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.
Cohen
E P
EP
Department of Medicine, Medical College of Wisconsin, Milwaukee.
Moulder
J E
JE
Fish
B L
BL
Hill
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007674:Kidney Diseases / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D011833:Radiation Injuries, Experimental / Q000503:physiopathology; D051381:Rats; D013997:Time Factors; D014511:Uremia / Q000188:drug therapy / Q000503:physiopathology; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use; D014916:Whole-Body Irradiation
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D002216:Captopril; D014700:Verapamil