Yu Wan-Ru, Jiang Yuan-Hong, Jhang Jia-Fong, Kuo Hann-Chorng
Department of Nursing, Hualien Tzu Chi Hospital, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan.
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.
Int J Mol Sci. 2023 Jul 27;24(15):12055. doi: 10.3390/ijms241512055.
To analyze the urinary biomarkers in men with lower urinary-tract symptoms (LUTS) and identify interstitial cystitis/bladder pain syndrome (IC/BPS) from the other lower urinary-tract dysfunctions (LUTDs) by the levels of characteristic urinary biomarkers. In total, 198 men with LUTS were prospectively enrolled and urine samples were collected before intervention or medical treatment. Videourodynamic studies were routinely performed and the LUTDs were diagnosed as having bladder-outlet obstruction (BOO) such as bladder-neck dysfunction, benign prostatic obstruction, or poor relaxation of external sphincter (PRES); and bladder dysfunction such as detrusor overactivity (DO), hypersensitive bladder (HSB), and IC/BPS. Patients suspicious of IC/BPS were further confirmed by cystoscopic hydrodistention under anesthesia. The urine samples were investigated for 11 urinary inflammatory biomarkers including eotaxin, IL-6, IL-8, CXCL10, MCP-1, MIP-1β, RANTES, TNF-α, NGF, BDNF, and PGE2; and 3 oxidative stress biomarkers 8-OHdG, 8-isoprostane, and TAC. The urinary biomarker levels were analyzed between LUTD subgroups and IC/BPS patients. The results of this study revealed that among the patients, IC/BPS was diagnosed in 48, BOO in 66, DO in 25, HSB in 27, PRES in 15, and normal in 17. Patients with BOO had a higher detrusor pressure and BOO index than IC/BPS, whereas patients with IC/BPS, BOO, and DO had a smaller cystometric bladder capacity than the PRES and normal subgroups. Among the urinary biomarkers, patients with IC/BPS had significantly higher levels of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC than all other LUTD subgroups. By a combination of different characteristic urinary biomarkers, TNF-α, and eotaxin, either alone or in combination, had the highest sensitivity, specificity, positive predictive value, and negative predictive value to discriminate IC/BPS from patients of all other LUTD subgroups, BOO, DO, or HSB subgroups. Inflammatory biomarker MCP-1 and oxidative stress biomarkers 8-OHdG and TAC, although significantly higher in IC/BPS than normal and PRES subgroups, did not have a diagnostic value between male patients with IC/BPS and the BOO, DO, or HSB subgroups. The study concluded that using urinary TNF-α and eotaxin levels, either alone or in combination, can be used as biomarkers to discriminate patients with IC/BPS from the other LUTD subgroups in men with LUTS.
分析下尿路症状（LUTS）男性患者的尿液生物标志物，并通过特征性尿液生物标志物水平，从其他下尿路功能障碍（LUTD）中鉴别出间质性膀胱炎/膀胱疼痛综合征（IC/BPS）。总共前瞻性纳入了198例LUTS男性患者，并在干预或药物治疗前采集尿液样本。常规进行视频尿动力学检查，将LUTD诊断为膀胱出口梗阻（BOO），如膀胱颈功能障碍、良性前列腺梗阻或外括约肌松弛不良（PRES）；以及膀胱功能障碍，如逼尿肌过度活动（DO）、膀胱过敏（HSB）和IC/BPS。疑似IC/BPS的患者在麻醉下通过膀胱镜水扩张进一步确诊。对尿液样本检测了11种尿液炎症生物标志物，包括嗜酸性粒细胞趋化因子、IL-6、IL-8、CXCL10、MCP-1、MIP-1β、RANTES、TNF-α、NGF、BDNF和PGE2；以及3种氧化应激生物标志物8-OHdG、8-异前列腺素和TAC。分析了LUTD亚组与IC/BPS患者之间的尿液生物标志物水平。本研究结果显示，患者中48例诊断为IC/BPS，66例为BOO，25例为DO，27例为HSB，15例为PRES，17例正常。BOO患者的逼尿肌压力和BOO指数高于IC/BPS患者，而IC/BPS、BOO和DO患者的膀胱容量测量值小于PRES和正常亚组。在尿液生物标志物中，IC/BPS患者的嗜酸性粒细胞趋化因子、MCP-1、TNF-α、8-OHdG和TAC水平显著高于所有其他LUTD亚组。通过联合不同的特征性尿液生物标志物，TNF-α和嗜酸性粒细胞趋化因子单独或联合使用时，对鉴别IC/BPS与所有其他LUTD亚组、BOO、DO或HSB亚组患者具有最高的敏感性、特异性、阳性预测值和阴性预测值。炎症生物标志物MCP-1和氧化应激生物标志物8-OHdG及TAC，虽然在IC/BPS患者中显著高于正常和PRES亚组，但在IC/BPS男性患者与BOO、DO或HSB亚组之间没有诊断价值。该研究得出结论，单独或联合使用尿液TNF-α和嗜酸性粒细胞趋化因子水平，可作为生物标志物，用于鉴别LUTS男性患者中IC/BPS与其他LUTD亚组。
