NONCONTINUOUS USE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN THE TREATMENT OF EXPERIMENTAL BONE-MARROW TRANSPLANT NEPHROPATHY

Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephropathy after BMT. In previous BMT ne phropathy studies, ACE inhibitor therapy was started pre-BMT and conti nued indefinitely, In preparation for clinical trials, studies were de signed 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 s tudies in our rat syngeneic BMT model showed that captopril therapy st arted 25 days post-BMT was as effective as therapy started prior to BM T. When ACE inhibitor therapy was discontinued 28 weeks after BMT, the protective effect was not lost if adequate control of azotemia had be en maintained for 26 weeks, If adequate control of azotemia was not ma intained for 26 weeks, BMT nephropathy progressed rapidly when ACE inh ibitor therapy ended, and slowly when it was continued, Failure to con trol azotemia was a better predictor of renal failure than failure to control hypertension or proteinuria. Based on these preclinical studie s, it would appear that ACE inhibitor therapy will be effective in the prophylaxis of BMT nephropathy even if begun after engraftment, and t hat ACE inhibitors may not need to be given indefinitely.