title: 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.
  
  
  CONCLUSIONS
  We conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin-induced AKI.
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
authors: Mina H
authors: MH
authors: Hanna
authors: Jeffrey L
authors: JL
authors: Segar
authors: Lynn M
authors: LM
authors: Teesch
authors: David C
authors: DC
authors: Kasper
authors: Franz S
authors: FS
authors: Schaefer
authors: Patrick D
authors: PD
authors: Brophy
mesh_terms: D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000652:urine*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007668:Kidney / Q000187:drug effects*; D013058:Mass Spectrometry; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000617:Aminoglycosides; D015415:Biomarkers