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. Overall design: Perfused and unperfused snRNAseq samples from Mouse (3 perfused/3 unperfused), Pig (2 perfused/2 unperfused) and Rat (3 perfused / 3 unperfused).