CHARGE SELECTIVITY OF THE GLOMERULAR-FILTRATION BARRIER IN HEALTHY AND NEPHROTIC HUMANS

We used dextran sulfate (DS) to evaluate barrier charge selectivity in 11 nonproteinuric subjects and in 11 patients with the nephrotic synd rome due to either membranous nephropathy or minimal change nephropath y. The H-3-DS preparation spanned a molecular radius interval of 10-24 angstrom and exhibited size-dependent protein binding in vitro. Urine and ultrafiltrates of plasma were separated by size into narrow fracti ons using gel permeation chromatography. The sieving coefficient (thet a) for ultrafilterable DS of 15angstrom radius averaged 0.68+/-0.03 in nonproteinuric vs. 0.95+/-0.05 in nephrotic subjects (P < 0.001). Unc harged dextrans of broad size distribution were used to evaluate barri er size-selectivity in separate groups of nonproteinuric subjects (n = 19) and nephrotic patients with either minimal change (n = 20) or mem branous nephropathy (n = 27). The value of theta for an uncharged dext ran of similarly small radius (approximately 18angstrom) was significa ntly larger than that observed for DS in nonproteinuric subjects, but was similar in nephrotic individuals. Further, impaired barrier size-s electivity, as assessed by the sieving profile for uncharged dextrans (18-60angstrom radius), failed to account fully for the observed level of albuminuria in almost half of the patients with either minimal cha nge (9/20) or membranous nephropathy (12/27). Together these findings suggest that the human glomerular capillary wall normally provides an electrostatic barrier to filtration of negatively charged macromolecul es such as albumin, and that impairment of this electrostatic barrier contributes to the magnitude of albuminuria in the nephrotic syndrome.