The renal functional defect of postobstructive nephyropathy. The effects of bilateral ureteral obstruction in the rat.

This study was designed to examine the pathogenesis of the excretory defect produced by bilateral ureteral obstruction in the rat. After release of obstruction of 24 hr duration glomerular filtration rate was reduced to 20% of normal. Free flow proximal tubular pressure was normal, excluding residual obstruction as a cause of depressed filtration, and indicating that an intrarenal hemodynamic abnormality was primarily responsible for the excretory defect. Total renal blood flow and cortical distribution of flow were normal. Clearance and micropuncture studies indicated the presence of marked heterogeneity of nephron function with residual excretory function residing primarily in vasodilated nephrons in which decreased postglomerular arteriolar resistance effected a reduction in glomerular filtration pressure. Heterogeneity of nephron function was evidenced by a wide scatter of values for single nephron filtration rate and from direct intratubular injection of dye which revealed that at least 28% of surface nephrons were either nonfiltering or had filtration rates too low to measure. The observed decrease in Hippuran extraction and increased ratio of Hippuran to inulin clearance ratio is characteristic of the vasodilated kidney. Further evidence of the vasodilated nature of residual functioning nephrons was demonstrated by the failure of intrarenal papaverine infusion to increase filtration rate in this lesion. The hemodynamic defect produced by bilateral obstruction is contrasted with that seen after release of unilateral ureteral ligation in which depression of filtration rate appears to result primarily from preglomerular vasoconstriction. This difference raises the possibility that a vasodilating substance accumulates during total suppression of renal excretory function. Diuresis and natriuresis were constant features of the postobstructive lesion. The present data support previously published studies which localize the defect in sodium transport to the distal nephron and indicate that this defect is a consequence of increased intraluminal pressure and tubular dilatation induced by bilateral ureteral ligation.