Verapamil protects against progression of experimental chronic renal failure

Abstract

Chronic administration of verapamil (Ver) decreases nephrocalcinosis and tubular ultrastructural abnormalities in the remnant model of chronic renal disease. In the present study, the effect of chronic Ver administration on renal function, renal histology and mortality after subtotal nephrectomy was examined. Fourteen days after staged subtotal nephrectomy rats were paired according to renal functional impairment, mean arterial pressure (MAP), and body weight. Rats were pair fed and received either Ver (0.1 micrograms/g sc bid, N = 10) or saline (0.1 ml sc bid, N = 10) for up to 23 weeks. Both members of each pair were sacrificed shortly before the uremic death of controls. At sacrifice, rats treated with Ver had a lower serum creatinine (2.29 vs. 2.99 mg/dl, P less than 0.05) and a higher creatinine clearance (318 vs. 164 microliters/min, P less than 0.05) than controls. In a second experiment, survival was superior in rats treated with Ver than in controls from week seven (P less than 0.0025 by week 14). Serum creatinine was higher at week 10 in control rats (1.68 vs. 1.10 mg/dl, P less than 0.05). MAP was no different between the two groups, irrespective of the time between Ver administration and the measurement of MAP. Histological damage and nephrocalcinosis were worse, and renal and myocardial calcium content was higher in controls. In conclusion, independent of any effect on systematic MAP, chronic administration of Ver protects against renal dysfunction, histological damage, nephrocalcinosis and myocardial calcification, and improves survival in the remnant model of chronic renal disease.