3.5 Early kidney biomarkers of cisplatin-induced acute kidney
injury
Hierarchical clustering revealed that the majority of significantly
altered kidney metabolites were increased by cisplatin treatment, with
44/63 (69.8%) of metabolites being increased in C57BL/6 mice
(Figure 3C ) and 50/73 (68.5%) metabolites increased in FVB/N
mice (Figure S4C ). Creatine, p-cresol glucuronide, p-cresol
sulfate, phenylacetylglycine, phenylalanine, and tryptophan were found
to be elevated by cisplatin treatment in kidney tissue. Creatine showed
significant elevation throughout all four timepoints in FVB/N mice, and
similarly was also increased in C57BL/6 mice, though only significantly
increased at days 2 and 3 (Figure 6A, S7A ). P-cresol
glucuronide (Figure S7D ), p-cresol sulfate (Figure
S7E ), and phenylacetylglycine (Figure S7F ) were all
significantly elevated from day 2-4 in cisplatin-treated FVB/N kidneys.
These metabolites followed a similar pattern in C57BL/6 mice but were
significantly altered only at day 3 and 4 for p-cresol glucuronide and
sulfate (Figure 6D, 6E ), and days 1 and 4 for
phenylacetylglycine (Figure 6F ). Kidney levels of phenylalanine
(Figure 6G , S7G ) and tryptophan (Figure 6J,
S7J ) were also generally increased by cisplatin treatment, but only
tryptophan in C57BL/6 mice was shown to be significantly increased in
the early timepoints (Figure 6J ).
Equol 4-sulfate, LysoPC(20:3), proline betaine, and trigonelline were
kidney metabolites identified to be decreased by cisplatin treatment. In
kidneys from FVB/N mice, levels of equol 4-sulfate were significantly
decreased following cisplatin treatment for all timepoints
(Figure S7B ), and though equol 4-sulfate followed this
decreasing trend in C57BL/6 kidneys, none of the changes were
significant (Figure S7B ). Proline betaine was consistently
altered by cisplatin treatment in both strains, being significantly
decreased from days 2-4 (Figure 6H, S7H ). LysoPC(20:3) and
trigonelline were also significantly decreased from days 2-4 in
cisplatin-treated FVB/N mice (Figure S7C, S7I ). These
metabolites exhibited similar trends in C57BL/6 kidneys, though they
were only significantly altered on day 4 for both metabolites(Figure 6C, 6I ).