Dialysis Unplugged: Just Say it Ain’t So

My colleague Dr. Sushrut Waikar at the Brigham alerted me to the “Prevention of Serious Adverse Events Following Angiography” (PRESERVE) trial that has been posted on ClinicTrials.gov. The trial is sponsored by the US Department of Veterans Affairs with collaboration from the George Institute. Here’s a 4-arm randomized controlled study targeted to test what therapy best prevents contrast induced nephropathy: hydration versus hydration plus N-acetyl cysteine (NAC) versus bicarbonate alone versus bicarbonate plus NAC.  The investigators are aiming to recruit 8680 subjects with recruitment beginning in July 2012 and completion in 2015.

Wow, what a fantastic study. It will be the largest kidney disease trial funded by tax payers dollars ever – costing hundreds of millions of dollars. Hopefully, it will put to rest the question of what is the best strategy for reducing the risk of contrast-induced nephropathy.

What’s remarkable, however, is that looking through the roster of planned clinical trials from the VA there isn’t a single study on dialysis dose or frequency that is planned. I know we should be celebrating when a large kidney study is funded, but I can't help but ask the question that, if there is money to be allocated on a kidney trial is this the trial one would fund?

Source - Robinson BM and Port FK: CJASN 2009

In other words, is this the most pressing question for our patients with kidney disease? Let alone this broader question, is this the most important issue for VA patients with kidney disease? Is this the best way to spend tax-payers money? Who is setting the priorities?

A much more pressing question is this: Will treating patients with more dialysis result in lower mortality? The Frequent Hemodialysis Network’s Daily Dialysis Trial strongly suggested that frequent in-center dialysis is associated with better outcomes. However, the study has not changed practice and three times a week dialysis is still the standard. It seems a larger study with cleaner primary endpoints is needed. Funding such a study should be, no, must be, a priority for the renal community. In fact it ought to be a priority for the VA and more broadly the government.

Here is what Dr. Julie Ingelfinger, a nephrology colleague at Harvard and NEJM deputy editor said in an NEJM blog after the Frequent Hemodialysis Network’s Daily Dialysis trial was published:  “This randomized trial represents a serious effort to determine the optimal frequency of in-center hemodialysis, but far more data are needed before daily in-center dialysis could become standard of care.  Whether the additional benefits from more frequent dialysis outweigh the potential side effects (particularly those that involve hemodialysis access), the inconvenience, and the added cost remains to be determined.”

Recall that the Frequent Hemodialysis Network’s Daily Dialysis trial was a prospective, multicenter, parallel-group clinical trial randomized 245 dialysis-dependent adults to undergo frequent (6 times per week) or standard (3 times per week) in-center hemodialysis for one year.  Frequent dialysis was significantly superior on both co-primary outcomes: The composite of death or change in left ventricular mass (“death/LVM”; Hazard ratio 0.61, 95%CI 0.46-0.82), as well as the composite of death or change in RAND Physical Health Composite from the SF-36 (“death/PHC”; HR 0.70, 95%CI 0.53-0.92).  Secondary outcomes of hypertension and hyperphosphatemia were also improved, although patients in the frequent hemodialysis arm were more likely to undergo vascular access interventions (HR 1.71, 95%CI 1.08-2.73).

So my plea to the leaders of the Veterans Administration, is “Just Say It Ain’t So”. Please tell me that we’re not going to be foolish enough to spend hundreds of millions of precious clinical trial dollars answering a question on reducing the risk of contrast nephropathy before we prove that more dialysis improves outcomes. Surely not.