ENALAPRIL TREATMENT OF POSTTRANSPLANT ERYTHROCYTOSIS - EFFICACY INDEPENDENT OF CIRCULATING ERYTHROPOIETIN LEVELS

To determine the mechanism of action by which angiotensin-converting e nzyme (ACE) inhibitors lower hematocrit in patients with posttransplan t erythrocytosis, indices of red blood cell production and red blood c ell destruction were obtained serially for 6 months from 10 renal tran splant patients receiving treatment with enalapril for this problem. B efore treatment, five patients had an elevated red blood cell mass, fo ur had plasma volume contraction, and one had both. The mean hemoglobi n concentration decreased by 2 g/dL (range, 0.5 to 3.3 g/dL), from 17 +/- 1 g/dL to 15 +/- 1 g/dL (P = 0.001) following 6 months of enalapri l therapy. Similarly, the mean hematocrit decreased by 8% (range, 3% t o 12%), from 52% +/- 2% to 44% +/- 3% (P = 0.001) during the same peri od. The mean reticulocyte count tended to decrease, although the chang e was not significant. The red blood cell mass decreased dramatically by 15% to 50%, from 32 +/- 9 mL/ld to 23 +/- 4 mL/kg (P = 0.008). Alth ough serial erythropoietin levels declined steadily in two patients, t here was no consistent change in the other patients. Mean levels decre ased modestly, from 20 +/- 11 mU/mL at baseline to 12 +/- 5 mU/mL at 6 months, a change that was not statistically significant. Mean levels at each time point were not statistically different from the mean pret reatment value. Furthermore, during enalapril therapy, there was no co rrelation between mean circulating erythropoietin level and mean hemat ocrit (r = 0.43, P = 0.20) or hemoglobin concentration (r = 0.36, P = 0.30) or between changes in these parameters. Indices of red blood cel l destruction, including haptoglobin, bilirubin, and lactic dehydrogen ase, were unchanged by enalapril therapy, as was calculated plasma vol ume at the beginning and end of the study. The current data suggest th at enalapril improves posttransplant erythrocytosis by impairing red b lood cell production without affecting red blood cell destruction or p lasma volume. Furthermore, hematocrit decreased in most patients witho ut a concomitant decrease in circulating erythropoietin levels. These results suggest that an inhibition of erythropoietin synthesis is not an essential component of the mechanism by which angiotensin-convertin g enzyme inhibitors lower hematocrit in most patients with posttranspl ant erythrocytosis. An inhibitory effect (ie, erythropoietin resistanc e) at the level of the bone marrow appears more likely, a hypothesis t hat would have to be proven by ferrokinetic studies in patients or by direct studies of erythropoiesis in vitro. (C) 1995 by the National Ki dney Foundation, Inc.