Conversion from Tacrolimus (TAC) to Sirolimus (SRL)-Based Immunosuppressive Regimen in Kidney Transplant Recipients: 2 Years Results

Abstract

Introduction: This multicenter prospective study evaluated renal function of kidney transplant (KT) recipients randomized after the transplant surgery to undergo planned conversion from TAC to SRL-based immunosuppressive regimen 3 months after transplantation. Methods: Low risk recipients of first KT receiving TAC, mycophenolate sodium (MPS) and prednisone (PRED) showing good renal function, no proteinuria and no previous severe acute rejection at 3 months were converted from TAC to SRL in a randomized fashion. Results: Of 320 RKT enrolled in this study, 299 (93%) were randomized to be converted to SRL (n= 148) or to stay on TAC (n= 151). The mean age of this population was 45±13 years; 57 % caucasian ethnicity, 69 % male sex and 50% RKT from deceased donor. During the first 3 months 10 (3%) patients discontinued the study. Of 289 patients reaching month 3, 79 (27%) did not meet criteria for intervention, 100 were converted to SRL and 110 were maintained on TAC. No differences were observed in mean cGFR at 3 months (60±20 and 64±24, p= 0.069 ml/min) and 24 months (67±25 vs. 72±24 ml/ min, p= 0.278) in SRL and TAC, respectively. The incidence of biopsy proven acute rejection (BCAR) was comparable at 3 months (19.6% vs. 20.0 %), but higher in patients on SRL (10% vs. 2%, p= 0.110) between 3 and 24 months. At 3 months, TAC mean trough level was 8.6±5.3 ng/mL, MPS dose 1349±224 mg/day and PRED dose 9.0±6.0 mg/day. At month 24, mean SRL trough concentration was 8.0±3.0 ng/mL and mean MPS dose was 1292 ± 253 mg/day for patients receiving SRL while mean TAC trough concetnration was 6.0±3.5 ng/mL and mean MPS dose was 1306±256 mg/day for patients maintained on TAC. There were no differences in the incidence of treatment discontinuation (13 % vs. 15 %), graft loss (1% vs. 3%) or death (2 % vs. 4%), respectively. Conclusions: This final analysis indicates that 73% of KTR reaching 3 months fulfilled the criteria to undergo conversion from TAC to SRL. Conversion was associated with increased risk of acute rejection, comparable tolerability but no difference in cGFR at 24 months compared to patients maintained on TAC.