Effects of plasma proteins on sieving of tracer macromolecules in glomerular basement membrane

It was found previously that the sieving coefficients of Ficoll and Ficoll sulfate across isolated glomerular basement membrane (GBM) were greatly ele vated when BSA was present at physiological levels, and it was suggested th at most of this increase might have been the result of steric interactions between BSA and the tracers (5). To test this hypothesis, we extended the t heory for the sieving of macromolecular tracers to account for the presence of a second, abundant solute. Increasing the concentration of an abundant solute is predicted to increase the equilibrium partition coefficient of a tracer in a porous or fibrous membrane, thereby increasing the sieving coef ficient. The magnitude of this partitioning effect depends on solute size a nd membrane structure. The osmotic reduction in filtrate velocity caused by an abundant, mostly retained solute will also tend to elevate the tracer s ieving coefficient. The osmotic effect alone explained only about one-third of the observed increase in the sieving coefficients of Ficoll and Ficoll sulfate, whereas the effect of BSA on tracer partitioning was sufficient to account for the remainder. At physiological concentrations, predictions fo r tracer sieving in the presence of BSA were found to be insensitive to the assumed shape of the protein (sphere or prolate spheroid). For protein mix tures, the theoretical effect of 6 g/dl BSA on the partitioning of spherica l tracers was indistinguishable from that of 3 g/dl BSA and 3 g/dl IgG. Thi s suggests that for partitioning and sieving studies in vitro, a good exper imental model for plasma is a BSA solution with a mass concentration matchi ng that of total plasma protein. The effect of plasma proteins on tracer pa rtitioning is expected to influence sieving not only in isolated GBM but al so in intact glomerular capillaries in vivo.