Prophylaxis of experimental bone marrow transplant nephropathy.

Renal radiation injury is a known complication of both local kidney irradiation and total body irradiation (TBI). TBI is felt to play an important role in the late-onset chronic renal failure seen after bone marrow transplantation in human beings. Two-hundred and eleven WAG/Rij/MCW rats underwent 0 to 20 Gy TBI followed by syngeneic bone marrow transplant (BMT). Rats received either no drug or verapamil, enalapril, or captopril in the drinking water starting 9 days before TBI and continuing thereafter. Follow-up continued up to 55 weeks after TBI/BMT. No-drug irradiated animals developed significant proteinuria 6 weeks after TBI, were azotemic by 9 weeks after TBI, and were hypertensive by 13 weeks after TBI. Survival was inversely related to the dose of TBI. There was a dose-related reduction in proteinuria, blood pressure, and azotemia with increasing doses of captopril. At 500 mg/L, captopril was more effective than 50 mg/L enalapril in controlling proteinuria, blood pressure, and azotemia and in enhancing survival of irradiated animals. Verapamil, 700 mg/L, did not control proteinuria, blood pressure, or the development of renal failure and did not enhance survival when compared with no-drug irradiated animals. We conclude that angiotensin-converting enzyme inhibitors are beneficial in preventing radiation nephropathy and that control of proteinuria may be of particular importance in preventing progression of renal failure in this model.