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Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats. Pediatr Res 2013 May;73(5):585-91

Date

02/16/2013

Pubmed ID

23411940

Pubmed Central ID

PMC3640567

DOI

10.1038/pr.2013.34

Scopus ID

2-s2.0-84878301277   26 Citations

Abstract

BACKGROUND: Aminoglycoside exposure is a common cause of acute kidney injury (AKI). Delay in the diagnosis of AKI using conventional biomarkers has been one of the important obstacles in applying early effective interventions. We tested the hypothesis that urinary metabolomics could identify novel early biomarkers for toxic renal injury.

METHODS: Three-day-old rats were divided into three groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/d for 7 d. Urine and blood were collected after 3 and 7 d of injections. Urinary metabolites were evaluated using high-performance liquid chromatography and gas chromatography/mass spectrometry.

RESULTS: A distinct urinary metabolic profile characterized by glucosuria, phosphaturia, and aminoaciduria was identified preceding changes in serum creatinine. At both the gentamicin doses, urinary tryptophan was significantly (P < 0.05) increased (fold change: 1.91 and 2.31 after 3 d; 1.81 and 1.93 after 7 d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (P < 0.05) decrease (fold change: 0.26 and 0.24 after 3 d; 0.21 and 0.52 after 7 d), suggesting an interruption of the normal tryptophan metabolism pathway.

CONCLUSION: We conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin-induced AKI.

Author List

Hanna MH, Segar JL, Teesch LM, Kasper DC, Schaefer FS, Brophy PD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aminoglycosides
Animals
Animals, Newborn
Biomarkers
Chromatography, Gas
Chromatography, High Pressure Liquid
Female
Kidney
Mass Spectrometry
Metabolomics
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00