Hemofiltration and Hemodiafiltration

Introduction

Conventional hemodialysis (HD) is based on diffusive transport of solutes across a semipermeable membrane and is effective in removing water-soluble small-molecular-weight (MW) solutes and electrolytes. The removal of solutes with larger molecular sizes, such as phosphate and β ₂ -microglobulin, however, is limited by diffusive resistance. Because insufficient removal of these larger uremic toxins may contribute to the high cardiovascular mortality risk observed in these patients, the need for better removal of those solutes has become evident. It has long been known that larger molecules can be removed across membranes more efficiently by convective transport, which is less size limited than diffusive clearance.

In the 1970s, hemofiltration (HF) was developed as a pure convective therapy, which was later followed by the introduction of hemodiafiltration (HDF), which combines the advantages of diffusion and convection into one therapy. In both HF and HDF, plasma water is filtered across the dialyzer membrane in excess of the ultrafiltration volume (UFV) required to control hydration status. The volume of excessively filtered fluid is replaced into the blood in form of sterile, nonpyrogenic substitution fluid to maintain hemodynamic stability.

Initially, sterile replacement fluid was provided in plastic bags, and for reasons of cost and practicability, the total fluid replacement volume per session was therefore limited. The understanding that sufficient removal of uremic middle-MW substances may be achieved by enhanced convective transport led to the development of on-line production of sterile, nonpyrogenic replacement fluid. With modern on-line HDF (ol-HDF) machines, nearly unlimited volumes of dialysate and substitution fluid can be produced, and therefore, much higher convection and substitution volumes are achieved. Among all intermittent extracorporeal treatment strategies, ol-HDF has the potential to provide the largest removal of the widest range of solutes.

Currently, ol-HDF is used in routine clinical practice for more than 10% of the European dialysis population, with an increasing trend. In northern European countries, more than a quarter of patients and in Switzerland, more than 60% of dialysis patients are treated with ol-HDF. In the United States, ol-HDF was only recently approved by the Food and Drug Administration but is currently used only rarely.

Definitions

In hemofiltration , water, and solutes from the blood compartment are driven by positive hydrostatic pressure across a semipermeable membrane into the filtrate compartment, from where it is drained. With the flow of water, small and large solutes get dragged through the membrane at a similar rate (solvent drag effect). Dialysate is not used in HF.

Hemodiafiltration is defined by the European Dialysis (EUDIAL) working group as extracorporeal blood clearance treatment that combines diffusive and convective transport using a high-flux dialyzer with ultrafiltration (UF) coefficient > 20 mL/mm Hg/h/m ² , a sieving coefficient for ß2-microglobulin > 0.6, and a percentage of effective convective transport > 20% of the total processed blood.

Convection volume ( CV ) is defined as the achieved total UFV, the sum of the replacement volume, and the intradialystic weight loss obtained over an entire HDF session.

Preparation of Ultrapure Replacement Fluid: Technical Issues

Water used for convection-based therapies needs to fulfill very stringent criteria of chemical and microbial purity, which has led to the concept of “ultrapure water,” which means virtually sterile and nonpyrogenic. The basic technical setup includes pretreatment of regular community drinking water by microfiltration, activated charcoal, and downstream microfiltration, followed by two reverse-osmosis modules in series. Such ultrapurified water is delivered to dialysis machines, and ultrapure dialysate is produced by “cold sterilization” of freshly prepared regular dialysis solution using additional sterilizing ultrafilters. Finally, replacement fluid is generated online by filtering ultrapure dialysate through bacteria- and endotoxin-retentive filters to prepare a sterile and nonpyrogenic solution that can be immediately infused into the patient ( Fig. 12.1 ).

Modes of Hemodiafiltration

Modes of HDF are defined by the site in relation to the dialyzer, where replacement fluid is infused into the patient's blood.

Postdilution Hemodiafiltration

This is the most common form of ol-HDF worldwide and the HDF mode best studied in randomized controlled trials (RCTs). In the postdilution mode, replacement fluid is infused downstream of the dialyzer, usually into the venous bubble trap ( Fig. 12.2 A). The concentration of filtered substances in the ultrafiltrate depends on the sieving coefficient for each compound. For solutes with a sieving coefficient of 1, which can pass the membrane unimpeded, the concentration in the ultrafiltrate will be identical to the plasma water concentration. Because UF is enforced on undiluted blood, hemoconcentration occurs within the blood compartment of the dialyzer. Postdilution HDF is the most efficient mode in terms of increasing solute removal.