Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.

Introduction. This study evaluated whether cyclosporine (CsA) could be elim inated from a sirolimus (Rapamune, rapamycin, SRL)-CsA-steroid (ST) regimen at 3 months. Methods. This was an open-label study conducted in Europe, Australia, and C anada. Upon enrollment, 525 primary (90%) or secondary (10%) renal allograf t recipients with cadaveric (89%) or living (11%) donors received 2 mg of s irolimus (troughs >5 ng/ml), CsA, and steroids. At 3 months 2 weeks, eligib le patients were randomized (1:1) to remain on SRL-CsA-ST or to have CsA wi thdrawn and therapy continued with SRL (troughs 20-30 ng/ml)-ST. Results. At 12 months, overall graft and patient survival were 89.1% and 94 .9%, respectively. In the 430 (82%) randomized patients, there was no diffe rence in graft survival (95.8% vs. 97.2%, SRL-CsA-ST vs. SRL-ST) or patient survival (97.2% vs. 98.1%, respectively). The incidence of biopsy-confirme d primary acute rejection was 13.1% during the prerandomization period. Aft er randomization, the acute rejection rates were 4.2% and 9.8% for SRL-CsA- ST and SRL-ST, respectively (P=0.035). Renal function (calculated glomerula r filtration rate, 57 vs. 63 ml/min, P <0.001) and blood pressure significa ntly improved when CsA was withdrawn. Hypertension, CsA nephrotoxicity, hyp eruricemia, and Herpes zoster occurred statistically more frequently in pat ients remaining on CsA, whereas thrombocytopenia, abnormal liver function t ests, and hypokalemia. were reported more often for SRL-ST therapy. Conclusion. Sirolimus, CsA, and steroids for 3 months posttransplant, follo wed by elimination of CsA, is a safe and effective alternative to continuou s therapy with sirolimus, CsA, and steroids that can result in better renal function and lower blood pressure.