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...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4207775?pdf=render |
id |
doaj-7722cc0a139d4a60b08dee950eac6162 |
---|---|
record_format |
Article |
spelling |
doaj-7722cc0a139d4a60b08dee950eac61622020-11-25T02:47:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11112810.1371/journal.pone.0111128The tacrolimus metabolism rate influences renal function after kidney transplantation.Gerold ThölkingChristian FortmannRaphael KochHans Ulrich GerthDirk PabstHermann PavenstädtIyad KabarAnna HüsingHeiner WoltersStefan ReuterBarbara SuwelackThe 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.http://europepmc.org/articles/PMC4207775?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gerold Thölking Christian Fortmann Raphael Koch Hans Ulrich Gerth Dirk Pabst Hermann Pavenstädt Iyad Kabar Anna Hüsing Heiner Wolters Stefan Reuter Barbara Suwelack |
spellingShingle |
Gerold Thölking Christian Fortmann Raphael Koch Hans Ulrich Gerth Dirk Pabst Hermann Pavenstädt Iyad Kabar Anna Hüsing Heiner Wolters Stefan Reuter Barbara Suwelack The tacrolimus metabolism rate influences renal function after kidney transplantation. PLoS ONE |
author_facet |
Gerold Thölking Christian Fortmann Raphael Koch Hans Ulrich Gerth Dirk Pabst Hermann Pavenstädt Iyad Kabar Anna Hüsing Heiner Wolters Stefan Reuter Barbara Suwelack |
author_sort |
Gerold Thölking |
title |
The tacrolimus metabolism rate influences renal function after kidney transplantation. |
title_short |
The tacrolimus metabolism rate influences renal function after kidney transplantation. |
title_full |
The tacrolimus metabolism rate influences renal function after kidney transplantation. |
title_fullStr |
The tacrolimus metabolism rate influences renal function after kidney transplantation. |
title_full_unstemmed |
The tacrolimus metabolism rate influences renal function after kidney transplantation. |
title_sort |
tacrolimus metabolism rate influences renal function after kidney transplantation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4207775?pdf=render |
work_keys_str_mv |
AT geroldtholking thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT christianfortmann thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT raphaelkoch thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT hansulrichgerth thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT dirkpabst thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT hermannpavenstadt thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT iyadkabar thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT annahusing thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT heinerwolters thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT stefanreuter thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT barbarasuwelack thetacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT geroldtholking tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT christianfortmann tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT raphaelkoch tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT hansulrichgerth tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT dirkpabst tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT hermannpavenstadt tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT iyadkabar tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT annahusing tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT heinerwolters tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT stefanreuter tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation AT barbarasuwelack tacrolimusmetabolismrateinfluencesrenalfunctionafterkidneytransplantation |
_version_ |
1724754053880086528 |