title: Alterations in urinary metabolites due to unilateral ureteral obstruction in a rodent model.
abstract: Urinary tract obstruction (UTO) results in renal compensatory mechanisms and may progress to irrecoverable functional loss and histologic alterations. The pathophysiology of this progression is poorly understood. We identified urinary metabolite alterations in a rodent model of partial and complete UTO using (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy. Principal component analysis (PCA) was used for classification and discovery of differentiating metabolites. UTO was associated with elevated urinary levels of alanine, succinate, dimethylglycine (DMG), creatinine, taurine, choline-like compounds, hippurate, and lactate. Decreased urinary levels of 2-oxoglutarate and citrate were noted. The patterns of alteration in partial and complete UTO were similar except that an absence of elevated urinary osmolytes (DMG and hippurate) was noted in complete UTO. This pattern of metabolite alteration indicates impaired oxidative metabolism of the mitochondria in renal proximal tubules and production of renal protective osmolytes by the medulla. Decreased production of osmolytes in complete obstruction better elucidates the pathophysiology of progression from renal compensatory mechanisms to irrecoverable changes. Further confirmation of these potential biomarkers in children with UTO is necessary.
authors.affiliation: Department of Urology, Dalhousie University, Canada. dawn.maclellan@iwk.nshealth.ca
authors.forename: Dawn L
authors.initials: DL
authors.lastname: MacLellan
authors.forename: Diane
authors.initials: D
authors.lastname: Mataija
authors.forename: Alan
authors.initials: A
authors.lastname: Doucette
authors.forename: Weei
authors.initials: W
authors.lastname: Huang
authors.forename: Chantale
authors.initials: C
authors.lastname: Langlois
authors.forename: Greg
authors.initials: G
authors.lastname: Trottier
authors.forename: Ian W
authors.initials: IW
authors.lastname: Burton
authors.forename: John A
authors.initials: JA
authors.lastname: Walter
authors.forename: Tobias K
authors.initials: TK
authors.lastname: Karakach
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D009994:Osmolar Concentration; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014517:Ureteral Obstruction / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000652:urine*
chemical_list: D003404:Creatinine