Tyagi Pradeep, Tyagi Vikas, Qu Xianggui, Chuang Yao Chi, Kuo Hann-Chorng, Chancellor Michael
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
ERA's Lucknow Medical College, Lucknow, India;
Am J Physiol Renal Physiol. 2016 Sep 1;311(3):F548-54. doi: 10.1152/ajprenal.00213.2016. Epub 2016 Jun 22.
Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB.
膀胱过度活动症（OAB）和尿路感染（UTI）的症状重叠常常使诊断复杂化，并导致抗生素的过度处方。炎症反应是UTI和OAB的共同特征，在此我们假设尿液中炎症反应的分子差异有助于区分OAB和UTI。招募年龄在20 - 88岁之间的男女受试者进行这项尿液分析研究。62例UTI患者在抗生素治疗前尿试纸检测呈阳性，可获得尿液标本。其中6例患者在完成抗生素治疗后也提供了尿液。OAB队列（n = 59）和无症状对照组（n = 26）的受试者尿试纸检测呈阴性。通过MILLIPLEX MAP人细胞因子/趋化因子免疫测定法测量尿趋化因子，并通过单变量和多变量统计确定它们与UTI和OAB的关联。与OAB和无症状对照组相比，UTI患者中CXCL-1、CXCL-8（IL-8）和CXCL-10显著升高，同时IL-1A受体拮抗剂（sIL-1RA）水平降低。CXCL-1尿液水平升高预测UTI的比值比为1.018，特异性为80.77%，敏感性为59.68%。抗生素治疗后，所有CXC趋化因子均下降，CXCL-10显著下降。与OAB相比，CXCL-1和CXCL-10与UTI的强关联表明，与OAB中缺乏感染相比，UTI中驱动感染继发性炎症的信号通路存在机制差异。尿趋化因子突出了旁分泌信号传导中驱动UTI和OAB重叠症状的分子差异。
