Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation
Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal func...
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doaj-4df703fdc97d4d14babe9e739ab050e82020-11-25T01:27:08ZengMDPI AGJournal of Clinical Medicine2077-03832019-04-018558710.3390/jcm8050587jcm8050587Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio CalculationKatharina Schütte-Nütgen0Gerold Thölking1Julia Steinke2Hermann Pavenstädt3René Schmidt4Barbara Suwelack5Stefan Reuter6Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyDepartment of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyDepartment of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyDepartment of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyInstitute of Biostatistics and Clinical Research, University Hospital of Münster, 48149 Münster, GermanyDepartment of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyDepartment of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, GermanyTacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal function after RTx. Therefore, we hypothesize that the Tac metabolism rate impacts patient and graft survival after RTx. We analyzed all patients who received a RTx between January 2007 and December 2012 and were initially treated with an immunosuppressive regimen containing Tac (Prograf<sup>®</sup>), mycophenolate mofetil, prednisolone and induction therapy. Patients with a Tac C/D ratio <1.05 ng/mL × 1/mg at three months after RTx were characterized as fast metabolizers and those with a C/D ratio ≥1.05 ng/mL × 1/mg as slow metabolizers. Five-year patient and overall graft survival were noticeably reduced in fast metabolizers. Further, fast metabolizers showed a faster decline of eGFR (estimated glomerular filtration rate) within five years after RTx and a higher rejection rate compared to slow metabolizers. Calculation of the Tac C/D ratio three months after RTx may assist physicians in their daily clinical routine to identify Tac-treated patients at risk for the development of inferior graft function, acute rejections, or even higher mortality.https://www.mdpi.com/2077-0383/8/5/587kidney transplantationtacrolimusC/D-ratiopharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katharina Schütte-Nütgen Gerold Thölking Julia Steinke Hermann Pavenstädt René Schmidt Barbara Suwelack Stefan Reuter |
spellingShingle |
Katharina Schütte-Nütgen Gerold Thölking Julia Steinke Hermann Pavenstädt René Schmidt Barbara Suwelack Stefan Reuter Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation Journal of Clinical Medicine kidney transplantation tacrolimus C/D-ratio pharmacokinetics |
author_facet |
Katharina Schütte-Nütgen Gerold Thölking Julia Steinke Hermann Pavenstädt René Schmidt Barbara Suwelack Stefan Reuter |
author_sort |
Katharina Schütte-Nütgen |
title |
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation |
title_short |
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation |
title_full |
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation |
title_fullStr |
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation |
title_full_unstemmed |
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation |
title_sort |
fast tac metabolizers at risk—it is time for a c/d ratio calculation |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-04-01 |
description |
Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal function after RTx. Therefore, we hypothesize that the Tac metabolism rate impacts patient and graft survival after RTx. We analyzed all patients who received a RTx between January 2007 and December 2012 and were initially treated with an immunosuppressive regimen containing Tac (Prograf<sup>®</sup>), mycophenolate mofetil, prednisolone and induction therapy. Patients with a Tac C/D ratio <1.05 ng/mL × 1/mg at three months after RTx were characterized as fast metabolizers and those with a C/D ratio ≥1.05 ng/mL × 1/mg as slow metabolizers. Five-year patient and overall graft survival were noticeably reduced in fast metabolizers. Further, fast metabolizers showed a faster decline of eGFR (estimated glomerular filtration rate) within five years after RTx and a higher rejection rate compared to slow metabolizers. Calculation of the Tac C/D ratio three months after RTx may assist physicians in their daily clinical routine to identify Tac-treated patients at risk for the development of inferior graft function, acute rejections, or even higher mortality. |
topic |
kidney transplantation tacrolimus C/D-ratio pharmacokinetics |
url |
https://www.mdpi.com/2077-0383/8/5/587 |
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