The Effect of Donor Age and Recipient Characteristics on Renal Outcomes in Patients Receiving Prolonged-Release Tacrolimus After Liver Transplantation: Post-Hoc Analyses of the DIAMOND Study.

Background: The DIAMOND study of de novo liver transplant patients showed that prolonged-release tacrolimus exposure in the acute post-transplant period maintained renal function over 24 weeks of treatment. To assess these findings further, we performed a post-hoc analysis in patients according to baseline kidney function, Model for End-stage Liver Disease [MELD] scores, and donor age. Material/Methods: Patients received prolonged-release tacrolimus (initial-dose, Arm 1: 0.2 mg/kg/day, Arm 2: 0.15-0.175 mg/kg/day, Arm 3: 0.2 mg/kg/day delayed until Day 5), mycophenolate mofetil and 1 steroid bolus. Arms 2 and 3 also received basiliximab. The recommended tacrolimus target trough levels to Day 42 post-transplantation were 5-15 ng/mL in all arms. In this post-hoc analysis, change in renal outcome, based on estimated glomerular filtration rate (eGFR), Modified Diet in Renal Disease-4 (MDRD4), values from baseline to Week 24 post-transplantation, were assessed according to baseline patient factors: eGFR (>= 60 and <60 mL/min/1.73 m(2)), MELD score (<25 and >= 25) and donor age (<50 and >= 50 years). Results: Baseline characteristics were comparable (Arms 1-3: n=283, n=287, n=274, respectively). Patients with baseline renal function, eGFR >= 60 mL/min/1.73 m(2), experienced a decrease in eGFR in all tacrolimus treatment arms. In patients with lower baseline renal function (eGFR <60 mL/min/1.73 m(2)), an advantage for renal function was observed with both the early lower-dose and delayed higher-dose tacrolimus regimens compared with the early introduction of higher-dose tacrolimus. At Week 24, renal function was higher in the early-lower tacrolimus arm with older donors, and the delayed higher-dose tacrolimus arm with younger donors, both compared with early higher-dose tacrolimus. Conclusions: Pre-transplantation factors, such as renal function and donor age, could guide the choice of prolonged-release tacrolimus regimen following liver transplantation.