Determinants of the glomerular filtration of proteins

We showed previously that a theoretical model treating the glomerular capillary wall as a membrane with uniformly distributed fixed negative charges can account for the observed filtration rates of charged derivatives of dextran in the rat. Using measurements of electrophoretic mobility to estimate effective molecular charge, a necessary input parameter, we present evidence that this model is also consistent with reported filtration rates of several proteins in the rat. Apparent fixed-charge concentrations calculated for serum albumin and three forms of horseradish peroxidase are in the range of 100-130 meq/liter, comparable to the 120-170 meq/liter obtained for charged dextrans. Theoretical effects of hemodynamic changes on filtration of charged macromolecules are considered. With increases in glomerular plasma flow rate (QA) or transcapillary hydraulic pressure difference (delta P), the filtrate-to-plasma concentration ratio (theta) is generally predicted to decrease for neutral or anionic macromolecules but to increase for cationic substances. The more highly charged the macromolecule (cationic or anionic), the more sensitive theta is to such hemodynamic perturbations. For serum albumin, absolute filtration rates are predicted to increase as much as twofold for moderate decreases in QA combined with increases in delta P. Alterations in protein molecular charge offer an attractive explanation for changes in protein filtration during acidosis or alkalosis.