CALCIUM-ANTAGONISTS IN HEART-TRANSPLANT RECIPIENTS - EFFECTS ON CARDIAC AND RENAL-FUNCTION AND CYCLOSPORINE PHARMACOKINETICS

OBJECTIVE: Cyclosporine increases transmembrane calcium flux in mesang ial and vascular smooth muscle cells, which may explain cyclosporine-i nduced decreases in renal bloodflow and glomerular filtration rate. Ca lcium antagonists, thus, may play a role in the prevention/reversal of cyclosporine nephrotoxicity. DESIGN: In a single-blind, randomized, c ross-over study the authors evaluated the effects of a one-week treatm ent with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on card iac and renal functions of six stable heart transplant recipients trea ted chronically with cyclosporine. RESULTS: Both calcium antagonists l owered blood pressure compared with placebo, but only nifedipine incre ased cardiac output and, therefore, decreased total peripheral resista nce significantly more than diltiazem. Nifedipine induced a significan t increase in effective renal plasma flow and an insignificant increas e in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected b y either calcium antagonist to a clinically significant extent. CONCLU SIONS: Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clin ical consequences.