Department of Pathology, The University of Hong Kong, Hong Kong, China.
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Clin Chim Acta. 2014 Sep 25;436:217-23. doi: 10.1016/j.cca.2014.05.014. Epub 2014 Jun 6.
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.
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.
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.
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.
尿路感染（UTI）是人类最常见的细菌感染之一；然而，目前还没有准确、快速的定量检测方法来诊断 UTI。尿试纸分析是半定量的，诊断准确性有限，而尿液培养虽然准确，但需要时间。我们描述了一种使用单一标志物诊断菌尿的定量生化方法。
我们使用（1）H NMR 光谱结合主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）比较了 88 例细菌性 UTI 患者和 61 例对照者的尿液代谢组。随后使用独立样本验证鉴定出的生物标志物。
尿液乙酸/肌酐（mmol/mmol）水平被确定为诊断细菌性 UTI 的最具鉴别性标志物，其曲线下面积-受体操作特征=0.97，最佳截断值为 0.03 mmol/mmol 时的灵敏度为 91%，特异性为 95%。为了验证，前瞻性招募了 60 个样本。使用最佳的乙酸/肌酐截断值，该方法的灵敏度为 96%，特异性为 94%，阳性预测值为 92%，阴性预测值为 97%，总准确率为 95%。该方法的诊断性能优于尿试纸分析或显微镜检查。此外，我们还观察到大肠杆菌相关 UTI 患者尿液中三甲基胺（TMA）水平升高。TMA 是哺乳动物-微生物共代谢物，高水平的 TMA 产生与细菌酶三甲基胺 N-氧化物（TMAO）还原酶有关，该酶将 TMAO 还原为 TMA。
尿液乙酸是一种被忽视的代谢物，可用于快速诊断 UTI，TMA 可用于 UTI 的病因诊断。随着 NMR 基于临床分析仪引入临床实验室，NMR 基于尿液分析可以转化为临床应用。
