Effect of Membrane Permeability on Survival of Hemodialysis Patients

Abstract

The biologic plausibility of clinical benefits of high-flux compared with low-flux hemodialysis is supported by observations that numerous molecules with known biologic activities and potentially harmful effects accumulate in the plasma of patients with ESRD and are preferentially cleared by high-flux dialysis. In addition to β2-microglobulin, which is often used as a plasma marker, examples of these toxic middle molecules include parathyroid hormones, advanced glycation products of various molecular weights,1 leptin,2 apolipoprotein C-III,3 and several molecules that inhibit granulocyte functions.4 Empirical support for the clinical benefits of high-flux dialysis is provided by observational studies that report associations of high-flux dialysis with reduced mortality5; however, the Hemodialysis (HEMO) Study, a randomized trial performed in 1846 hemodialysis patients in the United States between 1995 and 2001, failed to demonstrate a decrease in its primary end point of all-cause mortality (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.81 to 1.05) with high-flux compared with low-flux dialysis.6 Nonetheless, because the lower limit of the CI could not rule out an overall hazard reduction of up to 19% and because secondary analyses showed trends favoring high flux for all-cause mortality in patients with >3.7 yr of previous dialysis7 and for cardiac mortality in the full cohort,6,8 …