Model anionic polysaccharide matrices exhibit lower charge selectivity than is normally associated with kidney ultrafiltration

The influence of the anionic polysaccharide matrix (APM) of the glomerular basement membrane (GBM) on water transport and macromolecular transport charge selectivity has been studied in model systems which enable the analysis of the specific properties of the APM. Various APMs were studied including heparin and heparin-like polysaccharides, chondroitin sulfate and dextran sulfate. Upper estimates of the APM concentration in the GBM were obtained by relating measurements of the specific hydraulic conductivity of the heparin-like polysaccharides to measurements of single nephron glomerular filtration rate. This gave values of 40-45 mg ml-1 of polysaccharide, which was then used to analyse factors contributing to macromolecular charge selectivity. Transport analysis of the test dextran probes, used for previous in vivo clearance studies, in APMs demonstrated that there were no differential charge effects at APM concentrations in the range predicted above in the GBM. This was also found to be the case for the partitioning of anionic test probes at the APM-solution interface as measured directly using frontal gel chromatography and through thermodynamic analysis of sedimentation and diffusion data. These studies demonstrated that previous biophysical interpretations of glomerular charge selectivity have severely overestimated the partitioning effect due to the electrostatic effects of polyion-polyion interaction.