OBJECTIVE:Cyclosporine increases transmembrane calcium flux in mesangial and vascular smooth muscle cells, which may explain cyclosporine-induced decreases in renal bloodflow and glomerular filtration rate. Calcium antagonists, thus, may play a role in the prevention/reversal of cyclosporine nephrotoxicity. DESIGN: In a single-blind, randomized, cross-over study the authors evaluated the effects of a one-week treatment with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on cardiac and renal functions of six stable heart transplant recipients treated chronically withcyclosporine. RESULTS: Both calcium antagonists lowered blood pressure compared with placebo, but only nifedipine increased cardiac output and, therefore, decreased total peripheral resistance significantly more than diltiazem. Nifedipine induced a significant increase in effective renal plasma flow and an insignificant increase in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected by either calcium antagonist to a clinically significant extent. CONCLUSIONS:Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clinical consequences.
RCT Entities:
OBJECTIVE:Cyclosporine increases transmembrane calcium flux in mesangial and vascular smooth muscle cells, which may explain cyclosporine-induced decreases in renal bloodflow and glomerular filtration rate. Calcium antagonists, thus, may play a role in the prevention/reversal of cyclosporinenephrotoxicity. DESIGN: In a single-blind, randomized, cross-over study the authors evaluated the effects of a one-week treatment with nifedipine 20 mg bid, diltiazem 120 mg bid or placebo on cardiac and renal functions of six stable heart transplant recipients treated chronically with cyclosporine. RESULTS: Both calcium antagonists lowered blood pressure compared with placebo, but only nifedipine increased cardiac output and, therefore, decreased total peripheral resistance significantly more than diltiazem. Nifedipine induced a significant increase in effective renal plasma flow and an insignificant increase in glomerular filtration rate, whereas diltiazem caused a reduction in these parameters. Cyclosporine pharmacokinetics were not affected by either calcium antagonist to a clinically significant extent. CONCLUSIONS:Nifedipine and diltiazem exert distinctly different cardiac and renal hemodynamic effects in cardiac transplants, which may have clinical consequences.