ABSTRACT
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.