ANEMIA IN RENAL-TRANSPLANT RECIPIENTS CAUSED BY CONCOMITANT THERAPY WITH AZATHIOPRINE AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

Immunosuppression of recipients of renal transplants with azathioprine has been associated with two major side effects: hepatotoxicity and m yelotoxicity, mainly in the form of leukopenia. Reports of isolated an emia in these patients have been rare. We now observed the development of severe anemia in 9 out of 11 renal transplant recipients whose imm unosuppressive regimen was converted from cyclosporine plus prednisone to azathioprine plus prednisone. A significant (P=0.001) drop in hema tocrit (from 34+/-4% to 27+/-3%, mean +/- SD) and hemoglobin (from 11. 6+/-1.3 g/dl to 9.5+/-1.0 g/dl) was found. Since a common variable of all these patients was their use of an angiotensin-converting enzyme ( ACE) inhibitor as antihypertensive medication, we speculated that the combination of azathioprine and ACE blocker might be the reason for th e anemia. We then compared 2 groups of 10 patients each who had been o n azathioprine as their regular immunosuppressive agent and who did or did not take an ACE inhibitor. Hematocrit and hemoglobin were signifi cantly (P=0.01) lower in the group of patients taking ACE inhibitors ( 33+/-6% versus 41+/-5% and 11.5+/-2.0 g/dl versus 14.0+/-1.6 g/dI, res pectively). Haptoglobin levels were also significantly (P=0.05) lower in the ACE inhibitor group (116+/-65 mg/dl versus 210+/-114 mg/dl). Er ythropoietin concentration in the serum and the reticulocyte index wer e slightly, but not significantly, higher in the ACE inhibitor group b ut the values were probably too low for their degree of anemia. Compar ing hematological parameters of the patients in the ACE inhibitor grou p before and after beginning of the antihypertensive treatment confirm ed a significant reduction of hematocrit and hemoglobin following ther apy with an ACE inhibitor. Hematocrit fell from 41+/-7% to 36+/-6% and hemoglobin from 14.0+/-2.3 g/dl to 11.3+/-1.5 g/dl (P<0.05 for both). We conclude that the combination of these two drugs should probably b e avoided.