Universität zu Köln

Thoelking, Gerold, Filensky, Brigitte, Jehn, Ulrich, Schuette-Nuetgen, Katharina, Koch, Raphael ORCID: 0000-0002-5581-5122, Kurschat, Christine, Pavenstaedt, Hermann, Suwelack, Barbara, Reuter, Stefan and Kuypers, Dirk (2021). Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation. Sci Rep, 11 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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Abstract

Y 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thoelking, Gerold UNSPECIFIED UNSPECIFIED UNSPECIFIED Filensky, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Jehn, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuette-Nuetgen, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Raphael UNSPECIFIED orcid.org/0000-0002-5581-5122 UNSPECIFIED Kurschat, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Pavenstaedt, Hermann UNSPECIFIED UNSPECIFIED UNSPECIFIED Suwelack, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Reuter, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuypers, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-587915
DOI:	10.1038/s41598-021-95201-5
Journal or Publication Title:	Sci Rep
Volume:	11
Number:	1
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TWICE-DAILY TACROLIMUS; EARLY PHASE; OPEN-LABEL; PHARMACOKINETICS; RECIPIENTS; EXPOSURE; FORMULATIONS; ADHERENCE; TRIAL Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58791