Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.
Department of Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.
Int J Mol Sci. 2022 Oct 10;23(19):12044. doi: 10.3390/ijms231912044.
This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner's lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner's IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner's IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.
本研究旨在探讨尿生物标志物在评估间质性膀胱炎/膀胱疼痛综合征(IC/BPS)患者膀胱状况和组织病理学方面的作用。我们回顾性纳入了 315 名(267 名女性和 48 名男性)IC/BPS 患者和 30 名对照者。记录了临床和尿动力学特征(视觉模拟评分(VAS)和膀胱容量)和膀胱镜下注水扩张的发现(Hunner 病变、肾小球分级和最大膀胱容量(MBC))。利用尿液样本检测炎症、神经源性和氧化应激生物标志物,包括白细胞介素(IL)-8、C-X-C 基序趋化因子配体 10(CXCL10)、单核细胞趋化蛋白-1(MCP-1)、脑源性神经营养因子(BDNF)、嗜酸性粒细胞趋化因子、IL-6、巨噬细胞炎症蛋白 1β(MIP-1β)、调节激活正常 T 细胞表达和分泌(RANTES)、肿瘤坏死因子-α(TNF-α)、前列腺素 E2(PGE2)、8-羟基-2'-脱氧鸟苷(8-OHdG)和 8-异前列腺素,以及总抗氧化能力。此外,通过膀胱活检确定了特定的组织病理学发现。评估了尿生物标志物水平与膀胱状况和组织病理学发现之间的关系。结果表明,与对照组相比,IC/BPS 患者的尿 MCP-1、嗜酸性粒细胞趋化因子、TNF-α、PGE2、8-OHdG 和 8-异前列腺素水平明显更高。Hunner 间质性膀胱炎(HIC)患者的 IL-8、CXCL10、BDNF、嗜酸性粒细胞趋化因子、IL-6、MIP-1β 和 RANTES 水平明显高于非 Hunner 间质性膀胱炎(NHIC)患者。NHIC 患者 MBC≤760ml 时,尿 CXCL10、MCP-1、嗜酸性粒细胞趋化因子、IL-6、MIP-1β、RANTES、PGE2 和 8-异前列腺素及总抗氧化能力明显升高。NHIC 患者肾小球分级较高时,尿 MCP-1、IL-6、RANTES、8-OHdG 和 8-异前列腺素水平明显升高。尿生物标志物与肾小球分级、MBC、VAS 评分和膀胱感觉之间存在显著相关性。然而,膀胱特异性组织病理学发现与尿生物标志物水平相关性不佳。尿生物标志物水平可用于识别 HIC 和不同的 NHIC 亚型。较高的尿炎症和氧化应激生物标志物水平与 IC/BPS 相关。大多数尿生物标志物与特定的膀胱组织病理学发现不相关;然而,它们在评估膀胱状况方面比膀胱组织病理学更为重要。