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High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury

PURPOSE: Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI...

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Autores principales: Sikma, M. A., Hunault, C. C., van de Graaf, E. A., Verhaar, M. C., Kesecioglu, J., de Lange, D. W., Meulenbelt, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384949/
https://www.ncbi.nlm.nih.gov/pubmed/28132082
http://dx.doi.org/10.1007/s00228-017-2204-8
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author Sikma, M. A.
Hunault, C. C.
van de Graaf, E. A.
Verhaar, M. C.
Kesecioglu, J.
de Lange, D. W.
Meulenbelt, J.
author_facet Sikma, M. A.
Hunault, C. C.
van de Graaf, E. A.
Verhaar, M. C.
Kesecioglu, J.
de Lange, D. W.
Meulenbelt, J.
author_sort Sikma, M. A.
collection PubMed
description PURPOSE: Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI to whole-blood tacrolimus trough concentrations and other factors causing kidney injury. METHODS: We retrospectively studied kidney injury in 186 lung-transplantation patients at the UMC Utrecht between 2001 and 2011. Kidney function and whole-blood tacrolimus trough concentrations were determined from day 1 to 14 and at 1, 3, 6, and 12 months postoperative. Systemic inflammatory response syndrome (SIRS), septic shock, and nephrotoxic medications were evaluated as covariates for AKI. We analyzed liver injury and drug-drug interactions. RESULTS: AKI was present in 85 (46%) patients. Tacrolimus concentrations were supra-therapeutic in 135 of 186 patients (73%). AKI in the first week after transplantation was related to supra-therapeutic tacrolimus concentrations (OR 1.55; 95% CI 1.06–2.27), ≥3 other nephrotoxic drugs (OR 1.96; 95% CI 1.02–3.77), infection (OR 2.48; 95% CI 1.31–4.70), and cystic fibrosis (OR 2.17; 95% CI 1.16–4.06). Recovery rate of AKI was lower than expected (19%), and the cumulative incidence of severe CKD at 1 year was 15%. CONCLUSIONS: After lung transplantation, AKI is common and often evolves into severe CKD, which is a known cause of morbidity and mortality. Supra-therapeutic whole-blood tacrolimus trough concentrations are related to the early onset of AKI. Conscientious targeting tacrolimus blood concentrations might be vital in the early phase after lung transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-017-2204-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-53849492017-04-24 High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury Sikma, M. A. Hunault, C. C. van de Graaf, E. A. Verhaar, M. C. Kesecioglu, J. de Lange, D. W. Meulenbelt, J. Eur J Clin Pharmacol Pharmacokinetics and Disposition PURPOSE: Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI to whole-blood tacrolimus trough concentrations and other factors causing kidney injury. METHODS: We retrospectively studied kidney injury in 186 lung-transplantation patients at the UMC Utrecht between 2001 and 2011. Kidney function and whole-blood tacrolimus trough concentrations were determined from day 1 to 14 and at 1, 3, 6, and 12 months postoperative. Systemic inflammatory response syndrome (SIRS), septic shock, and nephrotoxic medications were evaluated as covariates for AKI. We analyzed liver injury and drug-drug interactions. RESULTS: AKI was present in 85 (46%) patients. Tacrolimus concentrations were supra-therapeutic in 135 of 186 patients (73%). AKI in the first week after transplantation was related to supra-therapeutic tacrolimus concentrations (OR 1.55; 95% CI 1.06–2.27), ≥3 other nephrotoxic drugs (OR 1.96; 95% CI 1.02–3.77), infection (OR 2.48; 95% CI 1.31–4.70), and cystic fibrosis (OR 2.17; 95% CI 1.16–4.06). Recovery rate of AKI was lower than expected (19%), and the cumulative incidence of severe CKD at 1 year was 15%. CONCLUSIONS: After lung transplantation, AKI is common and often evolves into severe CKD, which is a known cause of morbidity and mortality. Supra-therapeutic whole-blood tacrolimus trough concentrations are related to the early onset of AKI. Conscientious targeting tacrolimus blood concentrations might be vital in the early phase after lung transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-017-2204-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-01-28 2017 /pmc/articles/PMC5384949/ /pubmed/28132082 http://dx.doi.org/10.1007/s00228-017-2204-8 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Pharmacokinetics and Disposition
Sikma, M. A.
Hunault, C. C.
van de Graaf, E. A.
Verhaar, M. C.
Kesecioglu, J.
de Lange, D. W.
Meulenbelt, J.
High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title_full High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title_fullStr High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title_full_unstemmed High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title_short High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
title_sort high tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury
topic Pharmacokinetics and Disposition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384949/
https://www.ncbi.nlm.nih.gov/pubmed/28132082
http://dx.doi.org/10.1007/s00228-017-2204-8
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