The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact...

Authors: Thölking, Gerold Bernhard
Fortmann, Christian
Koch, Raphael
Gerth, Hans Ulrich
Pabst, Dirk
Pavenstädt, Hermann
Kabar, Iyad
Hüsing, Anna Katharina Elisabeth Pia
Wolters, Heiner
Reuter, Stefan Johannes
Suwelack, Barbara
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2014
Date of publication on miami:12.12.2014
Modification date:27.01.2020
Edition statement:[Electronic ed.]
Source:PLoS ONE 9 (2014) 10, 1-8, e111128
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:1932-6203
URN:urn:nbn:de:hbz:6-81319476425
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-81319476425
Other Identifiers:DOI: doi:10.1371/journal.pone.0111128
Digital documents:journal.pone.0111128.pdf

The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies.