Utilization of kidneys from extended criteria donors leads to an increase in average warm ischemia time (WIT), which is associated\nwith larger degrees of ischemia-reperfusion injury (IRI). Kidney resuscitation by extra corporeal perfusion in situ allows up to 60\nminutes of asystole after the circulatory death.Molecular studies of kidney grafts from human donors with critically expanded WIT\nare warranted. Transcriptomes of two human kidneys from two different donors were profiled after 35-45minutes of WIT and after\n120 minutes of normothermic perfusion and compared. Baseline gene expression patterns in ischemic grafts display substantial\nintrinsic differences. IRI does not lead to substantial change in overall transcription landscape but activates a highly connected\nprotein network with hubs centered on Jun/Fos/ATF transcription factors and HSP1A/HSPA5 heat shock proteins. This response\nis regulated by positive feedback. IRI networks are enriched in soluble proteins and bio fluids assayable substances, thus, indicating\nfeasibility of the longitudinal, minimally invasive assessment in vivo. Mapping of IRI related molecules in ischemic and re per fused\nkidneys provides a rationale for possible organ conditioning during machine assisted ex vivo normothermic perfusion. A study of\nnatural diversity of the transcriptional landscapes in presumably normal, transplantation-suitable human organs is warranted.
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