Presentation Authors: Dijana Vitko*, Kohei Hasegawa, Boston, MA, Joseph W. McQuaid, Worcester, MA, Kylie H. Davis, Maggie R. Leary, Shannon E. DiMartino, Mansbach M. Jonathan, Richard S. Lee, Boston, MA
Introduction: Vesicoureteral reflux (VUR) predisposes children to urinary tract infection (UTI) associated kidney damage. Clinicians currently lack a comprehensive diagnostic method to help identify children with VUR who are at high-risk for UTIs and pyelonephritis, which frequently results in overtreatment with prophylactic antibiotics or surgery. We profiled changes in urinary metabolome in children with VUR and a history of UTI compared with control urine to identify metabolic pathways related to increased risk from UTI in VUR patients.
Methods: Urine was collected from VUR patients with history of single (n=41) and recurrent (n=44) UTIs, and age-matched pediatric controls (n=13). During sample collection patients had no active infection. Metabolome analysis was performed at Metabolon (Research Triangle Park, NC). Urine extracts were analyzed with 4 different liquid chromatography methods prior to mass spectrometry metabolome analysis. Reconstitution solvent for each sample contained a series of standards at fixed concentrations to ensure injection and chromatographic consistency. All samples were osmolality normalized prior to statistical analysis by ANOVA.
Results: Abundance of 175 and 157 metabolites significantly differed between the urine of VUR patients diagnosed with single and recurrent UTIs and pediatric controls (P < 0.05), respectively. Specifically, glycolysis and TCA-cycle intermediates were increased in single and recurrent UTI samples when compared with pediatric control samples, indicating increased energy production by the host cell or bacteria. In the children with UTI, we also found elevated metabolic products of amino acid degradation, particularly tryptophan catabolism suggestive of host inflammatory response and lymphocyte activation. Finally, we observed changes in bacterial metabolism metabolites from the glutamate degradation pathway and methyl-citrate cycle. Activation of these metabolic pathways after UTI resolution suggests ongoing bacterial metabolism or changes in bacterial species in patients with VUR.
Conclusions: We identified metabolomic changes indicative of host response and bacterial metabolism in the urine of patients with VUR and a history of UTIs. These changes will be further investigated as putative biomarkers to identify VUR patients at higher risk of UTIs.
Source of Funding: The Milton GrantHilary, Geoffrey, Reesa, and Rogan GroveSapna and Sat Shah