Je. Moulder et al., NONCONTINUOUS USE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN THE TREATMENT OF EXPERIMENTAL BONE-MARROW TRANSPLANT NEPHROPATHY, Bone marrow transplantation, 19(7), 1997, pp. 729-735
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.