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World J Transplant. Feb 24, 2017; 7(1): 26-33
Published online Feb 24, 2017. doi: 10.5500/wjt.v7.i1.26
Influence of tacrolimus metabolism rate on renal function after solid organ transplantation
Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter
Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany
Author contributions: Thölking G wrote the paper, analyzed the data and designed the study; Gerth HU collected the data and wrote the paper; Schuette-Nuetgen K collected the data and wrote the paper; Reuter S designed the study and wrote the paper.
Conflict-of-interest statement: Gerold Thölking, Hans Ulrich Gerth and Katharina Schuette-Nuetgen declare no conflict of interests for this article; Stefan Reuter declares that he has received travel support from Astellas and lecture fees from Chiesi.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gerold Thölking, MD, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster, Germany. gerold.thoelking@ukmuenster.de
Telephone: +49-251-8348001 Fax: +49-251-8346979
Received: October 5, 2016
Peer-review started: October 7, 2016
First decision: November 11, 2016
Revised: November 22, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: February 24, 2017
Processing time: 139 Days and 12.3 Hours
Abstract

The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury. Unfortunately, TAC pharmacokinetic is determined by a whole bunch of parameters. However, for daily clinical routine a simple application strategy is needed. To address this problem, we and others have evaluated a simple calculation method in which the TAC blood trough concentration (C) is divided by the daily dose (D). Fast TAC metabolism (C/D ratio < 1.05) was identified as a potential risk factor for an inferior kidney function after transplantation. In this regard, we recently showed a strong association between fast TAC metabolism and CNI nephrotoxicity as well as BKV infection. Therefore, the TAC C/D ratio may assist transplant clinicians in a simple way to individualize the immunosuppressive regimen.

Keywords: Tacrolimus; Liver; Metabolism; Transplantation; Kidney

Core tip: The calcineurin inhibitor tacrolimus (TAC) is the mainstay of the immunosuppressive regimen after solid organ transplantation. Nevertheless, TAC can cause nephrotoxicity even at low blood trough levels. Thus, other factors than the TAC trough level might be responsible for kidney injury. Recently published studies showed a strong association between fast TAC metabolism and nephrotoxicity as well as BK virus infection. The TAC metabolism rate defined as the TAC concentration/dose ratio is a cost neutral tool to identify patients at risk for TAC-associated decline in renal function after transplantation.