AN IMPROVED GLOMERULAR-FILTRATION RATE IN CARDIAC TRANSPLANT RECIPIENTS WITH ONCE-A-DAY CYCLOSPORINE DOSING

We tested the hypothesis that there would be a difference in the unwan ted side effects of cyclosporine (CsA) when heart transplant patients received CsA once a day versus half the dose twice a day, Eight stable cardiac transplant patients (>6 months posttransplant) were administe red their dose of CsA either as a once-a-day dose or half the dose b.i .d. for 21 days in a random fashion, After 21 days the patients were c rossed over to the other regimen, Patients underwent inulin and PAH cl earances at CsA trough on each arm of the study, Each patient collecte d several 24-hr urines for determination of creatinine clearance, and had ambulatory blood pressure monitoring done during each arm of the s tudy, Serum chemistries and lipid profiles were performed at the end o f each arm of the study, The CsA dose was 1.9-7.2 mg/kg/day. All patie nts were hypertensive and on calcium channel antagonists, Once-a-day C sA dosing resulted in a 29% decrease in trough CsA levels, A significa nt increase in glomerular filtration rate, as estimated by the clearan ce of inulin, (65.16+/-24.4 q. day vs. 54.62+/-19.0 b.i.d. (ml/min) P< .02) and a significant increase in renal plasma flow, as estimated by the clearance of PAH, occurred with once-a-day dosing when compared wi th b.i.d. dosing (P=.02). Creatinine clearances were not different bet ween the 2 arms of the study and significantly overestimated glomerula r filtration rates (P=.01). CsA dosing b.i.d. resulted in significantl y higher nocturnal blood pressures (91.2+/-8.3 b.i.d. vs. 86.4+/-8.1 q . day, mmHg, P=.015) when compared with once-a-day dosing, A significa nt increase in LDL cholesterol and a significant decrease in HDL chole sterol were noted during the b.i.d. dosing arm when compared with q. d ay CsA dosing. We conclude that in stable heart transplant patients on ce-a-day CsA dosing results in better GFR and renal plasma flow, a low er nocturnal blood pressure, and an improved lipid profile when compar ed with dosing CsA twice a day.