DETERMINANTS OF GLOMERULAR HYPOFILTRATION IN NEPHROTIC PATIENTS WITH MINIMAL CHANGE NEPHROPATHY

Physiologic and morphologic techniques were used to eluciate the deter minants of the GFR in 25 nephrotic patients with minimal change nephro pathy. They were divided into two groups according to the finding of e ither a normal (Group 1, N = 13) or a depressed (Group 2, N = 12) inul in clearance. RPF, afferent oncotic pressure, and dextran sieving coef ficients were determined. Mathematical models of glomerular ultrafiltr ation were then used to compute likely upper bounds for the ultrafiltr ation coefficient and pore area/length ratio (a measure of pore densit y). The upper bounds for each measure of intrinsic ultrafiltration cap acity 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 patien ts with minimal change nephropathy. A corresponding excess of ultrafil tration pressure (versus control), attributable solely to reduced intr acapillary oncotic pressure, was by 10.8 and 11.5 mm Hg, respectively. Glomerular morphometry revealed peripheral capillary filtration surfa ce area to be preserved in both minimal change nephropathy groups. How ever, a significant reduction in filtration slit frequency due to epit helial podocyte broadening correlated with the computed ultrafiltratio n 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 m inimal change nephropathy but that an offsetting reduction in intracap illary oncotic pressure prevents the GFR from declining in many cases. However, the models presented here predict that the depression of cap illary oncotic pressure is insufficient to compensate when the ultrafi ltration coefficient is lowered by substantially more than half and th at it is in this circumstance that minimal change nephropathy is most likely to be accompanied by glomerular hypofiltration.