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.

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 m² 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).