Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression

Background. Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown. Methods. This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) Plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (I g twice daily). Steroid administration was identical for all groups. Results. A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57 +/- 12, 65.2 +/- 20, 73.5 +/- 27 ml/min,P=0.044), the Jelliffe-2 (51.5 +/- 16,56 +/- 19,59.4 +/- 19ml/min/1.73 m(2), P=0.041) and the Modification of Diet in Renal Disease equations (53 +/- 17, 58.5 +/- 20, 61.6 +/- 1-22 ml/min/1.73 m(2), P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytornegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008). Conclusions. Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.