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.

Trunecka, P., Klempnauer, J., Bechstein, W.o., Pirenne, J., Bennet, W., Zhao, A., et al. (2019). 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. ANNALS OF TRANSPLANTATION, 24, 319-327 [10.12659/AOT.913103].

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

Brown M.;Tisone G.
2019

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/18
English
Glomerular Filtration Rate; Immunosuppressive Agents; Liver Transplantation; Tacrolimus; Adult; Age Factors; Aged; Delayed-Action Preparations; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Tissue Donors; Transplant Recipients
Trunecka, P., Klempnauer, J., Bechstein, W.o., Pirenne, J., Bennet, W., Zhao, A., et al. (2019). 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. ANNALS OF TRANSPLANTATION, 24, 319-327 [10.12659/AOT.913103].
Trunecka, P; Klempnauer, J; Bechstein, Wo; Pirenne, J; Bennet, W; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Monch, C; Brown, M; Undre, N; Kazeem, G; Tisone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/241530
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