Conversion from Tacrolimus (TAC) to Sirolimus (SRL)-Based Immunosuppressive Regimen in Kidney Transplant Recipients: 1 Year Results

Abstract

This multicenter prospective study evaluates renal function (RF) of kidney transplant recipients (KTR) who underwent planned conversion from TAC to SRL-based regimen 3 months (m) after transplantation (tx) Methods: Low risk KTR receiving TAC, mycophenolate sodium (MPS) and prednisone showing good RF, no proteinuria and no previous severe acute rejection (AR) at 3 m were randomized after the tx to be converted to SRL. The primary outcome is calculated glomerular filtration rate (cGFR) at 24 months using intention-to-treat analysis. Results: Of 296 KTR enrolled in this study and reaching 12m, 277 were randomized to be converted to SRL (n=136) or to stay on TAC (n=141). The mean age was 45.0 years; 55.4% caucasian and 70.9% male. During the first 3 months 14 (5%) patients discontinued the study. Of 263 patients reaching 3m, 58 (22%) did not meet criteria for intervention, 110 were converted to SRL and 95 were maintained on TAC. At 3 m, TAC mean trough level was 7.1 ng/mL, mean MPS dose was 1349.3±244.4 mg/day and mean prednisone dose 8.0±4.9 mg/day. No differences were observed in mean cGFR at 3 months (64.4±19.8 and 66.2±19.5 ml/min) and 12 m (74.8±25.7 vs. 70.2±19.1 ml/min), respectively. The incidence of biopsy proven AR was comparable at 3 m (15% vs. 17%), but higher in patients on SRL (5.2% vs. 1.8%) between 3 and 12 m. At 12m, KTR on SRL showed mean trough level of 8.5±3.1 ng/mL and mean MPS dose of 1316.8±234.8 mg/day while KTR on TAC showed mean trough level of 5.8±2.7ng/mL and mean MPS dose of 1365.2 ± 213.3 mg/day. There were no differences in the incidence of treatment discontinuation (7.4% vs. 5.4%), graft loss (1.1% vs. 0.9%) or death (0.9% vs. 1.8%), respectively. Conclusions: This preliminary analysis indicates that 78% of KTR reaching 3 m had criteria to convert from TAC to SRL. Conversion was associated with increased risk of AR, comparable tolerability but no difference in cGFR at 12 m compared to KTR maintained on TAC.