Reduced Tacrolimus Trough Level Is Reflected by Estimated Glomerular Filtration Rate (eGFR) Changes in Stable Renal Transplantation Recipients: Results of the OPTIMUM Phase 3 Randomized Controlled Study

Abstract

BACKGROUND: Minimizing the tacrolimus dosage in patients with stable allograft function needs further investigation. MATERIAL AND METHODS: We performed an open-label, randomized, controlled study from 2010 to 2016 in 7 tertiary teaching hospitals in Korea and enrolled 345 kidney transplant recipients with a stable graft status. The study group received reduced-dose tacrolimus, 1080-1440 mg/day of enteric-coated mycophenolate sodium (EC-MPS), and corticosteroids. The control group received the standard tacrolimus dosage and 540-720 mg/day of EC-MPS with steroids. The primary endpoint was the mean estimated glomerular filtration rate (eGFR) and change in the eGFR at 12 months after randomization. RESULTS: The mean tacrolimus trough level of the study group was 4.51+/-1.62 ng/mL, which was lower than that of the control group, at 6.75+/-2.82 ng/mL (P<0.001). The primary endpoint was better in the study group in terms of change in eGFR (P<0.001). The month 12 eGFRs were 73.6+/-28.4 and 68.3+/-18.1 mL/min/1.73 m(2) in the study and the control groups, respectively, but the difference did not reach statistical significance (P=0.07). The incidence of adverse events was similar between the study and the control groups. CONCLUSIONS Minimizing tacrolimus to a trough level below 5 ng/mL combined with conventional EC-MPS can be considered in patients with a steady follow-up, as it was associated with small benefits in the changes of the eGFR (Clinicaltrials.gov number: NCT01159080).