5. CONCLUSION
Current clinical markers of AKI are incapable of detecting cisplatin-induced nephrotoxicity prior to the establishment of significant renal injury and functional impairment, and there is a need for biomarkers that are capable of earlier detection. In this study, a total of 26 plasma, urine, and kidney metabolites were identified as potential early biomarkers of cisplatin-induced acute kidney injury. Alterations in these metabolites over time following cisplatin administration were consistent in two separate strains of mice. These markers may help to better understand the pathophysiological mechanisms behind cisplatin nephrotoxicity and AKI in general. Many of these metabolites are indicative of dysregulated mitochondrial dysfunction, highlighting the detrimental effects of cisplatin on mitochondria. Many metabolites were dietary and gut-derived, indicating the need to investigate the crosstalk between the gut and the kidney in the setting of acute kidney injury. Our study provides a large panel of metabolites that can be targeted for future clinical studies of early detection of AKI and may provide guidance in the selection of therapeutic targets against cisplatin-induced nephrotoxicity. Further studies are necessary to validate the applicability, utility, and translatability of these metabolites in a clinical setting.