Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy

Abstract

Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephropathy after BMT. In previous BMT nephropathy studies, ACE inhibitor therapy was started pre-BMT and continued indefinitely. In preparation for clinical trials, studies were designed to determine whether effective prophylaxis could be achieved if ACE inhibitor therapy was started after engraftment, and to determine whether ACE inhibitors needed to be given indefinitely. The present studies in our rat syngeneic BMT model showed that captopril therapy started 25 days post-BMT was as effective as therapy started prior to BMT. When ACE inhibitor therapy was discontinued 28 weeks after BMT, the protective effect was not lost if adequate control of azotemia had been maintained for 26 weeks. If adequate control of azotemia was not maintained for 26 weeks, BMT nephropathy progressed rapidly when ACE inhibitor therapy ended, and slowly when it was continued. Failure to control azotemia was a better predictor of renal failure than failure to control hypertension or proteinuria. Based on these preclinical studies, it would appear that ACE inhibitor therapy will be effective in the prophylaxis of BMT nephropathy even if begun after engraftment, and that ACE inhibitors may not need to be given indefinitely.