Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats.

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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

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

doi

10.1038/pr.2013.34

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

585-91

issue

5

eissn

0031-3998

issn

1530-0447

pii

pr201334

journal_volume

73

pub_type

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