaveri, MD and
Steven Fishbane, MD
8:15 am Minimal Change Disease and FSGS: An Update
Daniel Cattran, MD
8:45 am Clinical Approach to Membranous Nephropathy
Claudio Ponticelli, MD
9:45 am MPGN: The New Classification and Emergence of C3 Nephropathy
Naveed Masani, MD
10:15 am BREAK AND EXHIBITORS
10:30 am HIV Associated Glomerular Diseases
Pravin C. Singhal, MD
11:00 am Treatment of ANCA Associated Vasculitis
Fernando Fervenza, MD, PhD
11:30 am Cancer and Glomerular Diseases
Hitesh H. Shah, MD
12:00 pm LUNCH
1:00 pm Lupus Nephritis: Lessons Learned From Clinical Trials
Richard Furie, MD
1:30 pm Paraproteins and Glomerular Disease
Kenar D. Jhaveri, MD
2:00 pm New Diagnostic Tests and Therapies of IgA Nephropathy
Gerald Appel, MD
2:30 pm Pathology-Based Case Discussion
Glen Markowitz, MD and Panel
4:00 pm Closing Remarks and Adjourn
Kenar D. Jhaveri, MD and Steven Fishbane, MD
Thursday, January 17, 2013
Consult Rounds:Acute Anuria
What is your differential diagnosis when you have anuria?
An article in NEJM in the 1990s mentioned that when there is acute renal injury with anuria, obstruction has to be ruled out. Once that is ruled out, acute cortical necrosis or necrotizing glomerular nephritis are the more likely culprits. An editorial in the same issue by Goodkin et al suggested that acute tubular necrosis and vascular complications should be highly considered in the differential diagnosis. The authors replied back suggesting that ATN should rarely present with no urine output and anuria. Clearly, acute cortical necrosis, obstruction, and renal vein thrombosis( bilateral) in some cases and renal arterial occlusions/tears ( sometimes seen in solitary kidneys and transplant kidneys more) might be causes high on the differential. Severe ATN and AIN have been found to have anuric AKI and perhaps cases of crystalluria as well. PAN as been noted to present such ways as well. Finally, papillary necrosis is another rare finding associated with anuria.
There is an interesting condition called reflex anuria that occurs following certain surgeries. It is defined as cessation of urine output due to irritation of one or both kidneys due to trauma to painful stimuli leading to vasoconstriction. No obvious obstruction is found but ureteric manipulation was done perhaps in pelvic surgery. Its due to arterial vasospasm and ureteral spasm.
In general, Anuric renal disease: think obstruction; vascular catastrophe and cortical necrosis as the three most likely causes.
In general, Anuric renal disease: think obstruction; vascular catastrophe and cortical necrosis as the three most likely causes.
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