title: NMR-based metabolomic urinalysis: a rapid screening test for urinary tract infection.
abstract: BACKGROUND
  Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker.
  
  
  METHODS
  We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples.
  
  
  RESULTS
  The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA.
  
  
  CONCLUSIONS
  Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use.
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun-Yiu
authors.initials: CY
authors.lastname: Law
authors.affiliation: Research Centre of Infection and Immunology Hong Kong, China; State Key Laboratory for Emerging Infectious Diseases Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kelvin Kai-Wang
authors.initials: KK
authors.lastname: To
authors.affiliation: Research Centre of Infection and Immunology Hong Kong, China; State Key Laboratory for Emerging Infectious Diseases Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Stanley Kwok-Kuen
authors.initials: SK
authors.lastname: Cheung
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kim-Chung
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Research Centre of Infection and Immunology Hong Kong, China; State Key Laboratory for Emerging Infectious Diseases Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kong-Hung
authors.initials: KH
authors.lastname: Sze
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China.
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: Leung
authors.affiliation: Research Centre of Infection and Immunology Hong Kong, China; State Key Laboratory for Emerging Infectious Diseases Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D019342:Acetic Acid / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001437:Bacteriuria / Q000652:urine; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods* / Q000592:standards; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors; D016482:Urinalysis / Q000379:methods* / Q000592:standards; D014552:Urinary Tract Infections / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*
chemical_list: D019342:Acetic Acid
keywords: Acetic acid; Bacteriuria; NMR-based urinalysis; Trimethylamine; Urinary tract infection