(A) Tissue analysis after MEPS perfusion was performed using histopathology and pathology-oriented multiplexed imaging. (B) Histopathology showed partial reversal of deleterious effects seen with consensus buffer. Scale bar: 10 μm. TUNEL staining revealed significantly reduced apoptosis after MEPS perfusion. Scale bar: 30 μm. Data are shown as median with 95% CI. Unpaired student’s t test was used for statistical analysis. (C) Overview over the targets for multiplexed imaging. (D) Pixel-based cluster analysis identified 27 individual clusters. Scale bar: 50 μm. (E) Cluster 14 was defined by its top contributors, including Megalin, p62 (ubiquitin-binding protein 62), CalR, and LTL and provides a clear example of cellular processes preserved by MEPS. Data are presented as median with 95% CI. Scale bar: 50 μm. Brown-Forsythe and Welch ANOVA were used for statistical analysis. (F) Using the clusters, immediate proximity analysis predicted deleterious mitochondrial signals to negatively affect metabolism in PTs after NMP with consensus buffer but not with MEPS. (G) In summary, MEPS perfusion improved metabolite supply, reduced ER-and mitochondrial stress, and led to transcriptional regulation and spatial protein modulation, which in turn resulted in preserved organ viability. AP-1, Activating protein-1; BM, Basement membrane; CD, Collecting duct; CD41, Cluster of differentiation 41; ER met, Metabolism of the ER; Fib, Fibroblast; Leuk, Leucocyte; Mito, Mitochondria; Nuc, Nucleus; Podo, Podocyte; Prolif, Proliferation; PT, Proximal tubule; STAT3, Signal transducer and activator of transcription 3; TAL, Thick ascending limb of the Loop of Henle.