*Purpose: The kidney is a highly metabolic organ and lipids are an important energy source. In this study, we examined the lipid profiles of discarded human kidneys placed on ex vivo normothermic perfusion (EVNP) to discern trends in lipid metabolites and associations with renal function.

*Methods: Eight human kidneys deemed unsuitable for transplantation were placed on EVNP with oxygenated packed red blood cells for 12 hours. Markers of kidney perfusion, function, and injury were monitored, and tissue samples were obtained for lipid metabolomics analysis (lipidomics).

*Results: Two groups emerged with 4 kidneys termed “good performers” and the other 4 kidneys termed “poor performers,” where the former group compared to the latter had higher urine output (69.0 vs 10.3 ml/30 min, respectively), higher renal flow, lower resistance, and lower urinary neutrophil gelatinase-associated lipocalin (NGAL) (Figure 1). The good performers had lower baseline triglyceride levels that slightly increased in the first 30 minutes of EVNP, followed by a large increase up to 6-8 hours. The poor performers had higher baseline triglyceride levels with a decrease in the first 30 minutes of EVNP, followed by a gradual increase (Figure 2). Overall, triglycerides decreased while long-chain acylcarnitines increased during the first 30 minutes, which may represent early triglyceride mobilization to yield fatty acids and in turn, acylcarnitines. In addition, the good performers had lower baseline ceramide levels followed by a decrease in the first 30 minutes, while poor performers demonstrated the opposite. As ceramides are a metabolite implicated in mitochondrial dysfunction, this may suggest that the poor performers had markers of increased cellular toxicity.

*Conclusions: High-risk kidneys not acceptable for transplantation displayed different levels of function on EVNP coincident with alterations in tissue lipid profiles. Our findings suggest that kidneys destined to perform poorly on EVNP have higher baseline triglycerides and ceramides, which may be indicative of abnormal metabolism in the tissue.

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