3.3 Predictive and early urinary markers of cisplatin-induced acute kidney injury
In urine, glycine, 3-hydroxydecanedioc acid, hippuric acid sulfate, and suberate were found to be significantly different between no AKI and AKI patients prior to cisplatin infusion (Figure 3 ). Levels of hippuric acid sulfate were 8.85-fold and 9.08-fold lower in the AKI group compared to the no AKI group at the pre and 24-48h timepoints, respectively (Table 2 , Figure 3C, 3E ). 3-hydroxydecanedioc acid and suberate were significantly higher in AKI patients compared to no AKI patients at the pre timepoint (3.62-fold and 1.91-fold, respectively) and trended towards being higher at the 24-48h timepoint (1.98-fold and 1.82-fold, respectively), though the difference was not significant (Table 2 , Figure 3B, 3D ). Finally, glycine levels were 2.22-fold and 2.55-fold lower in AKI patients relative to no AKI patients at the pre and post timepoints, respectively (Table 2, Figure 3A ). Diagnostic performance of the markers was assessed by calculation of AUROC. AUROC values ≥ 0.7 are generally considered to be acceptable discrimination. Though serum creatinine was an excellent discriminatory marker of no AKI vs. AKI at the post timepoint (AUROC of 0.947), it performed poorly (AUROC < 0.7) at the pre and 24-48h timepoints (Figure 3F ). Glycine, 3-hydroxydecanedioc acid, hippuric acid sulfate, and suberate all had AUROC > 0.7 at the pre timepoint, with suberate exhibiting the strongest performance (AUROC > 0.8). These metabolites, with the exception of glycine, also had AUROC > 0.7 at the 24-48h timepoint, with hippuric acid sulfate and suberate possessing AUROC > 0.8.