The tacrolimus metabolism rate influences renal function after kidney transplantation

Gerold Thölking, Christian Fortmann, Raphael Koch, Hans Ulrich Gerth, Dirk Pabst, Hermann Pavenstädt, Iyad Kabar, Anna Hüsing, Heiner Wolters, Stefan Reuter, Barbara Suwelack

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere111128
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 23 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Thölking, G., Fortmann, C., Koch, R., Gerth, H. U., Pabst, D., Pavenstädt, H., Kabar, I., Hüsing, A., Wolters, H., Reuter, S., & Suwelack, B. (2014). The tacrolimus metabolism rate influences renal function after kidney transplantation. PloS one, 9(10), [e111128]. https://doi.org/10.1371/journal.pone.0111128