Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation

Abstract Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal fun...

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Autores principales:	Gerold Thölking, Brigitte Filensky, Ulrich Jehn, Katharina Schütte-Nütgen, Raphael Koch, Christine Kurschat, Hermann Pavenstädt, Barbara Suwelack, Stefan Reuter, Dirk Kuypers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63b97591831f44d68328644c0cbbe7db
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spelling	oai:doaj.org-article:63b97591831f44d68328644c0cbbe7db2021-12-02T14:53:43ZIncreased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation10.1038/s41598-021-95201-52045-2322https://doaj.org/article/63b97591831f44d68328644c0cbbe7db2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95201-5https://doaj.org/toc/2045-2322Abstract Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid. Three months after RTx, a Tac concentration to dose ratio (C/D ratio) < 1.0 ng/ml · 1/mL defined fast ER-Tac metabolism and ≥ 1.0 ng/ml · 1/mL slow metabolism. Renal function (estimated glomerular filtration rate, eGFR), first acute rejection (AR), conversion from ER-Tac, graft and patient survival were observed up to 60-months. 610 RTx patients were divided into 192 fast and 418 slow ER-Tac metabolizers. Fast metabolizers showed a decreased eGFR at all time points compared to slow metabolizers. The fast metabolizer group included more patients who were switched from ER-Tac (p < 0.001). First AR occurred more frequently (p = 0.008) in fast metabolizers, while graft and patient survival rates did not differ between groups (p = 0.529 and p = 0.366, respectively). Calculation of the ER-Tac C/D ratio early after RTx may facilitate individualization of immunosuppression and help identify patients at risk for an unfavorable outcome.Gerold ThölkingBrigitte FilenskyUlrich JehnKatharina Schütte-NütgenRaphael KochChristine KurschatHermann PavenstädtBarbara SuwelackStefan ReuterDirk KuypersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gerold Thölking Brigitte Filensky Ulrich Jehn Katharina Schütte-Nütgen Raphael Koch Christine Kurschat Hermann Pavenstädt Barbara Suwelack Stefan Reuter Dirk Kuypers Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
description	Abstract Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid. Three months after RTx, a Tac concentration to dose ratio (C/D ratio) < 1.0 ng/ml · 1/mL defined fast ER-Tac metabolism and ≥ 1.0 ng/ml · 1/mL slow metabolism. Renal function (estimated glomerular filtration rate, eGFR), first acute rejection (AR), conversion from ER-Tac, graft and patient survival were observed up to 60-months. 610 RTx patients were divided into 192 fast and 418 slow ER-Tac metabolizers. Fast metabolizers showed a decreased eGFR at all time points compared to slow metabolizers. The fast metabolizer group included more patients who were switched from ER-Tac (p < 0.001). First AR occurred more frequently (p = 0.008) in fast metabolizers, while graft and patient survival rates did not differ between groups (p = 0.529 and p = 0.366, respectively). Calculation of the ER-Tac C/D ratio early after RTx may facilitate individualization of immunosuppression and help identify patients at risk for an unfavorable outcome.
format	article
author	Gerold Thölking Brigitte Filensky Ulrich Jehn Katharina Schütte-Nütgen Raphael Koch Christine Kurschat Hermann Pavenstädt Barbara Suwelack Stefan Reuter Dirk Kuypers
author_facet	Gerold Thölking Brigitte Filensky Ulrich Jehn Katharina Schütte-Nütgen Raphael Koch Christine Kurschat Hermann Pavenstädt Barbara Suwelack Stefan Reuter Dirk Kuypers
author_sort	Gerold Thölking
title	Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
title_short	Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
title_full	Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
title_fullStr	Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
title_full_unstemmed	Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
title_sort	increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/63b97591831f44d68328644c0cbbe7db
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Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation

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