Metabolite enhanced perfusion solution improves kidney transplantation viability

Normothermic machine perfusion (NMP) has become a valuable tool to expand the pool of transplantable organs. However, the application of NMP to kidneys presents substantial challenges, mostly due to high variability in the configuration of perfusion buffers. Here we introduce a multimodal atlas of kidney cell injury associated with NMP using a literature-based consensus buffer. This resource provided the foundation for a systematic cross-species framework with integrated metabolic, genomic, spatial proteomic, and histopathologic profiling that was used to re-engineer the consensus perfusion buffer, mitigating cellular damage ex vivo and in vivo, thus extending organ viability and improving adequacy for transplantation.常温机器灌注（Normothermic Machine Perfusion, NMP）已成为扩充可移植器官储备库的重要工具。然而，将NMP应用于肾脏领域仍存在诸多显著挑战，这主要源于灌注缓冲液的配置方案存在高度异质性。本研究借助基于文献确立的共识灌注缓冲液，构建了与NMP相关的肾脏细胞损伤多模态图谱。该资源为系统性跨物种研究框架提供了支撑，通过整合代谢组学、基因组学、空间蛋白质组学及组织病理学多组学分析，完成了共识灌注缓冲液的重新优化，进而减轻了离体与体内的细胞损伤，最终延长了器官存活时长并提升了其移植适配性。