The effect of donor age and recipient characteristics on renal outcomes in patients receiving prolongedrelease 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 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.

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Author:Pavel Trunečka, Jürgen KlempnauerGND, Wolf Otto BechsteinORCiDGND, Jacques Pirenne, William Bennet, Alexey Zhao, Helena Isoniemi, Lionel Rostaing, Utz Settmacher, Christian MönchGND, Malcolm Brown, Nasrullah Undre, Gbenga Kazeem, Giuseppe Tisone
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Parent Title (English):Annals of transplantation
Publisher:Polish Transplantation Society with the co-operation of the Czech Transplantation Society and the Hungarian Transplantation Society
Place of publication:Warsaw
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/06/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:DIAMOND study group
Release Date:2020/01/20
Tag:Glomerular Filtration Rate; Immunosuppressive Agents; Liver Transplantation; Tacrolimus
Page Number:9
First Page:319
Last Page:327
This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0