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Background and objectives Hypothermic perfusion preservation is a technique used to minimize the risk of delayed graft function in kidney transplantation. However, the metabolic activity of kidneys during hypothermic perfusion and its modulation by oxygenation and pre-existing ischemic injury are not fully understood. This scoping review aims to summarize the current knowledge on kidney metabolism during hypothermic perfusion preservation. Materials and Methods A comprehensive search of PubMed, Embase, Web of Science, and Cochrane databases was conducted to identify relevant studies on kidney metabolism during hypothermic perfusion. Inclusion criteria encompassed papers reporting on metabolites in the perfusate or kidney tissue of animals or humans undergoing hypothermic perfusion. Data extraction and quality assessment were performed using predefined criteria. Results Out of 14,335 initially identified records, 52 were included. The majority of studies were conducted in animal models (48/52) [dog (26/52), pig (20/52), and rabbit (2/52)], with a smaller number involving human kidneys (7/52). Various perfusates, oxygenation levels, and kidney injury levels were used across the studies, leading to heterogeneity. A considerable risk of bias was identified in the reported studies. 11 papers utilized (non)radioactively labeled metabolites (tracers) to study metabolic pathways. Conclusions The reviewed studies demonstrate that kidneys remain metabolically active during hypothermic perfusion, irrespective of perfusion settings. Although tracers give us more insight into active metabolic pathways, kidney metabolism during hypothermic perfusion remains incompletely understood. Metabolism is influenced by perfusate composition, oxygenation levels, and likely also by pre-existing ischemic injury. In the modern era, with increasing donations after circulatory death and the emergence of hypothermic oxygenated perfusion, the focus should be on understanding metabolic perturbations caused by pre-existing injury levels and the effect of perfusate oxygen levels. The use of tracers is indispensable to understanding the kidney’s metabolism during perfusion, given the complexity of interactions between different metabolites.
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