Patel Kamlesh, Nath Jay, Smith Thomas, Darius Tom, Thakker Alpesh, Dimeloe Sarah, Inston Nicholas, Ready Andrew, Ludwig Christian
Department of Renal Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Transplant Direct. 2024 Dec 10;11(1):e1736. doi: 10.1097/TXD.0000000000001736. eCollection 2025 Jan.
The provision of a metabolic substrate is one mechanism by which hypothermic machine perfusion (HMP) of kidneys provides clinical benefit. This study aimed to describe metabolism in ex vivo human kidneys undergoing HMP before transplantation using C-labeled glucose as a metabolic tracer.
Cadaveric human kidneys were perfused with modified clinical-grade perfusion fluid (kidney perfusion solution [KPS-1], Organ Recovery Systems), in which glucose was uniformly enriched with the stable isotope C ([U-C] glucose). The sampled perfusion fluid was analyzed using a blood gas analyzer, and metabolic profiling was performed using 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Functional outcome measures included serum creatinine levels and the development of delayed graft function.
Fourteen kidneys were perfused with the modified KPS-1 and successfully transplanted. The mean duration of HMP was 8.7 h. There was a sustained increase in the conversion of glucose into glycolytic end products, such as lactate, in donor kidneys during HMP. There was no significant association between functional outcomes and metabolism during the HMP. anaerobic metabolism was indicated by continuing lactate production, as indicated by increasing concentrations of universally C-labeled lactate ([U-C] lactate) in perfusion fluid from all kidneys. This was more evident in donation after circulatory death donor kidneys.
Our study is the first to use [U-C] glucose to describe the metabolism during HMP. The consequences of an initial warm ischemic insult on circulatory death in donor kidneys continue during the preservation period.
提供代谢底物是肾脏低温机器灌注（HMP）产生临床益处的一种机制。本研究旨在使用C标记的葡萄糖作为代谢示踪剂，描述移植前接受HMP的离体人肾的代谢情况。
用改良的临床级灌注液（肾脏灌注溶液[KPS-1]，器官回收系统）灌注尸体人肾，其中葡萄糖均匀富集稳定同位素C（[U-C]葡萄糖）。使用血气分析仪分析采集的灌注液，并使用一维和二维核磁共振光谱以及质谱进行代谢谱分析。功能结局指标包括血清肌酐水平和移植肾功能延迟恢复的发生情况。
14个肾脏用改良的KPS-1灌注并成功移植。HMP的平均持续时间为8.7小时。在HMP期间，供体肾脏中葡萄糖向糖酵解终产物（如乳酸）的转化持续增加。HMP期间功能结局与代谢之间无显著关联。所有肾脏灌注液中普遍C标记的乳酸（[U-C]乳酸）浓度增加表明，持续的乳酸产生提示存在无氧代谢。这在心脏死亡后供体肾脏中更为明显。
我们的研究首次使用[U-C]葡萄糖来描述HMP期间的代谢情况。供体肾脏最初的热缺血损伤对心脏死亡的影响在保存期内持续存在。
