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 nep hrotoxicity and hypertension that may be hemodynamically mediated. Thi s study was undertaken to see if the calcium channel blocker, isradipi ne, could improve renal hemodynamics by decreasing renal vascular resi stance 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 pr essure, creatinine clearance, cyclosporine trough levels, and renal pl asma 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 significa ntly (p < 0.001) from baseline to 8 weeks with isradipine. Sbp decreas ed from 166 +/- 18 to 142 +/- 14 mmHg and Dbp decreased from 97 +/- 8 to 82 +/- 10 mmHg (mean +/- 1 SD). Renal vascular resistance, calculat ed from mean arterial pressure and renal blood flow, decreased signifi cantly (p < 0.002) from 0.57 +/- 0.21 to 0.41 +/- 0.12 mmHg/ml/min (me an +/- 1 SD). Isradipine appeared to have no significant effect on cyc losporine trough levels, creatinine clearance, or renal plasma flow. T his study shows a role for isradipine use in renal transplant recipien ts on cyclosporine. Renal vasoconstriction caused by cyclosporine may be partially prevented with isradipine therapy. Furthermore, isradipin e is effective in the treatment of hypertension in renal transplant re cipients without affecting cyclosporine levels.