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黄素单核苷酸作为器官质量生物标志物的初步研究

Flavin Mononucleotide as a Biomarker of Organ Quality-A Pilot Study.

作者信息

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

机构信息

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Department of Surgery, University of Cambridge, Cambridge, United Kingdom.

出版信息

Transplant Direct. 2020 Aug 21;6(9):e600. doi: 10.1097/TXD.0000000000001046. eCollection 2020 Sep.

Abstract

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 ( = 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 ( = 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.

摘要

背景

在低温肝脏灌注过程中,从受损的线粒体复合体I释放出来的黄素单核苷酸(FMN)已被证明可预测90天移植肝丢失情况。常温机器灌注(NMP)和常温区域灌注(NRP)用于移植前的器官修复和质量评估。这项前瞻性研究旨在调查肾脏、肝脏和肺脏常温再灌注期间FMN水平的变化,并检验FMN是否可作为预测移植后同种异体移植物质量的生物标志物。

方法

使用荧光光谱法测量在肾脏NMP、腹部NRP和离体肺灌注期间收集的灌注液中的FMN浓度,并将其与可用的灌注参数和临床结果相关联。

结果

在接受NMP的11个肾脏中,有7个被移植。发生移植功能延迟和原发性无功能的同种异体移植物在NMP 60分钟时的FMN水平显著更高(=0.02)。23例循环性死亡供体的15个肝脏接受了NRP,被认为适合移植。它们在NRP 30分钟时的FMN水平显著低于未进行移植的肝脏(=0.004)。相比之下,在8次肺灌注期间释放的FMN很少。

结论

这项概念验证研究表明,肾脏NMP灌注液中的FMN有可能预测移植后的肾功能,而NRP 30分钟时的FMN可预测肝脏是否会被接受用于移植。在将FMN作为一种假定的生物标志物以促进移植前安全可靠的决策制定方面,还需要更多的工作来验证其作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f02/7447496/c212cae46f80/txd-6-e600-g001.jpg

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