PDF(Pubmed)
Abstract：
UNASSIGNED: The gap between available donor grafts and patients on the waiting lists is constantly growing. This leads to an increased utilization of high-risk and therefore more vulnerable kidney grafts. The use of high-risk organs requires further optimization of machine preservation and assessment strategies before transplantation. Hypothermic machine perfusion (HMP) is the standard of care for kidneys originating from donation after circulatory death (DCD), whereas the evidence of HMP with additional oxygen (HOPE) is still very limited. Furthermore, an objective quality assessment of HMP-perfused kidneys is lacking. Recently, the release of mitochondria derived fragments, i.e., flavin mononucleotide (FMN) of complex I during machine liver perfusion was shown to be predictive for liver graft function before implantation. Therefore, the aim of this study was to evaluate, if FMN is useful also for assessment of kidney injury before use.
UNASSIGNED: A porcine perfusion model was used to investigate the feasibility of assessment of kidney grafts during hypothermic oxygenated perfusion (HOPE) with either 0, 30 or 60 minutes of warm ischemia. The model with warm ischemia times (WIT) of 30 min and 60 min, was used to mimic a clinically relevant scenario. A group with no warm ischemia time (0\' WIT) served as control group. The groups underwent minimal static cold storage (SCS) of 2 h followed by 2 h of end-ischemic HOPE with repeated real-time FMN measurements. In a further step, these values were related to the release of damage-associated molecular patterns (DAMPs) and to the functionality of the respiratory chain, represented by the capacity of ATP production.
UNASSIGNED: We demonstrate, first, feasibility of perfusate FMN measurements in perfused kidneys, and secondly its correlation with donor warm ischemia time. Accordingly, FMN measurement showed significantly higher release in the 60-minute WIT group (n = 4) compared to the 30-minute WIT (n = 4) and the control group (n = 4). FMN release correlated also with DAMP signaling, such as the release of 8-OHdG and HMGB1. Finally, ATP replenishment proved to be best in control kidneys, followed by kidneys with 30 min and then by kidneys with 60 min of WIT.
UNASSIGNED: This study demonstrates the feasibility of FMN measurement in kidneys during HOPE. In addition, we show a correlation between FMN quantification and pre-existing kidney graft injury. Based on this, real-time FMN measurement during HOPE may be an objective assessment tool to accept high-risk kidneys for transplantation while minimizing post-transplant dysfunction, moving away from former \"gut feeling\" towards objective criteria in accepting marginal kidney grafts for transplantation. Graft evaluation based on these results may close the gap between available grafts and patients on the waiting lists by increasing utilization rates without significant impact for the recipients.
UNASSIGNED: A porcine perfusion model was used to investigate the feasibility of assessment of kidney grafts during hypothermic oxygenated perfusion (HOPE) with either 0, 30 or 60 minutes of warm ischemia. The model with warm ischemia times (WIT) of 30 min and 60 min, was used to mimic a clinically relevant scenario. A group with no warm ischemia time (0\' WIT) served as control group. The groups underwent minimal static cold storage (SCS) of 2 h followed by 2 h of end-ischemic HOPE with repeated real-time FMN measurements. In a further step, these values were related to the release of damage-associated molecular patterns (DAMPs) and to the functionality of the respiratory chain, represented by the capacity of ATP production.
UNASSIGNED: We demonstrate, first, feasibility of perfusate FMN measurements in perfused kidneys, and secondly its correlation with donor warm ischemia time. Accordingly, FMN measurement showed significantly higher release in the 60-minute WIT group (n = 4) compared to the 30-minute WIT (n = 4) and the control group (n = 4). FMN release correlated also with DAMP signaling, such as the release of 8-OHdG and HMGB1. Finally, ATP replenishment proved to be best in control kidneys, followed by kidneys with 30 min and then by kidneys with 60 min of WIT.
UNASSIGNED: This study demonstrates the feasibility of FMN measurement in kidneys during HOPE. In addition, we show a correlation between FMN quantification and pre-existing kidney graft injury. Based on this, real-time FMN measurement during HOPE may be an objective assessment tool to accept high-risk kidneys for transplantation while minimizing post-transplant dysfunction, moving away from former \"gut feeling\" towards objective criteria in accepting marginal kidney grafts for transplantation. Graft evaluation based on these results may close the gap between available grafts and patients on the waiting lists by increasing utilization rates without significant impact for the recipients.
摘要：
■可用的供体移植物与等待名单上的患者之间的差距在不断扩大。这导致高风险和因此更脆弱的肾移植物的利用增加。使用高风险器官需要在移植前进一步优化机器保存和评估策略。低温机器灌注（HMP）是循环系统死亡（DCD）后捐献的肾脏护理标准，而HMP与额外的氧气（希望）的证据仍然非常有限。此外，缺乏对HMP灌注肾脏的客观质量评估.最近,线粒体衍生片段的释放，即，在机器肝脏灌注期间，复合物I的黄素单核苷酸（FMN）被证明可以预测植入前的肝移植功能。因此,这项研究的目的是评估，如果FMN在使用前也可用于评估肾损伤。
■使用猪灌注模型来研究在0、30或60分钟的热缺血的低温氧合灌注（HOPE）期间评估肾移植物的可行性。热缺血时间(WIT)分别为30min和60min,用于模拟临床相关场景。无热缺血时间（0'WIT）的组作为对照组。两组进行2小时的最小静态冷藏（SCS），然后进行2小时的末端缺血HOPE，并重复进行实时FMN测量。在进一步的步骤中,这些值与损伤相关分子模式（DAMPs）的释放和呼吸链的功能有关，以ATP生产能力为代表。
■我们演示，首先,在灌注肾脏中测量灌注液FMN的可行性，其次与供体热缺血时间有关。因此，与30分钟WIT（n=4）和对照组（n=4）相比，FMN测量显示60分钟WIT组（n=4）的释放明显更高。FMN释放也与DAMP信号相关，如释放8-OHdG和HMGB1。最后,ATP补充在控制肾脏中被证明是最好的，然后是30分钟的肾脏，然后是60分钟的WIT肾脏。
■这项研究证明了HOPE期间肾脏中FMN测量的可行性。此外,我们显示了FMN定量与预先存在的肾移植物损伤之间的相关性。基于此,HOPE期间的实时FMN测量可能是一种客观的评估工具，可以接受高风险肾脏进行移植，同时最大程度地减少移植后的功能障碍，从以前的“直觉”转向接受边缘肾移植移植的客观标准。基于这些结果的移植物评估可以通过提高利用率来缩小可用移植物与等待名单上的患者之间的差距，而不会对接受者产生重大影响。
■使用猪灌注模型来研究在0、30或60分钟的热缺血的低温氧合灌注（HOPE）期间评估肾移植物的可行性。热缺血时间(WIT)分别为30min和60min,用于模拟临床相关场景。无热缺血时间（0'WIT）的组作为对照组。两组进行2小时的最小静态冷藏（SCS），然后进行2小时的末端缺血HOPE，并重复进行实时FMN测量。在进一步的步骤中,这些值与损伤相关分子模式（DAMPs）的释放和呼吸链的功能有关，以ATP生产能力为代表。
■我们演示，首先,在灌注肾脏中测量灌注液FMN的可行性，其次与供体热缺血时间有关。因此，与30分钟WIT（n=4）和对照组（n=4）相比，FMN测量显示60分钟WIT组（n=4）的释放明显更高。FMN释放也与DAMP信号相关，如释放8-OHdG和HMGB1。最后,ATP补充在控制肾脏中被证明是最好的，然后是30分钟的肾脏，然后是60分钟的WIT肾脏。
■这项研究证明了HOPE期间肾脏中FMN测量的可行性。此外,我们显示了FMN定量与预先存在的肾移植物损伤之间的相关性。基于此,HOPE期间的实时FMN测量可能是一种客观的评估工具，可以接受高风险肾脏进行移植，同时最大程度地减少移植后的功能障碍，从以前的“直觉”转向接受边缘肾移植移植的客观标准。基于这些结果的移植物评估可以通过提高利用率来缩小可用移植物与等待名单上的患者之间的差距，而不会对接受者产生重大影响。
