Gerold Thölking1, Lea Siats1, Christian Fortmann1, Raphael Koch2, Anna Hüsing3, Vito R Cicinnati3, Hans Ulrich Gerth4, Heiner H Wolters5, Christoph Anthoni5, Hermann Pavenstädt4, Barbara Suwelack4, Hartmut H Schmidt3, Iyad Kabar3. 1. Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital Münster, Münster, Germany. 2. Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany. 3. Department of Transplant Medicine, University Hospital of Münster, Münster, Germany. 4. Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany. 5. Department of General Surgery, University Hospital of Münster, Münster, Germany.
Abstract
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.
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-LTxrenal 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.
Authors: Gerold Thölking; Katharina Schuette-Nuetgen; Thomas Vogl; Ulrich Dobrindt; Barbara C Kahl; Marcus Brand; Hermann Pavenstädt; Barbara Suwelack; Raphael Koch; Stefan Reuter Journal: PLoS One Date: 2017-11-16 Impact factor: 3.240
Authors: Benas Prusinskas; Sinja Ohlsson; Simone Kathemann; Denisa Pilic; Kristina Kampmann; Rainer Büscher; Andreas Paul; Lars Pape; Peter F Hoyer; Elke Lainka Journal: Front Pediatr Date: 2021-06-02 Impact factor: 3.418
Authors: Gerold Thölking; Katharina Schütte-Nütgen; Julia Schmitz; Alexandros Rovas; Maximilian Dahmen; Joachim Bautz; Ulrich Jehn; Hermann Pavenstädt; Barbara Heitplatz; Veerle Van Marck; Barbara Suwelack; Stefan Reuter Journal: J Clin Med Date: 2019-10-02 Impact factor: 4.241
Authors: Gerold Thölking; Nils Hendrik Gillhaus; Katharina Schütte-Nütgen; Hermann Pavenstädt; Raphael Koch; Barbara Suwelack; Stefan Reuter Journal: J Clin Med Date: 2020-01-23 Impact factor: 4.241