Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients

INTRODUCTION AND AIM: Calcineurin inhibitor (CNI) dose reduction or late withdrawal may be ineffective for chronic kidney disease (CKD) prevention once it has developed after liver transplantation (LT). We carried out a 2:1 ratio randomized trial to assess whether early withdrawal of CNI followed by initiation of everolimus (Evr) monotherapy in de novo liver transplant would lead to superior renal function compared to a cyclosporine (CsA) based immunosuppression protocol. PATIENTS AND METHODS: All patients were treated with CsA for the first 10 days, then they were randomized to receive Evr in combination with CsA up to day 30, then continued on Evr as monotherapy (Evr Group) or to maintain CsA with/without mycophenolate mofetil in case of CKD (CsA Group). All patients received a basiliximab induction on day 0 and 5 after LT and were tapered off steroids by 5 weeks. Fifty-one consecutive patients were enrolled (Evr n=34; CsA n=17), all of them reached a post-LT follow-up equal or longer than 12 months. All main patient characteristics resulted similar between the two groups in terms of demographics, MELD score and LT indication. RESULTS: There was no statistically significant difference in 1-year patient survival that was 82.4% and 85.3% in CsA and Evr Group respectively. Mean estimated glomerular filtration rate (eGFR), calculated with MDRD formula, was similar in the two groups at randomization, but was significantly better in the Evr Group at 6 months (86.5±36.4 vs. 51.2±13.9 mL/min/1.73m2; p=0.002) and at 12 months (85.6±24.3 vs. 59.8±12 mL/min/1.73m2;p=0.001). At the end of follow-up 9 patients out of 17 (52.9%) in CsA Group and 7 out of 34 (20.6%) in Evr Group experienced a stage ≥3 CKD (eGFR