NMR-based metabolomic urinalysis: A rapid screening test for urinary tract infection

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 ¹H 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.