尿液生物標記與皮膚交感神經活動提高急迫性尿失禁診斷準確性之初步研究

吳奕儒¹、陳浩瑋²、吳文正¹、阮雍順¹、陳妤甄¹

¹高雄醫學大學附設中和紀念醫院 泌尿科

²高雄市立大同醫院 泌尿科

A Pilot Study for Combination of Urine Biomarkers and Skin Sympathetic Nerve Activity in Improving Diagnostic Accuracy for Urge Urinary Incontinence

Yi-Ru Wu¹、Hao-Wei Chen²、Wen-Jeng WU¹、Yung-Shun Juan¹、Yu-Chen Chen^1
1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

²Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

ABSTRACT

Hypothesis / aims of study: The need for identification and development of overactive bladder (OAB) and urge urinary incontinence (UUI)-specific biomarkers was highlighted. Although few urine biomarkers have been proposed as diagnostic tools in patients with OAB and UUI, the main limitation of these studies is a lack of sensitivity and specificity. We recently reported that the significantly elevated skin sympathetic nerve activity (SKNA) was found in patients with OAB compared to controls, and that SKNA could be used as the potential diagnostic biomarker for OAB [1]. In this pilot study, we try to utilize SKNA combined with urine biomarkers to develop the novel diagnostic algorithm for UUI.

Study design, materials and methods: The prospective sample included 25 female participants: 10 patients newly diagnosed with UUI and 15 age-matched controls (non-UUI). Autonomic function was assessed in all participants in the morning using the noninvasive method “neuECG”, which analyzed the average SKNA in the baseline, stress and recovery phase. A representative 17 inflammatory growth factors, oxidatives, cytokines, chemokines, adipokines and autonomic catecholamines in urine were measured using the commercially available MILLIPLEX immunoassay kit and enzyme-linked immunosorbent assays, respectively. All urine biomarkers were corrected by urinary creatinine (Cre) and presented as urine biomarker-to-creatinine ratio (UBCR). The diagnostic efficiency of these markers was measured using receiver operating characteristic analysis.

Results: Significantly increased UBCR, including interukin-10 (IL-10), IL-15, CCL2, CXCL10 and vanillylmandelic acid (VMA), stress SKNA and recovery SKNA were found in UUI than those in controls (Table 1). Area under the curves for UBCR of IL-10, IL-15, CCL2, CXCL10 and VMA and stress SKNA and recovery SKNA to detect UUI were 0.843, 0.753, 0.693, 0.720, 0.753, 0.813 and 0.713 respectively (Table 2). A combination of IL-10 and CCL2 plus recovery SKNA (Model 4) achieved the highest value in diagnosing UUI (AUROC=0.967, p<0.001, sensitivity=90% and specificity=100%).

Interpretation of results: Patients with UUI seem to have more severe chronic bladder inflammation and sympathetic hyperactivity, as demonstrated by significant increases in UBCR of IL-10, IL-15, CCL2, CXCL10 and VMA and stress SKNA and recovery SKNA. The diagnostic model using the combination of IL-10/Cre, CCL2/Cre and recovery SKNA was shown to have the best diagnostic accuracy for UUI.

Conclusion: The increases in inflammatory cytokines and chemokines, such as IL-10 and CCL2, and sympathetic hyperactivity may be pathophysiologically important for the development of UUI. The study provides the foundation for the development of novel non-invasive and objective diagnostic tool for identifying UUI with the combination of urinary biomarkers and SKNA, which could improve the diagnostic accuracy for UUI.

Keywords: Overactive Bladder, Urgency Urinary Incontinence, Urgency/Frequency