RADIATION NEPHROPATHY IS TREATABLE WITH AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR OR AN ANGIOTENSIN-II TYPE-1 (AT(1)) RECEPTOR ANTAGONIST

Background and purpose: Previous studies showed that progression of es tablished radiation nephropathy could be delayed by continuous treatme nt with high doses of captopril, an angiotensin-converting-enzyme (ACE ) inhibitor. The current studies were designed to determine whether a lower dose or a shorter treatment with captopril would be effective an d whether an angiotensin II type-1 (AT(1)) receptor antagonist (AII bl ocker) would be effective. Materials and methods: In the captopril stu dies, rats were given renal irradiation at doses sufficient to produce radiation nephropathy. Six months after irradiation, animals were str atified by azotemia and assigned to no treatment, continuous high-or l ow-dose captopril, or 6 weeks of high-dose captopril. Captopril was gi ven in drinking water al 62.5 mg/l (low dose) or 500 mg/l (high dose), The AII blocker study had a similar design, except that the nephropat hy was the result of total body irradiation and bone marrow transplant ation and the treatments were no treatment or continuous treatment wit h an AII blocker, L-158,809 (20 mg/l in drinking water). Animals were followed for 1 year with periodic studies of renal function. Results: Survival and renal function were significantly enhanced by all treatme nts. Continuous captopril treatment was more effective than the 6-week course of treatment, but there was no difference in effectiveness bet ween the high and low doses of captopril. In continuous therapy, capto pril and the AII blocker had roughly equivalent efficacy. Conclusions: Both the ACE inhibitor and the AII blocker were effective treatments for established radiation nephropathy. The best results with the ACE i nhibitor required continuous therapy, but could be achieved with a low dose of the drug. (C) 1998 Elsevier Science Ireland Ltd.