Addition of induction therapy offsets the hazard of marked calcineurin minimization among renal transplant recipients treated with sirolimus

作者：Kahan B D^*; Benavides C; Schoenberg L; Podbielski J; Green C

来源：Clinical Nephrology, 2010, 73(5): 344-353.

• sirolimus
• calcineurin minimization

Aims: We sought to examine the improvement in renal function with preserved immunosuppression consequent to reducing de novo cyclosporine (CsA) doses combined with sirolimus and induction antibody treatment. Materials and methods: 408 renal recipients treated de novo with CsA-sirolimus included 91 patients who received high (> 5); 125, medium (2.5 - 5.0); or 192, low CsA doses (< 2.5 mg/kg/day) together with induction antibody among 5, 48 and 68% of subjects, respectively. At 2 years we excluded 21 (23), 30 (24) and 49 (25%) subjects who experienced the composite end-point, yielding 70 (71), 95 (76) and 143 (74%) cases, whose mean de novo CsA C(2) values were 725, 400 and 306 ng/ml; for all cohorts, sirolimus C(0) = 10 - 15 de novo and 8 - 12 ng/ml during maintenance treatment. The primary end-point-mean 4-year GFR by aMDRD - ascribed "0" to patients who experienced death or graft loss after 2 years. Results: Although low-dose subjects were older (p = 0.008) and heavier (p < 0.001) with grafts exposed to longer cold ischemia times (p < 0.001), they displayed greater GFR: 64.8 versus 48.4 among the high and 54.1 ml/min/1.73 m(2) in the medium dose arms (p = 0.002). Polychotomous logistic regression revealed significant GFR predictors to be CsA dose (p = 0.015) and younger donor age (p < 0.001). Between 2 and 4 years, the incidences of the composite end-point were 17, 14 and 16%; including 13, 10 and 11% rejections. Conclusion: 80% reduction in de novo CsA exposure with antibody induction improved renal function at 4 years compared with 50 or 66% reductions.

• 出版日期2010-5