Plasma protein adsorption to highly permeable hemodialysis membranes.

Although membrane adsorption of plasma proteins is one of several factors determining the biocompatibility and mass transfer characteristics of a hemodialyzer, this process has not been evaluated rigorously. We performed an equilibrium and kinetic analysis of the binding of proteins of differing molecular weight to highly permeable membranes of differing hydrophobicity and surface change. Hydrophobic, anionic polyacrylonitrile (PAN) and hydrophilic, uncharged cellulose triacetate (CT) membrane fragments were incubated in buffer containing radioiodinated beta 2-microglobulin (beta 2m) or bovine serum albumin (BSA). From an initial solution concentration of 50 mg/liter, both membranes adsorbed significantly more beta 2m than BSA at equilibrium (PAN, 352 +/- 30 vs. 32.1 +/- 2.4 ng; CT, 87.0 +/- 0.6 vs. 30.8 +/- 1.7 ng). These results were consistent with membrane pore exclusion of BSA. Comparison of the slopes of the equilibrium isotherm lines (concentration range, 0 to 220 mg/liter) showed the PAN binding affinity for beta 2m and BSA was 28 and 1.4 times that of CT, respectively. In kinetic studies, the approach to equilibrium versus (time)1/2 was assessed. For all protein-membrane combinations, this relationship was linear, consistent with a diffusion-controlled process. This latter characteristic permitted the determination of beta 2m membrane diffusivity values for both PAN and CT, which were found to be 0.30 and 3.25 x 10(-7) cm2/sec, respectively. These data suggest membrane hydrophobicity more significantly influences the binding of low-molecular weight proteins than that of pore-excluded proteins. In addition, these results demonstrate electrostatic membrane-protein interactions may influence the kinetics of both the adsorption and transmembrane mass transfer of plasma proteins.