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.