Perazella M, McPhedran P, Kliger A, Lorber M, Levy E, Bia MJ
Enalapril treatment of post-transplant erythrocytosis: Efficacy independent of circulating erythropoietin levels

Am J Kidney Dis (Sep) 26:495-500 1995

Post-transplant erythrocytosis develops in 9-22% of renal transplant patients generally within the first 2 years. Cyclosporine increases the incidence of erythrocytosis perhaps by inhibiting the production of cytokines which normally inhibit eryhropoiesis. EPO levels produced from the native kidneys are high in only 50% of patients. While anemia is not a complication of ACE inhibitor therapy ACE inhibitor use causes small decreases in HCT in normal subjects but larger (7-25%) decreases in HCT in patients with CRF ESRD or renal transplants. The mechanism of this particular action of ACE inhibitors is unknown.

Perazella et al studied indices of red cell production and survival for 6 months in an unblinded study of 10 renal transplant patients before and during treatment with enalapril (2.5-5 mg/d). They found that enalapril decreased Hb from 17 to 15 gm% HCT from 52 to 44% and produced a significant fall in RBC mass. All patients responded and no patient required phlebotomy once therapy with enalapril was started. There were no changes in indices of plasma volume or RBC survival or EPO levels. RBC production was slightly inhibited (reticulocyte count decreased by 20%). Since RBC mass decreased without changes in RBC destruction or plasma volume the authors conclude that enalapril improves post transplant erythrocytosis perhaps by inhibiting RBC production. Since EPO levels were not altered, inhibition of EPO synthesis is not required, suggesting that enalapril has a direct effect on bone marrow RBC production.

Additional comment. Erythrocytosis has the potential for serious thromboembolic events. The usual therapy is intermittent phlebotomy with discontinuation of diuretics and native nephrectomy in selected patients. Recently medical therapy with theophylline or ACE inhibitors have been proposed. Theophylline is though to work via stimulation of an adenosine-mediated (A2 receptor) decrease in EPO synthesis. The mechanism of action of ACE inhibitors is less clear. This report is the first trial in renal transplant patients. The results show that enalapril is efficacious and works independent of changes in EPO. This study confirms previous reports by Gaston (Transplant Proc 25: 1029- 1031, 1993) and Julian et al (Kidney Int 46: 1397-1403, 1994). The latter study found that withdrawal of enalapril caused erythrocytosis. (Star)

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CRF by problem area : Anemia/Erythropoietin/Iron
H: Drug therapy : ACE inhibitors