SRS300 - A systematic review and proteomic meta-analysis to identify molecular targets for organ-directed treatment during normothermic ex vivo machine perfusion of the kidney

Abstract Background Normothermic machine perfusion (NMP) of the kidney represents an innovative approach to graft preservation, offering potential advantages over conventional storage solutions. Prolonged NMP has recently been shown to be safe and feasible, facilitating ex situ organ-directed treatment before transplantation. However, our understanding of which molecular targets are optimal remains relatively limited. Methods We conducted a systematic literature search to identify studies reporting an association between tissue-based proteomics and clinical outcomes following kidney transplantation (n = 7). Protein-level meta-analysis was performed to identify transcriptional programs underlying good and poor post-transplant outcomes. For the molecular targets identified, clinical feasibility was assessed by screening the literature for compatible pharmaceuticals. Results Genes can be up- or down-regulated in association with good or bad outcomes. TRRUST analysis maps observed patterns of gene activation to known transcription factor (TF) targets. We found 23 transcriptional programs significantly associated with post-transplant outcomes, including consistent upregulation of cell-protective TFs (NFE2L2) and downregulation of immune-related TFs (NFKB1 and RELA) in good outcome groups. Promising pharmaceutical candidates targeting these TF-governed pathways were identified, including nitric oxide, bardoxolone methyl, and tideglusib. Discussion The dysregulation of multiple transcriptional programs influences outcome following kidney transplantation. This identifies promising molecular targets for ex vivo organ-specific interventions during NMP. Several pharmaceutical agents can modulate these TFs and may serve as viable options for improving clinical results following kidney transplantation.