Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.
Transplantation. 2020 Sep;104(9):1825-1831. doi: 10.1097/TP.0000000000003323.
The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation.
To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury.
Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury.
ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.
器官短缺是一个日益严重的问题。通过使用循环死亡后的器官（死后循环供体 [DCD]）来增加器官供应。然而，由于长时间的热缺血时间和缺乏可靠的肾脏活力测量方法，许多 DCD 移植物被丢弃。质子磁共振波谱（pMRI）是一种非侵入性方法，可检测高能磷酸盐代谢物，如 ATP。因此，pMRI 可以在移植前预测肾脏的能量状态及其活力。
为了模拟 DCD，猪的肾脏在低温机器灌注前经历 0、30 或 60 分钟的热缺血。在体外灌注过程中，我们使用 pMRI 评估能量代谢物。此外，我们还进行了钆灌注序列。每个样本都进行了组织病理学分析和评分。能量状态和肾脏灌注与肾脏损伤相关。
使用 pMRI，我们发现猪肾脏在有氧（100 kPa）条件下迅速产生 ATP，直到 22 小时仍保持稳定。30 分钟和 60 分钟的热缺血会导致明显的组织学损伤，延迟皮质和髓质的钆清除（灌注），并降低 ATP 水平，但不降低其前体（AMP）。最后，ATP 水平和肾脏灌注均与肾脏组织学损伤的严重程度呈负相关。
使用 pMRI 测量的 ATP 水平和肾脏灌注是热缺血后肾脏损伤的生物标志物。未来的工作将确定 pMRI 在预测肾脏移植物和患者生存方面的作用。
