Tag: low-protein diet

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Comment on the latest MDRD article and the state of clinical nephro research

Last Thursday in journal club we reviewed the latest data on protein restriction and progression of CKD.

The best summery of the results are provided at the end of the paper:

…a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, but had no impact on delaying the progression to kidney failure…

Imagine that the primary results had been different. Imagine for a moment that the MDRD study, rather than being one of the first of the large, NIH-sponsored, negative clinical trials in nephrology, was instead a great success. Imagine that the very-low-protein diets resulted in a delay of dialysis of 20% compared to a low protein diet and that a low-protein diet resulted in a 25% delay in progression compared to a normal-protein diet. Imagine a universe where protein restriction is the ACE inhibitors of our universe.

Now imagine if this most recent analysis came out in that universe. The above quote in this imagined universe would read something like:

…a very low-protein diet increased the risk of death in long-term follow-up of the MDRD Study, despite successfully delaying the progression to kidney failure…

How would we as a nephrology community come to terms with the fact that our primary intervention that we were advocating in a thousand CKD clinics across the land, was actually killing our patients after they start dialysis. Imagine the hand wringing as we start to realize that we were able to delay dialysis from 12 months to 18 months but at the cost of a doubling of their first year mortality from 22% to 40%.

I would be horrified and stop advocating it in my clinic but lots of my patients would adopt the low protein strategy, essentially play the lottery that this radical change in diet would allow them to escape their fate.

We as the nephrology community need to demand better research. This study stands alone (nearly? or completely?) by looking at a pre-dialysis intervention but measuring the outcome in dialysis. This study goes over the wall separating chronic kidney disease research from dialysis research. We need a name for this x-ray vision of looking through the artificial barrier between CKD and dialysis. I propose transitional research.

We need to demand that our CKD research does this. This distinction is less important when looking at CKD 3 where only 1% go on to dialysis; but when looking at CKD4 patients we need to know how that intervention affects dialysis survival. In CKD 4, 18% of patients will end up on dialysis in 5 years. (D. Keith’s data, PDF)

Which of today’s avant garde treatment of CKD results in a doubling of dialysis mortality?

  • Use of active vitamin D to treat secondary hyperparathyroidism
  • Treatment of anemia with ESAs
  • Use of phos binders, calcium based or otherwise
  • Bariatric surgery
  • Aggressive control of blood sugar

None of these “standard” therapies has been examined with an eye on total mortality before and after initiation of dialysis. We need the definitive studies so at some time in the future we don’t have to tell a patient’s family that the pills we have been prescribing may actually have caused the stroke or heart attack or cancer or…

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Journal Club: low protein diet

Effect of a very low protein diet on outcome: long-term follow-up.

This is the long-term follow-up of the B group from the original MDRD study.
Enrollment criteria:
  • Age: 18-70
  • Abnormal Cr 1.2-7 women 1.4-7 in men.
  • MAP of 125 or less (160/100)
  • Proteinuria less than 10g per day
  • No diabetics
GFR 13-24 mL/min for the B study (low protein versus very low protein diet). Higher GFR were enrolled in the A study (normal protein versus low protein diet).
Protein was restricted for 3 years.
9 months after the study every nutritional parameter was the same between the two groups.

The primary end-point was a composite of death or dialysis and just about every patient in both groups (95.7%) reached this end-point preventing a separation between the groups (p=0.5). Likewise there was no separation with regards to time to dialysis (p=0.4).

The surprising finding occurs when they looked at death after the initiation of dialysis. There were 34 deaths in the very low-protein group and 19 deaths in the low-protein group (p=0.01).

The separation begins around 15 months and grows over time. This difference was statistically significant and grew to a 2-fold increased risk of death after 6 years.

My take is this fits well with what I tell my patients when they ask me about protein restriction. I have always counseled patients against protein restriction. The two largest RCT were both negative trials (The Modification of Diet in Renal Disease and the Northern Italian Cooperative Study Group). Additionally my patients do not have the benefit of dedicated and repeated nutritional couseling that the patients in these trials receive. My fear is that with little therapeutic upside there is signifigent risk of malnutrition from overzealous protein restriction.

This study probably does not apply to my worry as I doubt patients would adhere to a very low-protein diet.

My other concearn regarding low-protein diets is patients need to get calories from somewhere. Calories can only come from protein, carbohydrates or fat. Considering that the vast majority of CKD patients are destined to die before dialysis I worry that my advice for protein restriction will result in increased carbohydrates (bad for diabetes and possibly CV disease, see Richard Johnson’s fructose hypertension research) and/or increased fats (bad for CV disease) and enhance the risk of death from the more likely outcome.