Cargando…
Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial
BACKGROUND: Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level o...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535983/ https://www.ncbi.nlm.nih.gov/pubmed/26270340 http://dx.doi.org/10.1371/journal.pone.0135674 |
_version_ | 1782385682930466816 |
---|---|
author | Plischke, Max Riegersperger, Markus Dunkler, Daniela Heinze, Georg Kikić, Željko Winkelmayer, Wolfgang C. Sunder-Plassmann, Gere |
author_facet | Plischke, Max Riegersperger, Markus Dunkler, Daniela Heinze, Georg Kikić, Željko Winkelmayer, Wolfgang C. Sunder-Plassmann, Gere |
author_sort | Plischke, Max |
collection | PubMed |
description | BACKGROUND: Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level of GFR and offer increased statistical power. METHODS: Secondary analysis of a randomized controlled trial of CSA treated kidney transplant recipients with stable graft function assigned to receive 0.1 mg/kg/day TAC (target 5–8 ng/ml) or to continue CSA based immunosuppression (target 70–150 ng/ml) at a 2:1 ratio. Renal graft function was estimated via the MDRD (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) formulas. RESULTS: Forty-five patients continued CSA and 96 patients were converted to TAC with a median follow up of 24 months. Baseline demographics (except for recipient age) including native kidney disease, transplant characteristics, kidney graft function, medication use and comorbid conditions did not differ between groups. In respect to long-term renal graft function, linear mixed models showed significantly improved eGFR trajectories (eGFR(MDRD): p<0.001, eGFR(CKD-EPI): p<0.001) in the TAC versus CSA group over 24 months of follow up. Estimated eGFR(CKD-EPI) group differences between TAC and CSA were −3.49 (p = 0.019) at 3 months, −5.50 (p<0.001) at 12 months, and −4.48 ml/min/1.73m(2) (p = 0.003) at 24 months of follow up. Baseline eGFR was a significant predictor of eGFR trajectories (eGFR(MDRD): p<0.001, eGFR(CKD-EPI): p<0.001). Significant effects for randomization group were evident despite short-term trough levels in the supratherapeutic range (27% (n = 26) of TAC patients at week one). Median TAC trough levels were within target range at week 4 after conversion. CONCLUSION: Conversion of CSA treated kidney transplant recipients with stable graft function to TAC (target 5–8 ng/ml) showed significantly improved long-term eGFR trajectories when compared to CSA maintenance (target 70–150 ng/ml). TRIAL REGISTRATION: ClinicalTrials.gov NCT00182559 EudraCT identifier: 2004-004209-98 |
format | Online Article Text |
id | pubmed-4535983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45359832015-08-20 Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial Plischke, Max Riegersperger, Markus Dunkler, Daniela Heinze, Georg Kikić, Željko Winkelmayer, Wolfgang C. Sunder-Plassmann, Gere PLoS One Research Article BACKGROUND: Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level of GFR and offer increased statistical power. METHODS: Secondary analysis of a randomized controlled trial of CSA treated kidney transplant recipients with stable graft function assigned to receive 0.1 mg/kg/day TAC (target 5–8 ng/ml) or to continue CSA based immunosuppression (target 70–150 ng/ml) at a 2:1 ratio. Renal graft function was estimated via the MDRD (eGFR(MDRD)) and CKD-EPI (eGFR(CKD-EPI)) formulas. RESULTS: Forty-five patients continued CSA and 96 patients were converted to TAC with a median follow up of 24 months. Baseline demographics (except for recipient age) including native kidney disease, transplant characteristics, kidney graft function, medication use and comorbid conditions did not differ between groups. In respect to long-term renal graft function, linear mixed models showed significantly improved eGFR trajectories (eGFR(MDRD): p<0.001, eGFR(CKD-EPI): p<0.001) in the TAC versus CSA group over 24 months of follow up. Estimated eGFR(CKD-EPI) group differences between TAC and CSA were −3.49 (p = 0.019) at 3 months, −5.50 (p<0.001) at 12 months, and −4.48 ml/min/1.73m(2) (p = 0.003) at 24 months of follow up. Baseline eGFR was a significant predictor of eGFR trajectories (eGFR(MDRD): p<0.001, eGFR(CKD-EPI): p<0.001). Significant effects for randomization group were evident despite short-term trough levels in the supratherapeutic range (27% (n = 26) of TAC patients at week one). Median TAC trough levels were within target range at week 4 after conversion. CONCLUSION: Conversion of CSA treated kidney transplant recipients with stable graft function to TAC (target 5–8 ng/ml) showed significantly improved long-term eGFR trajectories when compared to CSA maintenance (target 70–150 ng/ml). TRIAL REGISTRATION: ClinicalTrials.gov NCT00182559 EudraCT identifier: 2004-004209-98 Public Library of Science 2015-08-13 /pmc/articles/PMC4535983/ /pubmed/26270340 http://dx.doi.org/10.1371/journal.pone.0135674 Text en © 2015 Plischke et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Plischke, Max Riegersperger, Markus Dunkler, Daniela Heinze, Georg Kikić, Željko Winkelmayer, Wolfgang C. Sunder-Plassmann, Gere Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title | Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title_full | Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title_fullStr | Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title_full_unstemmed | Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title_short | Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial |
title_sort | late conversion of kidney transplant recipients from ciclosporin to tacrolimus improves graft function: results from a randomized controlled trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535983/ https://www.ncbi.nlm.nih.gov/pubmed/26270340 http://dx.doi.org/10.1371/journal.pone.0135674 |
work_keys_str_mv | AT plischkemax lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT riegerspergermarkus lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT dunklerdaniela lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT heinzegeorg lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT kikiczeljko lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT winkelmayerwolfgangc lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial AT sunderplassmanngere lateconversionofkidneytransplantrecipientsfromciclosporintotacrolimusimprovesgraftfunctionresultsfromarandomizedcontrolledtrial |