EFFECTS OF ISRADIPINE ON RENAL-FUNCTION IN CYCLOSPORINE-TREATED RENAL TRANSPLANTED PATIENTS

The renal effects of the calcium-channel antagonist isradipine were evaluated in cyclosporin A (CsA)-treated renal allografted patients more than 5 months after transplantation. Twelve patients with stable renal function were given placebo for 2 weeks and then isradipine 1.25 mg x 2 for 1 week and 2.5 mg x 2 for the next 3 weeks in an open trial. The CsA dose was unchanged during the study. Isradipine did not interfere with the pharmacokinetics of CsA as both whole blood trough and peak levels were unchanged. Isradipine reduced mean arterial blood pressure (MAP) from 117.0 +/- 1.8 to 106.3 +/- 1.9 mmHg (P < 0.01). The renal effects were studied during water diuresis 1-3 h after drug intake. Para-aminohippurate clearance (C(PAH)) increased from 256.4 +/- 21.5 to 291.5 +/- 26.3 ml/min (P < 0.05), renal vascular resistance was reduced by 21.5% (P < 0.01) and inulin clearance (C(In)) was unchanged. Fractional proximal reabsorption, calculated from lithium clearance (C(Li)), was reduced by 11.9% (P < 0.01) by isradipine. Isradipine also reduced proximal reabsorption of sodium (APR(Na)) and increased distal sodium delivery (DD(Na)). Distal sodium reabsorption (ADR(Na)) and free-water clearance (C(H2O)) were significantly increased. Urinary excretion of enzymes and proteins was unchanged by isradipine.