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Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study

BACKGROUND. Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and qualit...

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Autores principales: Wang, Lu, Thompson, Emily, Bates, Lucy, Pither, Thomas L., Hosgood, Sarah A., Nicholson, Michael L., Watson, Christopher J.E., Wilson, Colin, Fisher, Andrew J., Ali, Simi, Dark, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447496/
https://www.ncbi.nlm.nih.gov/pubmed/32904032
http://dx.doi.org/10.1097/TXD.0000000000001046
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author Wang, Lu
Thompson, Emily
Bates, Lucy
Pither, Thomas L.
Hosgood, Sarah A.
Nicholson, Michael L.
Watson, Christopher J.E.
Wilson, Colin
Fisher, Andrew J.
Ali, Simi
Dark, John H.
author_facet Wang, Lu
Thompson, Emily
Bates, Lucy
Pither, Thomas L.
Hosgood, Sarah A.
Nicholson, Michael L.
Watson, Christopher J.E.
Wilson, Colin
Fisher, Andrew J.
Ali, Simi
Dark, John H.
author_sort Wang, Lu
collection PubMed
description BACKGROUND. Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and quality assessment before transplantation. This pilot study aimed to investigate the changes of FMN levels during normothermic reperfusion of kidneys, livers, and lungs and examine whether FMN could serve as a biomarker to predict posttransplant allograft quality. METHODS. FMN concentrations, in perfusates collected during NMP of kidneys, abdominal NRP, and ex vivo lung perfusion, were measured using fluorescence spectrometry and correlated to the available perfusion parameters and clinical outcomes. RESULTS. Among 7 transplanted kidneys out of the 11 kidneys that underwent NMP, FMN levels at 60 minutes of NMP were significantly higher in the allografts that developed delayed graft function and primary nonfunction (P = 0.02). Fifteen livers from 23 circulatory death donors that underwent NRP were deemed suitable for transplantation. Their FMN levels at 30 minutes of NRP were significantly lower than those not procured for transplantation (P = 0.004). In contrast, little FMN was released during the 8 lung perfusions. CONCLUSIONS. This proof of concept study suggested that FMN in the perfusates of kidney NMP has the potential to predict posttransplant renal function, whereas FMN at 30 minutes of NRP predicts whether a liver would be accepted for transplantation. More work is required to validate the role of FMN as a putative biomarker to facilitate safe and reliable decision-making before embarking on transplantation.
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spelling pubmed-74474962020-09-04 Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study Wang, Lu Thompson, Emily Bates, Lucy Pither, Thomas L. Hosgood, Sarah A. Nicholson, Michael L. Watson, Christopher J.E. Wilson, Colin Fisher, Andrew J. Ali, Simi Dark, John H. Transplant Direct Basic Science BACKGROUND. Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and quality assessment before transplantation. This pilot study aimed to investigate the changes of FMN levels during normothermic reperfusion of kidneys, livers, and lungs and examine whether FMN could serve as a biomarker to predict posttransplant allograft quality. METHODS. FMN concentrations, in perfusates collected during NMP of kidneys, abdominal NRP, and ex vivo lung perfusion, were measured using fluorescence spectrometry and correlated to the available perfusion parameters and clinical outcomes. RESULTS. Among 7 transplanted kidneys out of the 11 kidneys that underwent NMP, FMN levels at 60 minutes of NMP were significantly higher in the allografts that developed delayed graft function and primary nonfunction (P = 0.02). Fifteen livers from 23 circulatory death donors that underwent NRP were deemed suitable for transplantation. Their FMN levels at 30 minutes of NRP were significantly lower than those not procured for transplantation (P = 0.004). In contrast, little FMN was released during the 8 lung perfusions. CONCLUSIONS. This proof of concept study suggested that FMN in the perfusates of kidney NMP has the potential to predict posttransplant renal function, whereas FMN at 30 minutes of NRP predicts whether a liver would be accepted for transplantation. More work is required to validate the role of FMN as a putative biomarker to facilitate safe and reliable decision-making before embarking on transplantation. Lippincott Williams & Wilkins 2020-08-21 /pmc/articles/PMC7447496/ /pubmed/32904032 http://dx.doi.org/10.1097/TXD.0000000000001046 Text en Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Basic Science
Wang, Lu
Thompson, Emily
Bates, Lucy
Pither, Thomas L.
Hosgood, Sarah A.
Nicholson, Michael L.
Watson, Christopher J.E.
Wilson, Colin
Fisher, Andrew J.
Ali, Simi
Dark, John H.
Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title_full Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title_fullStr Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title_full_unstemmed Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title_short Flavin Mononucleotide as a Biomarker of Organ Quality—A Pilot Study
title_sort flavin mononucleotide as a biomarker of organ quality—a pilot study
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447496/
https://www.ncbi.nlm.nih.gov/pubmed/32904032
http://dx.doi.org/10.1097/TXD.0000000000001046
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