Mechanisms and treatment of cold-storage-induced microvascular obstructions in normothermic machine perfusion of human kidney

Human kidneys which were accepted for transplantation and subsequently not used were subjected to ex vivo normothermic machine perfusion. During perfusion it was found the tubular epithelia synthesized fibrinogen which led to red blood cell aggregation and pathologic plugging of renal microvasculature. Sequential ex vivo delivery of plasminogen and tissue plasminogen activator (tPA) during normothermic machine perfusion effectively lyses these fibrinogen-mediated plugs. Overall design: Pairs of human kidneys were subjected to ex vivo normothermic perfusion. One kidney in each pair was treated and the other not. Samples were taken pre- and post-perfusion for RNASeq.

本研究使用经器官移植评估合格但最终未被临床使用的人类肾脏，对其开展离体常温机器灌注（ex vivo normothermic machine perfusion）。灌注过程中观察到，肾小管上皮细胞可合成纤维蛋白原，进而引发红细胞聚集与肾脏微血管病理性堵塞。在常温机器灌注期间序贯输注纤溶酶原与组织型纤溶酶原激活剂（tPA），可有效溶解上述纤维蛋白原介导的微血管堵塞物。
实验设计方案：将成对的人类肾脏均进行离体常温机器灌注，每对肾脏中仅对其中一枚实施干预处理，另一枚作为对照。分别于灌注前及灌注后采集样本，进行RNA测序（RNASeq）。