Effects of isradipine on renal hemodynamics in renal transplant patients treated with cyclosporine.

Cyclosporine A is the mainstay of modern immunosuppressant therapy in human organ transplants. However, its use has been associated with nephrotoxicity and hypertension that may be hemodynamically mediated. This study was undertaken to see if the calcium channel blocker, isradipine, could improve renal hemodynamics by decreasing renal vascular resistance and to determine its effects on cyclosporine pharmacokinetics. Eighteen hypertensive renal transplant recipients (3 to 60 months post transplant) were enrolled. Antihypertensive medications were stopped. Patients were placed on isradipine and followed for 8 weeks. Blood pressure, creatinine clearance, cyclosporine trough levels, and renal plasma flow using p-aminohippurate clearance, were measured pre- and at 8 weeks of therapy. Only one patient did not complete renal plasma flow measurement. Systolic and diastolic blood pressures dropped significantly (p < 0.001) from baseline to 8 weeks with isradipine. Sbp decreased from 166 +/- 18 to 142 +/- 14 mmHg and Dbp decreased from 97 +/- 8 to 82 +/- 10 mmHg (mean +/- 1 SD). Renal vascular resistance, calculated from mean arterial pressure and renal blood flow, decreased significantly (p < 0.002) from 0.57 +/- 0.21 to 0.41 +/- 0.12 mmHg/ml/min (mean +/- 1 SD). Isradipine appeared to have no significant effect on cyclosporine trough levels, creatinine clearance, or renal plasma flow. This study shows a role for isradipine use in renal transplant recipients on cyclosporine. Renal vasoconstriction caused by cyclosporine may be partially prevented with isradipine therapy. Furthermore, isradipine is effective in the treatment of hypertension in renal transplant recipients without affecting cyclosporine levels.