STRUCTURAL BASIS FOR REDUCED GLOMERULAR-FILTRATION CAPACITY IN NEPHROTIC HUMANS

Previous studies have established that in a variety of human glomerulo pathies the reduced glomerular filtration rate (GFR) is due to a marke d lowering of the ultrafiltration coefficient (K-f). To identify the f actors which lower Kf, we measured the filtering surface area per glom erulus, filtration slit frequency, basement membrane thickness, and GF R and its determinants in patients with minimal change and membranous nephropathies and in age-matched healthy controls. Overall values of K -f, for the two kidneys were calculated from GFR, renal plasma flow ra te, systemic colloid osmotic pressure, and three assumed values for th e transcapillary pressure difference. ''Experimental'' values of the g lomerular hydraulic permeability (k(exp)) were then calculated from K- f, glomerular filtering surface area, and estimates of the total numbe r of nephrons of the two kidneys. Independent estimates of the glomeru lar hydraulic permeability (k(model)) were obtained using a recent mat hematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Indivi dual values of basement membrane thickness and filtration slit frequen cy were used as inputs in this model. The results indicate that the re ductions of K-f in both nephropathies can be attributed entirely to re duced glomerular hydraulic permeability. The mean values of k(exp) and k(model) were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement be tween k(exp) and k(model) for any given group of subjects. It was show n that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basem ent membrane thickness. The decrease in filtration slit frequency obse rved in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability.