TREATMENT OF RADIATION NEPHROPATHY WITH ACE-INHIBITORS

Purpose: A previous study showed that radiation nephritis could be treated with captopril, an angiotensin-converting-enzyme inhibitor. These studies were designed to determine whether other angiotensin-converting-enzyme inhibitors would be effective, whether captopril would inhibit the development of the histopathologic lesions typical of radiation nephritis, and whether captopril could be used to treat the nephropathy observed in bone marrow transplant recipients conditioned with total body irradiation. Methods and Materials: In radiation nephritis studies, rats were given 17-27 Gy bilateral renal irradiation in 5 fractions. Six months after irradiation animals were stratified by blood urea nitrogen and assigned to no treatment, or treatment with captopril (500 mg/l) or enalapril (50 mg/l) in the drinking water. A subset of animals was sacrificed for histopathology after 3 months; the remaining animals 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. Six months after irradiation, animals were stratified by blood urea nitrogen and assigned to no treatment, or treatment with captopril (500 mg/l). Animals remained on drugs for 6 months. In all studies animals were-followed with periodic renal function tests. Results: In the radiation nephritis study, survival and renal function were significantly enhanced by both captopril and enalapril, but there were no significant differences between the drugs. The histopathologic severity of the lesions of radiation nephritis correlated with the degree of renal dysfunction; and in irradiated animals with equal initial azotemia, captopril-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-converting-enzyme inhibitors are an effective treatment for both radiation nephritis and bone marrow transplant nephropathy.