Metabolomic Identification of Predictive and Early Biomarkers of
Cisplatin-induced Acute Kidney Injury in Adult Head and Neck Cancer
Aim: Cisplatin causes acute kidney injury (AKI) in approximately
one-third of patients. Serum creatinine and urinary output are poor
markers of cisplatin-induced (AKI). Metabolomics was utilized to
identify predictive or early diagnostic biomarkers of cisplatin-induced
AKI. Methods: Thirty-one adult head and neck cancer patients receiving
cisplatin (dose ≥ 70 mg m2 -1) were recruited for metabolomics analysis.
Urine and serum samples were collected prior to cisplatin (pre), 24-48
hours after cisplatin (24-48h), and 5-14 days (post) after cisplatin.
Based on serum creatinine concentrations measured at the post timepoint,
11/31 patients were classified with clinical AKI. Untargeted
metabolomics was performed using liquid chromatography-mass
spectrometry. Results: Metabolic discrimination was observed between
“AKI” patients and “no AKI” patients at all timepoints. Urinary
glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid, and suberate
were significantly different between AKI patients and no AKI patients
prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate
were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid
and suberate were higher (3.62-fold and 1.91-fold) in AKI patients
relative to no AKI patients. Several urine and serum metabolites were
found to be altered 24-48 hours following cisplatin infusion,
particularly metabolites involved with mitochondrial energetics.
Conclusion: We propose glycine, hippuric acid sulfate,
3-hydroxydecanedioc acid, and suberate as predictive biomarkers of
predisposition to cisplatin-induced AKI. Metabolites indicative of
mitochondrial dysfunction may serve as early markers of subclinical AKI.