How Will the Results of the HEMO Study Impact Dialysis Practice?

Uremia is the clinical consequence of poor renal function and is also the target of hemodialysis (HD) therapy. In the absence of a comprehensive understanding of uremia, the optimum therapy for an average patient with end-stage renal disease (ESRD) can be discovered by observing outcomes during a large clinical trial with randomly assigned dialysis options. The HEMO study was an ambitious effort to bypass traditional studies of disease pathogenesis (uremia) in favorof this typeofpopulation study (1). Themotivation for embarking upon a population study like HEMO has been the persistently high HD mortality rate in the United States over the past 15 years (2). Most clinical trials are tests of drug therapieswhere the primary goal is to determine whether or not the drug in question works, that is, whether treatment with the drug is better than treatment with a placebo. In contrast, the HEMO investigatorswere not hoping for a response, but had true equipoise, meaning that they were equally willing to accept a negative or positive response. In statistical terms, they were equally willing to accept or to reject the null hypothesis, which in this case was that the high dose of dialysis and/or high membrane flux would not have an effect. Potential benefits could be realized with either outcome, so ‘‘failure’’ of such a study only occurs when the outcome is equivocal, perhaps suggesting an effect but with no definite conclusion. The HEMO study results were not equivocal, so the study can be viewed by all participants, patients, investigators, the dialysis industry, and the public in general as a resounding success. The study clearly demonstrated the futility of recent popular attempts to push the dose of dialysis beyond the Dialysis Outcomes Quality Initiative (DOQI) recommendedminimum limit. Prior to the HEMO study, the minimum targeted dose, expressed as a single-pool Kt/V of 1.30 per dialysis treatment administered three times a week, was derived froma consensus of practicing nephrologists (3).Now, in addition to this learned opinion of nephrologists, the HEMO clinical trial provides objective evidence that the previously established minimum dose is also the optimum dose (4). In addition, the HEMO study shows us that improving the clearance of large molecules (independent of small molecules) by using high-flux membranes does not improve the survival of the average patient. Both of these observations have far-reaching implications with regard to the pathogenesis of uremia and its treatment.