Pentosan polysulfate prevents glomerular hypertension and structural injury despite persisting hypertension in 5/6 nephrectomy rats

Five/six nephrectomy induces systemic and glomerular hypertension, glomerul osclerosis, proteinuria, and tubulointerstitial fibrosis. Polysulfate pento san (PPS) decreases mesangial proliferation and extracellular matrix accumu lation. The aim of this study was to determine whether PPS prevents glomeru lar hemodynamic changes and renal damage. Micropuncture studies were perfor med in three groups of eight male Wistar rats. Two groups included rats wit h 5/6 nephrectomy-one of which was treated with PPS in drinking water (100 mg/kg body wt) and the second of which received normal drinking water-and t he third group consisted of normal rats that served as controls. Five/six n ephrectomy produced systemic hypertension, a 50% reduction in GFR, and a 67 % increase in single-nephron GFR due to elevated glomerular pressure and si ngle-nephron plasma flow as well as proteinuria. Hypertension persisted in PPS-treated animals. Despite a similar reduction in GFR, PPS prevented the rise in single-nephron GFR, glomerular capillary hydrostatic pressure, and proteinuria. By morphometry, glomerular volume was increased by 46% and mes angial area by 94%. Fractional glomerular capillary area decreased by 24%. PPS prevented these changes. Tubular dilatation, epithelial cell atrophy, a nd increased interstitial area were largely prevented by PPS, as was the in terstitial inflammatory infiltrate. These results suggest that the renal pr otection conferred by PPS was mediated both by prevention of glomerular hyp ertension as well as suppression of the inflammatory response. It was postu lated that this was partly due to the preservation of a greater fraction of functional nephrons.