Beta-2 Microglobulin Removal by Immunoextraction and Passive Adsorption in High-Flux Dialyzers

Abstract

The objectives in this study were to compare the removal of 2-M via different dialyzers (high- and low flux) under equilibrium or sink conditions, wherein there was highly selective antibody-based facilitated transport into a small volume dialysate reservoir. Using an in vitro haemodialysis model we perfused high-flux polymethylmethacrylate (PMMA), high-flux cellulose diacetate (CDA), and a low-flux polysulfone (PSF) membranes with known amounts of 2-M through the intracapillary space. Anti-2-M antibodies added to the extracapillary space were shown to create sink conditions across the membrane when its pore size is sufficiently large for diffusion and if 2-M is not strongly adsorbed to the membrane surface. Our results indicate that 2-M (~12kDa) does not penetrate low-flux dialyzers and that its adsorption to intracapillary PSF surfaces does not substantially affect clearance. 2-M strongly adsorbed to high-flux PMMA dialyzers (ko = 0.0271+0.002 min-1), but without significant clearance enhancement due to circulating antibodies. A significant clearance enhancement (101.2%+24.89) for 2-M due to immunoextraction was observed in the high-flux cellulose acetate dialyzers, but without passive adsorption to the surface. These studies demonstrate the utility of in vitro haemodialysis experiments to elucidate midsize molecule clearance in dialysis membranes under controlled conditions. The use of anti-2-M antibodies as dialysate additives might be feasible in the removal of 2-M from whole blood, highlighting the advantages of selective antibody-based extraction of disease-causing toxins into potentially simple extracorporeal devices with small volume receiver compartments.