PROTEINURIA AND IMPAIRED GLOMERULAR PERMSELECTIVITY IN UNINEPHRECTOMIZED FAWN-HOODED RATS

Previous studies of glomerular permselectivity have indicated that bot h size selectivity and charge selectivity changes play a role in the p athogenesis of proteinuria. In this study, we measured Ficoll sieving coefficients, hemodynamic parameters, and urinary protein excretion ra tes in the FHH strain of fawn-hooded rats. These animals spontaneously develop systemic and glomerular hypertension, proteinuria, and focal and segmental glomerulosclerosis at a relatively young age. Three grou ps of FHH rats were studied: two-kidney controls (2K), untreated unine phrectomized rats (CON-NX), and uninephrectomized rats treated with th e angiotensin I converting enzyme inhibitor enalapril (ENA-NX). CON-NX rats had higher glomerular transcapillary pressures (($$$) over bar D elta P) and higher urinary excretion rates of both total protein (UpV) and albumin (UaV) than did 2K rats, whereas treatment with enalapril prevented both glomerular hypertension and the increased proteinuria. Ficoll sieving coefficients were significantly higher in both groups o f NX rats compared with 2K rats only for Stokes-Einstein radii (r(s)) greater than or equal to 46 Angstrom. Fits of sieving data to pore mod els showed a small increase in the number of large, nonselective pores in NX, which was not prevented by enalapril treatment. Total clearanc es of Ficoll with r(s) = 36 Angstrom (the size of albumin) in CON-NX a nd ENA-NX groups were unchanged compared with 2K animals. In contrast, UaV in CON-NX rats was more than six times that of 2K and ENA-NX rats . Across groups, UpV, UaV, and the ratio (UaV)/(UpV) all correlated st rongly with ($$$) over bar Delta P. The change in pore-size distributi on did not significantly contribute to the rise in UaV; therefore, the primary cause of albuminuria appears to have been a reduction in the charge barrier to macromolecular filtration. These findings suggest th at increased albuminuria in NX fawn-hooded rats results from a specifi c defect in glomerular charge selectivity, rather than size selectivit y, induced by chronic glomerular hypertension and that enalapril ameli orates albuminuria by preserving glomerular charge selectivity.