Functional and structural correlates of glomerulosclerosis after renal mass reduction in the rat

Previously, it was shown that 5/6 renal mass reduction by surgical excision (RK-NX) results in a marked reduction of glomerulosclerosis (GS) at 6 wk c ompared with the conventional 5/6 renal ablation by infarction (RK-I) model . To determine the pathogenetic correlates of the striking differences in G S, radiotelemetrically measured BP; single nephron function; glomerular vol ume; the temporal expression of mRNA for renin, transforming growth factor- beta, and platelet-derived growth factor-B; and plasma renin concentration were compared between RK-NX, RK-I, and sham-operated control rats. Hyperten sion only developed in the RK-I model, was present at 3 d after infarction, and was correlated with both an increased expression of renin mRNA by Nort hern analysis and elevated plasma renin concentration. Structural (glomerul ar volume) and functional (single nephron blood flow and GFR) indices of th e compensatory adaptive response were significantly but similarly increased in the RK-NX and RK-I rats compared with sham-operated controls, indicatin g that these adaptations per se are not responsible for the initiation of G S after 5/6 renal mass reduction. Glomerular capillary pressure (P-GC) was also significantly increased in both RK-I (56 +/- 2 mmHg) and RK-NX rats (5 0 +/- 0.9 mmHg) compared with controls (46 +/- 0.8 mmHg, P < 0.01), but the increase was significantly greater in RK-I versus RK-NX rats (P < 0.05) co nsistent with the higher BP in RK-I rats. These data indicate that differen ces in renin probably account for the early divergence of BP land P-GC resp onses between RK-I and RK-NX models. Transforming growth factor-beta and pl atelet-derived growth factor-B mRNA expression in pooled RNA from kidneys f rom each group showed increases at 21 d along with early evidence of glomer ular injury in the RK-I group but not in the RK-NX group, consistent with t heir postulated roles as molecular mediators of GS, but only in rats with p athologic glomerular hypertension.