Ex vivo warm kidney perfusion is associated with extensive metabolic derangements

Ex vivo warm perfusion is a promising method for pre-transplant viability assessment and resuscitation of deceased-donor kidneys. To realize the full potential of warm perfusion, understanding ex vivo kidney metabolism, and how it differs from in vivo metabolism, is essential. Here, we show that ex vivo kidney metabolism differs substantially from in vivo conditions. Using metabolomics, transcriptomics, and proteomics, we show that ex vivo warm kidney perfusion leads to enhanced glycolysis, decreased gluconeogenesis, and impaired tricarboxylic acid cycle activity, all with NAD+ depletion as a common denominator. This depletion is associated with enhanced immune responses and cell death processes, and is exacerbated by ischemic injury. Furthermore, we identified metabolic biomarkers that differentiate between injured and healthy donor kidneys.This study revealed metabolic alterations that should be considered when optimizing ex vivo warm perfusion strategies to support pre-transplant organ resuscitation and viability assessment.