- 82 slides
- Delivered in about 45 minutes
- New in June 2011
- Revised October 2011
- Added data on future agents: Hematide and HIF-stabilizers
- Updated June 2011
- Added CKD data
- included the two RCTs of allopurinol on CKD progression (both positive)
- 121 slides
- Keynote is 96mb, PDF 59mb
- You can do it in an hour, really, you can
- Here is a handout with miniatures of the slides (pdf, 3.8 mb)
I was invited by the Curbsiders to talk about CKD. The discussion went a little long and our discussin got divided into two podcasts, #67 and #69. Here is the second half. I don’t think I made any major mistakes except when discussing combined ACEi and ARB therapy I said ALTITUDE was a study of RAAS inhibtion and endothelin antagonists. Actually ALTITUDE was RAASi and Aliskiren, the direct renin antagonist. And it was stopped not because of hyperkalemia but due to a CV signal (though the combination did have more hyperkalemia). The trial I was thinking about was ASCEND which added the endothelin antagonist avosentin to an ACEi or ARB in patients with diabetic nephropathy. This trial was also stopped early, again for CV issues after only 4 months on the drug!
You can listen to the episode here.
Over the last 16 months, the science has continued to move forward without any hiccups. Additionally, data supporting direct renal toxicity of fructose and uric acid has matured. This latest version of the lecture adds a section on CKD including a summary of both randomized-controlled-trials examining allopurinol to reduce the progression of chronic kidney disease.
The lecture is available in the under the lecture tab.
One of the standard pieces of advice I give patients regarding chronic kidney disease is to avoid NSAIDs. However, not infrequently, patients have co-morbidities that demand NSAIDs. This usually triggers a conversation with my patients where I describe how ibuprofen can cause acute renal failure (I just took care of a new patient who developed RIFLE stage: Failure from a couple of doses of Mobic on top of stepped up ibuprofen use). I then explain that we extrapolate from the acute renal failure that NSAIDs are probably not beneficial in CKD and are likely harmful.
What about chronic renal dysfunction following long-term NSAID intake? In today’s medical environment, the evidence is weak. Prospective cohort studies in the Physicians’ Health Study (Rexrode et al, JAMA 2001) and the Nurses’ Health Study (Curhan et al, Arch Int Med 2004) failed to show an association between even high levels of cumulative lifetime NSAID intake and decrease in renal function.
My concern about these studies is the effect, we physicians have on the outcomes. Telling kidney patients to avoid ibuprofen and other NSAIDs is standard fare in CKD care. I’m sure these patients tend to use less ibuprofen and more acetaminophen, just as liver patients probably do the opposite. So educated patients with CKD will avoid NSAIDs but regardless of NSAID intake they will have a much higher progression to kidney related endpoints than their peers without a diagnosis of CKD. The epidemiologist sees a large cohort of acetaminophen users (my CKD patients) ending up with renal failure and sees that people with CKD use very little ibuprofen and may infere that acetaminophen causes kidney failure and ibuprofen is protective.
These are the type of questions that CRIC should be able to answer.
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:
- They showed less loss of eGFR over 24 months in patients treated with allopurinol. There was actually a modest increase in renal function in the allopurinol group. P=0.016 for eGFR between groups at 24 months.
- They defined renal progression as a loss of more than 0.2 mL/min per month and after using a cox-regression model adjusted for age, gender, diabetes, uric acid, hs-CRP levels, renin-angiotensin system blockers, CKD etiology, and albuminuria they found a hazard ratio of 0.53 (0.28 to 0.99; P=0.048).
A few weeks ago we admitted a patient who has been approaching ESRD for a number of years. Most of her medical care had been provided in the hospital as she bounced from admission to admission. Though we tried to get her into our CKD clinic she always failed to show up. You can track the progression of her CKD from hospitalization to hospitalization with a gradually increasing baseline creatinine.
On this most recent admission, she came in with the triple 8s:
- Hemoglobin 8.8
- Creatinine 8.1
- Potassium 8.6
Here is her initial EKG with that potassium:
The likelihood of renal replacement therapy, either transplant or dialysis, was near zero (≤1.3%) for patients in all stages except stage 4, where 2.3% ± 1.1% of patients received a transplant and 17.6% ± 2.7% had dialysis initiated.
Mr. S., a 38 y.o. African American male, came to the hospital with nausea, vomiting and fatigue. Initial creatinine was 36.2 mg/dl. After hydration overnight it came back at 38 mg/dl.
Update: one of the comments asked about the patients body habitus, rhabdo and BUN.
- Mr S. is muscular but no body builder
- He was not in rhabdo. I would not include an elevated creatinine due to muscle breakdown under the crazy numbers tag as it essentially represents a lab error, in that the creatinine is no longer a measure of severity of the renal failure or the chronicity but rather a measure of the aggregate muscle damage.
- His BUN was 139 mg/dL
This patient had a remote diagnosis of hypertension but had been out of any medications for months. The computer showed a 2 year old creatinine of 2 but the patient denied any memory of being told he had CKD.