Determinants of glomerular hypofiltration in nephrotic patients with minimal change nephropathy

Physiologic and morphologic techniques were used to elucidate the determinants of the GFR in 25 nephrotic patients with minimal change nephropathy. They were divided into two groups according to the finding of either a normal (Group 1, N = 13) or a depressed (Group 2, N = 12) inulin clearance. RPF, afferent oncotic pressure, and dextran sieving coefficients were determined. Mathematical models of glomerular ultrafiltration were then used to compute likely upper bounds for the ultrafiltration coefficient and pore area/length ratio (a measure of pore density). The upper bounds for each measure of intrinsic ultrafiltration capacity were depressed below estimated normal values in healthy controls by 55 and 47% in Group 1 patients and by 86 and 83% in Group 2 patients with minimal change nephropathy. A corresponding excess of ultrafiltration pressure (versus control), attributable solely to reduced intracapillary oncotic pressure, was by 10.8 and 11.5 mm Hg, respectively. Glomerular morphometry revealed peripheral capillary filtration surface area to be preserved in both minimal change nephropathy groups. However, a significant reduction in filtration slit frequency due to epithelial podocyte broadening correlated with the computed ultrafiltration coefficient across the two minimal change nephropathy groups (r = 0.65; P < 0.001). It was concluded that podocyte deformation invariably lowers the ultrafiltration coefficient and pore area/length ratio in minimal change nephropathy but that an offsetting reduction in intracapillary oncotic pressure prevents the GFR from declining in many cases. However, the models presented here predict that the depression of capillary oncotic pressure is insufficient to compensate when the ultrafiltration coefficient is lowered by substantially more than half and that it is in this circumstance that minimal change nephropathy is most likely to be accompanied by glomerular hypofiltration.