Hemodiafiltration and survival of end-stage renal disease patients: the long journey goes on

Survival of end-stage renal disease (ESRD) patients remains unacceptably poor. The excessive mortality of hemodialysis (HD) patients may result, at least in part, from the insufficient removal of medium or high molecular weight uremic toxins and from the systemic inflammatory response induced by the bioincompatibility of HD systems. Hemodiafiltration (HDF) combines diffusion and convection in a single modality, and it appears to be a promising method to improve ESRD patient outcomes. Emerging evidence suggests that this technique may be superior to classic diffusive HD in terms of patient morbidity. Despite the more widespread use of online HDF, evidence for survival benefits of HDF over other treatment modalities is scarce. Results of observational studies suggest lower mortality of HDF patients as compared to HD patients. Recent prospective randomized trials, however, failed to demonstrate any improvement in survival. Subanalyses of these trials, however, showed a significant survival benefit of HDF patients receiving high substitution volumes (17 L per session and more) compared to HD patients and to HDF patients receiving lower volumes. The explanation for this volume-dependent effect remains elusive. There is an urgent need for further randomized controlled trials to confirm previous findings and to identify those ESRD patients that are likely to benefit mostly from HDF.