Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats

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: 3 days old rats were divided into 3 groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/day for 7 days. Urine and blood were collected after 3 and 7days 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 gentamicin doses, urinary tryptophan was significantly (p<0.05) increased; fold change (1.91 and 2.31 after 3d, 1.81and 1.93 after 7d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (p<0.05) decrease, fold change (0.26 and 0.24 after 3d, 0.21 and 0.52 after 7d), suggesting 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.