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…

2 Replies to “Comment on the latest MDRD article and the state of clinical nephro research”

  1. It could be seen as a linguistic quibble but for me the problem was nicely illustrated when you wrote “artificial barrier between CKD and dialysis”.

    I think the correct way to put this is the artificial barrier between early stage CKD and CKD stage 5. It’s the same disease of course – it’s the severity that changed – and using the CKD stage construct would underscore that there should not be a wall.

    Staying with the CKD stage construct is more precise, with is good in and of itself, but it will also put dialysis in the context of the underlying disease rather then linguistically identifying dialysis as a separate disease, which is too often the case.

    At every CKD stage those who are ill, are managing their CKD. People with stage 5 use dialysis or a transplant to manage their CKD, at stage 3 and 4 we try these other approaches. Turning to your thought experiment I think the dilemma hinges on the patient believing dialysis is another disease and a dread one at that.

    Change the medical bargain – There is a 20% chance you’ll need bypass surgery in five years. Take this course and you might delay the need for surgery for 12 to 18 months but when you have the surgery you’ll be twice as likely to die in the next year.

    I think if the answer is different to both thought experiments then that difference is due to how one perceives dialysis or rather which dialysis one has in mind. I’d want to make sure the person weighing their CKD management options had an accurate understanding of all their renal replacement choices. Fully informed consent. Even with that everyone’s calculus would be different.

    I’m looking forward to your upcoming posts on first year survival after the transition to stage 5.
    Bill Peckham

  2. Bill,

    Send me an e-mail. I’d love to talk.

    I struggled for a while on how I wanted to illustrate the severe feeling of dread I had, the more I thought about the implications of Levey’s article.

    I feel your comment really did a much better. The analogy to CV surgery is perfect. Thanks for your insight.

Comments are closed.