METHOD OF RENAL MASS REDUCTION IS A CRITICAL MODULATOR OF SUBSEQUENT HYPERTENSION AND GLOMERULAR INJURY

The hypertension, proteinuria, and glomerulosclerosis that develop in the remnant kidney model (uninephrectomy plus infarction of similar to 2/3 Of the other kidney) have been generally considered to represent the adverse consequences of a severe reduction in nephron number. To d ifferentiate the blood pressure (BP) responses to infarction from thos e of reduced renal mass per se, BP was continuously monitored radiotel emetrically in rats whose total renal mass was reduced by 2/3 (infarct ion) and by 5/6 (infarction or surgical excision of both poles) and in sham-operated controls. Hypertension only developed in the two infarc ted groups. Overall averages of systolic BP monitored every 10 min ove r 6 wk were 144 +/- 8 and 156 +/- 5 mm Hg in the 2/3 and 5/6 infarctio n groups (N = 10 each), respectively, as compared with 120 +/- 2 mm Hg (N= 12) in the similar to 5/6 surgical excision group (P < 0.01) and 117 +/- 5 mm Hg (N = 8) in controls. Changes in kidney weights, glomer ular volumes, RBF, GFR, and renal autoregutatory ability after renal m ass reduction by the two methods were qualitatively similar in additio nal animals from each group monitored for 2, 4, or 6 wk without radiot elemetry. Significant proteinuria and glomerulosclerosis only develope d in the two infarction (hypertensive) groups. At 6 wk, 18 +/- 4 and 1 9 +/- 3% of the glomeruli exhibited injury in the 2/3 (N = 22) and the 5/6 infarction groups (N = 21), respectively, in contrast to 3 +/- 1% glomerular injury in the 5/6 surgical excision group (N= 24) (P < 0.0 1). These results demonstrate that a severe reduction in functional re nal mass per se is not responsible for up to 6 wk for the hypertension consistentry observed in the infarction remnant kidney models and fur ther suggest that the adaptive increases in glomerular size and/or fun ction even after severe 5/6 renal mass reduction for up to 6 wk may on ly result in minimal glomerular injury in the absence of hypertension.