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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 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.

Titel: The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation
Verfasser: Thölking, Gerold Bernhard GND
Fortmann, Christian GND
Koch, Raphael
Gerth, Ulrich GND
Pabst, Dirk GND
Pavenstädt, Hermann
Kabar, Iyad GND
Hüsing, Anna Katharina Elisabeth Pia GND
Wolters, Heiner GND
Reuter, Stefan Johannes GND
Suwelack, Barbara
Organisation: FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 23.10.2014
Publikation in MIAMI: 12.12.2014
Datum der letzten Änderung: 27.07.2015
Quelle: PLoS ONE 9 (2014) 10, 1-8, e111128
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-81319476425
DOI: doi:10.1371/journal.pone.0111128
ISSN: 1932-6203