musings of a salt whisperer
Kenar Jhaveri, MD, (Kidney 007), assistant professor of medicine at Hofstra Medical School and contributor to Nephron Power, is doing a survey on nephrology education. Go take the survey.
I don’t want to spoil the survey but it mentions two resources I was not familiar with:
In my grand rounds on uric acid’s link to renal disease and hypertension I was not able to show any compelling data that allopurinol actually helped adults. There is convincing data on the use of allopurinol for the treatment of adolescent hypertension. The only adult data I could find was a VA study which used a retrospecitve electronic chart review to show that patients prescribed allopurinol had a lower risk of death. Pretty weak sauce.
Now we have more compelling data showing a reduction in the progression of CKD thanks to Goicoechea et al.
The primary objective of this study was to analyze the effect of allopurinol in patients with moderate CKD in reduction of inflammatory markers and renal disease progression.
But I couldn’t find a specific case definition of renal progression in Materials and Methods. In the results they showed significant reduction in renal disease progression by two means:
UPDATE: please see this post with newer, more definitive data.
Initial patient visits for autosomal dominant polycystic kidney disease are different from just about any other patient visits. It is the only disease in which I spend a significant amount of time discussing the areas of bleeding edge research that have promise but are not yet available. I tell my patients about three current research thrusts:
Polycystic kidney disease cells show abnormal activation of the Ser/Thr kinase target of of rapamycin. This enzyme coordinates cell growth and proliferation. In three animal models of PKD, there is evidence of inappropriate activation of mTOR in the renal cysts. Because of this, blocking mTOR with rapamycin (same thing as sirolimus) is one of the most promising research avenues in ADPKD. In this latest study by Perica et al. they had 21 patients and they received either conventional therapy or sirolimus (initial dose: 3 mg daily) for six months and then each patient crossed over to the opposite arm, so every patient received both control and experimental therapy. Six patients dropped out for various reasons and the researchers ultimatly reduced their target sirolimus levels from 10-15 ng/ml to 5-10 ng/ml. The authors explained the adverse reactions in the discussion:
Three patients were prematurely withdrawn from the study because of the onset of an erythema nodosus in one case and thrombocytopenia in two cases after a few days of sirolimus therapy, when sirolimus dosage was titrated to target trough levels between 10 and 15 ng/ml (all events fully resolved with treatment withdrawal). The poor tolerability of this high-dosage regimen led us to reduce the target levels to 5 to 10 ng/ml. With this approach, no serious event requiring treatment interruption was observed.
The primary outcome was change in the kidney volume. The authors, additionally, looked at changes in cyst volume and renal parenchymal volume which was important as they found an increase in the renal parenchyma with stable cyst volume during sirolimus and a reduction in renal parenchyma and increase in cyst volume during usual care.
The primary outcome, a change in renal volume was not significant, P=0.45; however, cyst volume increased more on conventional therapy, P=0.013 and parenchymal volume increased more on sirolimus, P=0.005.
Hypercholesterolemia is another widely known adverse effect of mTOR inhibitors. Our data, however, show that in patients without concomitant medications that may also ad- versely affect the lipid profile, such as steroids or calcineurin inhibitors, hypercholesterolemia is mild and can be easily managed just with dietary counseling. Thus, this adverse effect does not seem to be a major drawback of sirolimus therapy, even in the case of prolonged exposure.
English: A plaque reminding of the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island), near Rano Kau. The plaque is written in Brazilian Portuguese, and reads: In this location were obtained, in January 1965, soil samples that allowed for the obtainment of rapamycin, a substance that inaugurated a new era for organ transplant patients. An homage from the Brazilian investigators, November 2000.
The St. John Hospital and Medical Center has a nephrology fellowship where I am on the teaching staff. We currently have a particularly talented cohort of fellows but I had no idea how that talented compared on a national scale.
We just got the results of the Nephrology In-Service exam and our crew hit it out of the park. The average score was 69, only 4 programs (with five or more fellows) scored higher. Congratulations guys!
One of the major advancements in nephrology in the first decade of the 21ast century was the rejection of Kt/V as a treatment target in dialysis. In a field that is lacking in randomized clinical trials we had three well done randomized clinical trials designed to verify the mounds of observational data. In all three Kt/V as an expression of dose failed.
Chronic hemodialysis: HEMO
Dialytic support for acute renal failure: VA/NIH ATN trial
What lessons does home hemo have to teach acute renal failure in the ICU? What lessons does it have for peritoneal dialysis. One could argue that one of the central problems in modern dialysis is fluid management. Too many of my patients are chronically fluid overloaded leading to hypertension and over worked hearts. Home hemo corrects hypertension. Is solving that cardiovascular problem accounting for much of the improved clinical outcomes?
Don’t let your patients get volume overloaded
The study is a retrospective interpretation of registry data on children with acute renal failure receiving continuous renal replacement therapy. Each patient was given a fluid overload score by calculating a percentage overload:
They divided patients into three strata:
Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a 3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.
6:59 pm: Walt asks if Apple knew it would build a tablet before it built the iPhone.
Jobs: “I’ll tell you a secret. It began with the tablet. Jobs first charged his staff with developing a tablet, but after seeing their first efforts decided the way to go was a phone. “My God, I said, this would make a great phone … so we shelved the tablet and built the iPhone.”
About a month ago, Nephron Power wrote about a great electrolyte case in AJKD. The case regarded a patient who drank a liter of methanol but was asymptomatic. The reason the patient was apparently resistant to a toxic methanol slug of methanol (The quantity of methanol that produces toxicity ranges from 15 to 500 ml of a 40% solution to 60 to 600 ml of pure methanol) was protective powers of abacavir. Abacavir is a nucleoside reverse transcriptase inhibitor and apparently, is a potant inhibitor of alcohol dehydrogenase, the critical enzyme which converts methanol into formaldehyde. Formaldehyde is then converted into the lethal formic acid by formaldehyde dehydrogenase.
After reading this I started to wonder if abacavir was such an effective inhibitor of alcohol dehydrogenase what happens when patients get exposed to say a more common substrate of alcohol dehydrogenase such as whiskey. Shouldn’t we hear about people on abacavir going on alcohol benders after a single shot of ethanol?
A couple of cracks at PubMed and I sure didn’t find much. Barber, Marrett et al. looked for two types of alcohol reactions from abacavir, either a disulfaram-like reaction or reduced alcohol tolerance. The authors found three cases of in 173 patients starting abacavir. They found one disulfarem reaction (nausea, tachycardia, flushing with a single shock of vodka) and two cases of decreased alcohol tolerance
After three glasses of wine he felt as though he had a bottle and a half, with memory loss.
The only other paper I could find was by McDowell, Chittick, et al. who looked at increased abacavir levels with alcohol intake. The reverse of what I was looking for, but at least it was related. They gave a single dose of abacavir and 0.7 g/kg of ethyl alcohol to 25 HIV positive men. They found a 26% increase in the half life of abacavir with alcohol but…
This study did not demonstrate any alteration in the pharmacokinetic parameters of ethanol by abacavir coadministration; blood ethanol median profiles following ethanol administration in the presence and absence of abacavir were essentially superimposable. There was no evidence that co-administration of abacavir interferes with ethanol metabolism. There were no disulfiram-type reactions in any subject who received coadministration of abacavir and ethanol.
This study tested the effects of a single dose of abacavir, chronic dosing may result in a different effect on alcohol dehydrogenase.
Interesting case nonetheless.
Not everyday that you get a new review of a ten year old book. Thanks Beaver Medic.
