Early Conversion to Everolimus in Renal Transplant Recipients

Abstract

Background: Despite being an effective immunosuppressive agent, the calcineurin inhibitors (ciclosporin and tacrolimus) are associated with nephrotoxicity, chronic allograft nephropathy and long term graft loss. The authors proposed that the early replacement of calcineurin inhibitors with everolimus (a mammalian-target-of-rapamycin inhibitor) may be an effective strategy of immunosuppression following renal transplantation, and may improve renal function without compromising efficacy. We present our experience of early conversion to everolimus after 6 months of renal transplantation. Material and methods: Patients who underwent renal transplantation from 2009 to 2011 were enrolled in the study. In is prospective open label study. Patients received triple maintenance immunosuppression; prenisolone 20mg/day, tacrolimus 0.1mg/kg/day, Mycophenolate mofitil 2.0g/day. Basiliximab induction (20 mg, intravenously, on day 0 and on day 4) was given to patients with spousal donors. After 6 months of renal transplantation tacrolimus was replaced by everolimus. (trough concentrations of 6-10 ng/mL] Results: Totally 33 renal transplant recipients were converted to everolimus during this period. Female to male ratio was 1: 5.6. The mean age was 35.8 years. In 3 patients (9.09%), tacrolimus was changed to everolimus at 3 months due to tacrolimus toxicity, another 3 patients (9.09%), mycophenolate mofitil was convered to everolimus due to drug induces bone marrow depression and in 27 patients (81.81%) everolimus was started after 6 months of renal transplantation as a protocol. Ten patients (30.3%) received basileximab, nine (27.27%) were spousal transplantation and one (3.03%) was deseased donor transplantation. Kidney donor was mother in 10 patients (30.3%), father in 3 (9.09%), brother in 5(15.15%) and sister in 4 patients (12.12%). Mean serum creatinine before start of everlimus was 1.34mg/Dl, and GFR was 54ml/min. At 6 months and 1 year follow-up, patient and graft survivals were 100%. None of the 33 patients suffered rejection. Mean serum creatinine and GFR at 6 months and 1 year were 1. 26 mg/dl, 59 ml/min and 1.21mg/dl, 61/min respectively. Mean 24 hours urinary proteiuria before conversion to everolimus, at 6 months and at 1 year after conversion to everlimus were 342 mg, 397mg and 413 mg. Five patients (15.15%) suffered CMV infection after convertion to everolimus and one (3.03%) patient suffered B K Virus nephropathy. Eighteen patients (54.54%) developed hyperlipidemia after conversion to everolimus. Conclusion: Early elimination of calcineurin inhibitor by use of everolimus-based immunosuppression improved renal function at 12 months while maintaining efficacy and safety, indicating that this strategy may facilitate improved long-term outcomes in selected patients.