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 AND 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 m²), 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 m², experienced a decrease in eGFR in all tacrolimus treatment arms. In patients with lower baseline renal function (eGFR ˂60 mL/min/1.73 m²), 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.

Abdominal Transplant Surgery University Hospitals Leuven Leuven Belgium

Astellas Pharma Europe Ltd Chertsey United Kingdom

Astellas Pharma Medical Affairs Global Northbrook IL USA

BENKAZ Consulting Ltd Cambridge United Kingdom

Department of Abdominal Surgery A 5 Vishnevsky Institute of Surgery Moscow Russian Federation

Department of General Visceral and Transplantation Surgery Hannover Medical School Hannover Germany

Department of General Visceral and Transplantation Surgery Westpfalz Klinikum Hospital Kaiserslautern Germany

Department of General Visceral and Vascular Surgery Jena University Hospital Jena Germany

Department of Nephrology and Organ Transplantation Toulouse University Hospital Toulouse France

Department of Surgery Goethe University Hospital and Clinics Frankfurt Germany

Department of Transplantation and Liver Surgery Clinic Helsinki University Hospital Helsinki Finland

The Transplant Institute Sahlgrenska University Hospital Gothenburg Sweden

Transplant and Hepatobiliary Unit Department of Surgery University of Rome Tor Vergata Rome Italy

Transplantcenter Institute for Clinical and Experimental Medicine Prague Czech Republic

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