The biophysical basis of hypofiltration in nephrotic humans with membranous nephropathy

Physiologic and morphologic techniques were used to elucidate the determinants of the glomerular filtration rate in 62 nephrotic patients with membranous nephropathy and 104 healthy controls. Renal plasma flow, glomerular filtration rate, afferent oncotic pressure and dextran sieving coefficients were determined. Mathematical models of glomerular filtration were then used to compute likely upper bounds for the ultrafiltration coefficient and pore area/length ratio (a measure of pore density). These upper bounds for each measure of intrinsic ultrafiltration capacity were both depressed by 75% in membranous nephropathy. A corresponding excess of ultrafiltration pressure (versus control), attributable solely to reduced intracapillary oncotic pressure was by 12 mm Hg. Glomerular morphometry revealed peripheral capillary filtration surface area to be enhanced in membranous nephropathy (3.27 x 10(5) vs. 2.03 x 10(5) micron2). However, there was a massive reduction in filtration slit frequency due to epithelial podocyte broadening (336 vs. 1204 slits/mm capillary length) as well as marked thickening of the glomerular basement membrane (1130 vs. 388 nm). We conclude that the latter two findings lower the ultrafiltration coefficient in membranous nephropathy by depressing the hydraulic permeability of the glomerular capillary wall. We propose that this abnormality is solely responsible for the hypofiltration observed in a majority of patients with this disease.