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Metabolomic Identification of Predictive and Early Biomarkers of Cisplatin-induced Acute Kidney Injury in Adult Head and Neck Cancer Patients
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  • Yong Jin Lim,
  • Steven Xiu,
  • M Kuruvilla,
  • Eric Winquist,
  • Stephen Welch,
  • Morgan Black,
  • Lauren Faught,
  • Jasmine Lee,
  • Michael (Guest Editor) Rieder,
  • Tom Blydt-Hansen,
  • Michael Zappitelli,
  • Brad Urquhart
Yong Jin Lim
Western University Schulich School of Medicine & Dentistry

Corresponding Author:[email protected]

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Steven Xiu
Western University Schulich School of Medicine & Dentistry
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M Kuruvilla
Western University Schulich School of Medicine & Dentistry
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Eric Winquist
Western University Schulich School of Medicine & Dentistry
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Stephen Welch
Western University Schulich School of Medicine & Dentistry
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Morgan Black
Western University Schulich School of Medicine & Dentistry
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Lauren Faught
Western University Schulich School of Medicine & Dentistry
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Jasmine Lee
SickKids Research Institute
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Michael (Guest Editor) Rieder
University of Western Ontario
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Tom Blydt-Hansen
British Columbia Children's Hospital
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Michael Zappitelli
SickKids Research Institute
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Brad Urquhart
Western University Schulich School of Medicine & Dentistry
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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.
13 Sep 2022Submitted to British Journal of Clinical Pharmacology
14 Sep 2022Submission Checks Completed
14 Sep 2022Assigned to Editor
28 Sep 2022Reviewer(s) Assigned
04 Dec 2022Review(s) Completed, Editorial Evaluation Pending
05 Dec 2022Editorial Decision: Revise Major
16 Dec 20221st Revision Received
19 Dec 2022Submission Checks Completed
19 Dec 2022Assigned to Editor
19 Dec 2022Review(s) Completed, Editorial Evaluation Pending
03 Jan 2023Editorial Decision: Accept