Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism.

Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.

Influence of sodium homeostasis on dopaminergic modulation of aldosterone, renin, and prolactin secretion in man.

This study examines the effect of sodium homeostasis on the plasma aldosterone, renin, and PRL responses to the dopamine antagonist metoclopramide in normal individuals. Responses to metoclopramide were evaluated after receiving a 10-meq sodium, 80-meq potassium diet for 5 days and after receiving a 200-meq sodium, 80-meq diet for 5 days. On both occasions, the subjects had reached sodium equilibrium states, as determined by urinary sodium measurements, at the time that they received metoclopramide. Maximum absolute incremental aldosterone responses to metoclopramide were considerably greater (P less than 0.001) in the subjects after 5 days on a 10-meq sodium intake (23.2 +/- 2.0 ng/dl) than after 5 days on a 200-meq sodium intake (6.6 +/-0.9 ng/dl). Greater PRL and PRA responses (P less than 0.05) were also noted with low (10 meq) daily sodium intake, although the influence of sodium intake was less than that observed on the aldosterone response to metoclopramide. PRA responses to metoclopramide occur late (45 min) compared to aldosterone and PRL responses, which were noted 5 min after drug administration, suggesting an indirect effect of dopamine in modulating renin secretion. The proportion of total renin which was inactive was greater with the higher sodium intake. These data suggest that sodium homeostasis may influence dopaminergic modulation of renin, aldosterone, and PRL secretion and may effect the interrelationship between active and inactive renin.