3.4 Early urine biomarkers of cisplatin-induced acute kidney injury
The vast majority of urinary metabolites were decreased following cisplatin treatment. Of 683 metabolites significantly altered by cisplatin treatment in C57BL/6 mice, 665 were decreased (97.3%,Figure 3B ), whereas 550/599 (91.8%) metabolites were decreased in FVB/N mice (Figure S4B ). Out of the identified metabolites, L-carnitine was the only metabolite increased by cisplatin treatment (Figure 5G, S6G ), and was consistently elevated in the urine of C57BL/6 mice from day 2-4 (Figure 5G ). In FVB/N mice, L-carnitine was also higher in the urine of cisplatin-treated mice throughout all timepoints, though only significant on day 1 (Figure S6G ).
Citric acid, equol, equol 7-O-glucuronide, homovanillic acid sulfate, indole-3-carboxaldehyde, indole-3-carboxylic acid, phenylpropionylglycine, pyrocatechol sulfate, succinate, trigonelline, and tyrosol 4-sulfate were all significantly decreased by cisplatin treatment. In both strains of mice, equol, equol 7-O-glucuronide, indole-3-carboxaldehyde, succinate, and trigonelline were all significantly lower in the cisplatin groups from days 2-4 (Figure 5, S6) . Citric acid, homovanillic acid sulfate, indole-3-carboxylic acid, phenylpropionylglycine, pyrocatechol sulfate, and tyrosol 4-sulfate showed a similar pattern, with decreased levels of these metabolites in cisplatin treated mice from days 2-4, albeit not achieving significance at all time points for both strains (Figure 5, S6 ).