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.
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