利用尿液生物標誌來識別間質性膀胱炎/膀胱疼痛症女性病患的膀胱不同表現型

劉民慶、江元宏、李雨霜、楊家誠、黃子修、張天霖、陳聖復、張嘉峰、游婉茹、郭漢崇

花蓮慈濟醫院

Use of Cluster of Urinary Biomarkers for Identifying Interstitial Cystitis and Bladder Conditions in Women with Interstitial Cystitis/Bladder Pain Syndrome

Min-Ching Liu, Yuan-Hong Jiang, Yu-Shuang Lee, Chia-Cheng Yang, Tsu-Hsiu Huang, Tien-Lin Chang, Sheng-Fu Chen, Jia-Fong Jhang, WanRu Yu, Hann-Chorng Kuo

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition causing bladder inflammation, and bladder pain symptoms. Urinary biomarkers have been assessed suitable for the diagnosis and treatment guidance for lower urinary tract dysfunctions. This study investigated the diagnostic role of urinary biomarkers in identifying different phenotypes and bladder conditions in women with IC/BPS.

Materials and methods: A total of 376 patients with established diagnosis of IC/BPS, 16 bladder hypersensitivity, and 30 normal were enrolled in this study. All patients underwent a comprehensive urological workup and urine levels of 15 urinary biomarkers. Patients with IC/BPS were further classified into the Hunner’s IC (HIC) and non-HIC (NHIC) groups. The dataset was randomly allocating 70% to the training set and 30% to the test set to support both internal and external validation processes. The median level of urinary biomarkers in the cohort of controls and bladder hypersensitivity were used as the normal cut-off value. Logistic regression was employed to determine the most significant urinary biomarker for identifying IC subtypes or bladder conditions, and the cut-off value of the biomarkers.

Results: Among the training set with 265 IC/BPS and 32 control women, urinary biomarker TNF-α≥Q3, 8-OHdG ≥Q3, and 8-isoprostane≥Q2 were most significant biomarkers to identify IC/BPS from the cohort. The sensitivity and specificity using TNF-α ≥Q3 or 8-OHdG ≥Q3, and 8-isoprostane≥Q2 were 76.2% and 75.0% in training set, and 78.4% and 71.4% in test set, respectively. Among 376 women with IC/BPS, IP10 had the most significant AUC among urinary biomarkers, (0.803 ± 0.047) to identify HIC and NHIC. The sensitivity and specificity were 81.8% and 67.5% in the training set, and 70.0% and 67.0% in the test set, respectively. The IP10 level was also significantly higher in women with HIC than NHIC, both in the training and test set (Figure 1).

Conclusion: Using urinary biomarker TNF-α, 8-OHdG, and 8-isoprostane, women with TNF-α ≥Q3 or 8-OHdG ≥Q3, and 8-isoprostane≥Q2 had a high sensitivity to identify IC/BPS. Among patients with IC/BPS, IP10 can provide a diagnostic aid to identify HIC, and the higher urinary level of IP10 imply a higher grade of glomerulation and small MBC under cystoscopic hydrodistention.

Figure. The diagnosis of IC/BPS and differentiate subtypes and bladder condition by cluster of urinary biomarkers.