TREATMENT OF RADIATION NEPHROPATHY WITH ACE-INHIBITORS

Purpose: A previous study showed that radiation nephritis could be tre ated with captopril, an angiotensin-converting-enzyme inhibitor. These studies were designed to determine whether other angiotensin-converti ng-enzyme inhibitors would be effective, whether captopril would inhib it the development of the histopathologic lesions typical of radiation nephritis, and whether captopril could be used to treat the nephropat hy observed in bone marrow transplant recipients conditioned with tota l body irradiation. Methods and Materials: In radiation nephritis stud ies, rats were given 17-27 Gy bilateral renal irradiation in 5 fractio ns. Six months after irradiation animals were stratified by blood urea nitrogen and assigned to no treatment, or treatment with captopril (5 00 mg/l) or enalapril (50 mg/l) in the drinking water. A subset of ani mals was sacrificed for histopathology after 3 months; the remaining a nimals continued on drugs for 7 months. In the bone marrow transplant nephropathy study, rats received 14-17 Gy total body irradiation in 6 fractions over 3 days followed by syngeneic bone marrow transplant. Si x months after irradiation, animals were stratified by blood urea nitr ogen and assigned to no treatment, or treatment with captopril (500 mg /l). Animals remained on drugs for 6 months. In all studies animals we re-followed with periodic renal function tests. Results: In the radiat ion nephritis study, survival and renal function were significantly en hanced by both captopril and enalapril, but there were no significant differences between the drugs. The histopathologic severity of the les ions of radiation nephritis correlated with the degree of renal dysfun ction; and in irradiated animals with equal initial azotemia, captopri l-treated rats developed less severe renal lesions. Finally, captopril also prolonged survival and preserved renal function in this rat bone marrow transplant nephropathy model. Conclusion: Angiotensin-converti ng-enzyme inhibitors are an effective treatment for both radiation nep hritis and bone marrow transplant nephropathy.