Hemodiafiltration to Address Unmet Medical Needs ESKD Patients

Abstract

Hemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient's blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.

Keywords: Bacteria; Blood Volume; Clinical outcomes; Convection; Dialysis Solutions; Endotoxins; Europe; Filtration; Hemodiafiltration; Humans; Japan; Kidney Failure, Chronic; Kidneys, Artificial; Molecular Weight; Technical requirements; Therapy prescription; hypotension; renal dialysis; ultrafiltration; water-electrolyte balance.

Figure 1.

Dialysate and substitution fluid are prepared using a purification cascade comprising reverse osmosis and two sterilizing ultrafilters. The high-flux dialyzer with polysulfone membranes acts as an additional endotoxin adsorber and provides additional microbial safety.

Figure 2.

Different modalities of hemodiafiltration (HDF) are defined by the route of substitution fluid administration. Q_Bart, arterial blood line to dialyzer; Q_Bven, venous blood line to patient; Q_Di, inlet dialysate flow; Q_Do, outlet dialysate flow; Q_UF, ultrafiltrate flow; Q_Subst, substitution fluid flow.

Figure 3.

The results of a series of clinical trials suggest that patient survival depends on using a high convection volume. (A) Relative survival as a function of convection volume (l/week). (B) Relative survival as a function of convection volume normalized to body surface area (l/week per 1 m²). Reprinted from ref. , with permission.