Abstract
The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 ± 5 mm Hg and serum creatinine of 128 ± 9μmol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria.
Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 ± 5 mm Hg compared with 176 ± 7 mm Hg in untreated rats (p > 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 ± 9 μmol/l with enalapril treatment, compared with 159 ± 21 μmol/l (p > 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 ± 3 mg/24 hr vs 85 ± 22 mg/24 hr, p > 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 ± 0.08 vs 2.36 ± 0.16, p > 0.01).
Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125l-hippurate clearance). At 6 wk, filtration fraction was 0.30 ± 0.03 in enalapril treated and 0.48 ± 0.03 in control rats (p > 0.001).
Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function. The intra-renal effect of enalapril may contribute to the preservation of renal structure and function observed.