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

Abstract

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. 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 C2 values were 725, 400 and 306 ng/ml; for all cohorts, sirolimus C0 = 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. 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. 80% reduction in de novo CsA exposure with antibody induction improved renal function at 4 years compared with 50 or 66% reductions.