TY  - JOUR
AB  - BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate – defined as the blood concentration normalized by its daily dose (the C/D ratio) – is associated with post-LTx renal impairment. MATERIAL AND METHODS: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone. Six months after LTx, 115 patients were categorized into 1 of 2 groups based on their Tac C/D ratio (<1.09 or ≥1.09): fast (n=58) or slow (n=57) metabolizers. The renal function was determined 36 months after LTx using the estimated glomerular filtration rate (eGFR) as described by Cockcroft and Gault. RESULTS: At the time of LTx there was no statistically significant difference between the eGFR of fast and slow metabolizers. Six months (P=0.016), 12 months (P=0.001), and 36 months (P=0.018) after LTx, fast Tac metabolizers had significantly more impaired renal function than slow metabolizers. Because of a presumption of CNI nephrotoxicity, 32.8% of fast metabolizers and 14.0% of slow metabolizers were switched from Tac to other immunosuppressants (P=0.027). CONCLUSIONS: In this study, the Tac metabolism rate appears to influence renal function after LTx, suggesting that a C/D ratio of <1.09 is associated with increased CNI nephrotoxicity in LTx recipients.
AU  - Thölking, Gerold Bernhard
AU  - Siats, Lea
AU  - Siats, Lea Marieke
AU  - Fortmann, Christian
AU  - Fortmann, Christian Patrick
AU  - Koch, Raphael
AU  - Hüsing, Anna Katharina Elisabeth Pia
AU  - Cicinnati, Vito R.
AU  - Gerth, Hans Ulrich
AU  - Gerth, Hans Ulrich Volker
AU  - Gerth, Hans U.
AU  - Wolters, Heiner
AU  - Wolters, Heiner Huber
AU  - Anthoni, Christoph
AU  - Pavenstädt, Hermann-Joseph
AU  - Suwelack, Barbara
AU  - Schmidt, Hartmut
AU  - Kabar, Iyad
DA  - 2016-03-22
DO  - 10.12659/AOT.895898
KW  - Calcineurin
KW  - Liver Transplantation
KW  - Metabolism
KW  - renal insufficiency
KW  - Tacrolimus
LA  - eng
N1  - Annals of Transplantation 21 (2016), 167-179
N1  - Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2016-03-22
SN  - 2329-0358
TI  - Tacrolimus concentration/dose ratio influences renal functions after liver transplantation
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-65289635569
Y2  - 2024-11-21T16:19:06
ER  -