Biomarkers in Ex Vivo Kidney Perfusion: A Shift Toward Omics Diagnostics

There is a need for more accurate viability assessment of donor kidneys before transplantation. Ex vivo machine perfusion provides a dynamic platform for such evaluation and is increasingly used to support organ selection. Numerous traditional biomarkers, such as perfusion parameters and injury markers, have been proposed, but their predictive value remains limited. These markers are mostly validated in the in vivo setting and may not hold the same relevance during ex vivo perfusion, where physiology is fundamentally different. Furthermore, interpretation is complicated by variables such as perfusion temperature, duration, perfusate, and device-specific settings. To date, no single biomarker during machine perfusion can guide clinical decision-making. Molecular profiling offers a promising strategy to overcome the limitations of traditional markers. While traditional biomarkers typically reflect late-stage damage or narrow aspects of cell injury, transcriptomic, proteomic, and metabolomic techniques allow detection of early, system-wide responses to ischemia and reperfusion. The use of these methods during machine perfusion can reveal multilayered signatures of injury, stress, and metabolic adaptation before transplantation. This review briefly discusses traditional biomarkers and elaborates on recent molecular studies performed during ex vivo kidney perfusion. Findings from preclinical studies include upregulation of inflammatory signaling, oxidative stress responses, cytoskeletal remodeling, and mitochondrial dysfunction. Although largely observational, emerging data suggest that certain molecular patterns may correlate with injury and posttransplant outcomes. Despite the need for clinical validation, molecular profiling during machine perfusion could enable more objective assessment of graft viability. A shift toward mechanistic, multi-omic approaches may support more standardized, biologically informed decision-making.