{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:03:31Z","timestamp":1791241411925,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCMF-SP-112-01"],"award-info":[{"award-number":["TCMF-SP-112-01"]}]},{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCMF-MP-110-03-01"],"award-info":[{"award-number":["TCMF-MP-110-03-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: lower urinary tract dysfunctions (LUTDs) are difficult to diagnose based on symptoms. This study used a cluster of urinary biomarkers, including inflammatory cytokines, neurogenic proteins, and oxidative stress biomarkers, to identify LUTDs in women with frequency and urgency symptoms. Methods: in total, 253 women with video urodynamics (VUDS)- and cystoscopy-confirmed detrusor overactivity (DO), interstitial cystitis\/bladder pain syndrome (IC\/BPS), dysfunctional voiding (DV), and hypersensitive bladder (HSB), and normal controls were included. Before diagnosis and treatment, urine samples were collected for analysis of biomarkers. The urine levels of biomarkers were compared between groups with bladder dysfunctions and controls and were combined to test the sensitivity in identifying total pathological bladder diseases and specific bladder diseases. Results: After video urodynamic study, VUDS, and urological examinations, bladder dysfunctions were classified into DO (n = 31), IC\/BPS (n = 114), DV (n = 45), HSB (n = 29), and control (n = 34) groups. By using a cystomeric bladder capacity of \u2264350 mL, 186\/219 (84.9%) of the patients with DO, IC\/BPS, DV, and HSB can be discriminated from the controls. Among these urine biomarkers, oxidative stress biomarkers 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), or total antioxidant capacity (TAC) are useful for identifying pathological bladder dysfunction (DO, IC\/BPS, and DV) and HSB. With elevated IL-1\u03b2 and lower IL-2, and elevated TNF-\u03b1 levels, most patients with DV can be identified. Between DO and IC\/BPS, a higher NGF level can identify 58.3% of IC\/BPS cases, whereas a lower NGF level can identify 75.0% of DO cases. Conclusion: by using a cluster of urine biomarkers, DO, IC\/BPS, and DV cases can be identified based on elevated levels of urine oxidative stress biomarkers 8-isoprostane, TAC, or 8-OHdG, and HSB cases with a low TAC. These urine biomarkers are useful for identifying specific LUTDs in women with frequency and urgency symptoms.<\/jats:p>","DOI":"10.3390\/jcm12062336","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T02:29:59Z","timestamp":1679020199000},"page":"2336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Urinary Oxidative Stress Biomarker Levels Might Be Useful in Identifying Functional Bladder Disorders in Women with Frequency and Urgency Syndrome"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-1574","authenticated-orcid":false,"given":"Yuan-Hong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Fong","family":"Jhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-4771","authenticated-orcid":false,"given":"Hann-Chorng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1757-5672.2012.00160.x","article-title":"Lower urinary tract symptoms and video-urodynamic characteristics of women with clinically unsuspected bladder outlet obstruction","volume":"5","author":"Chuang","year":"2013","journal-title":"Low Urin. Tract Symptoms"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jfma.2011.05.014","article-title":"Clinical symptoms are not reliable in the diagnosis of lower urinary tract dysfunction in women","volume":"111","author":"Kuo","year":"2012","journal-title":"J. Formos Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00192-022-05154-0","article-title":"Effect of videourodynamic subtypes on treatment outcomes of female dysfunctional voiding","volume":"33","author":"Lee","year":"2022","journal-title":"Int. Urogynecol. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.euf.2019.06.006","article-title":"Urinary biomarkers in overactive bladder: Revisiting the evidence in 2019","volume":"5","author":"Cruz","year":"2019","journal-title":"Eur. Urol. Focus"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lin, H.Y., Lu, J.H., Chuang, S.M., Chueh, K.S., Juan, T.J., Liu, Y.C., and Juan, Y.S. (2021). Urinary biomarkers in interstitial cystitis\/bladder pain syndrome and its impact on therapeutic outcome. Diagnostics, 12.","DOI":"10.3390\/diagnostics12010075"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1097\/JU.0000000000001031","article-title":"Hunner lesion phenotype in interstitial cystitis\/bladder pain syndrome: A systematic review and meta-analysis","volume":"204","author":"Lai","year":"2020","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4081\/aiua.2022.3.355","article-title":"Systematic review of urinary biomarkers of female bladder outlet obstruction (fBOO)","volume":"94","author":"Dinis","year":"2022","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1007\/s11255-022-03265-7","article-title":"Performance of urinary biomarkers in differentiating dysfunctional voiding in women with overactive bladder syndrome: A prospective pilot study","volume":"54","author":"Chow","year":"2022","journal-title":"Int. Urol. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/JU.0000000000000257","article-title":"Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN). Biomarkers implicated in lower urinary tract symptoms: Systematic review and pathway analyses","volume":"202","author":"Siddiqui","year":"2019","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/nau.10052","article-title":"Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-Committee of the International Continence Society","volume":"21","author":"Abrams","year":"2002","journal-title":"Neurourol. Urodyn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","article-title":"Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: An ESSIC proposal","volume":"53","author":"Nordling","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/s41598-020-80131-5","article-title":"Urine biomarkers in ESSIC type 2 interstitial cystitis\/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm","volume":"11","author":"Jiang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"F1391","DOI":"10.1152\/ajprenal.00051.2020","article-title":"Urine cytokines as biomarkers for diagnosing interstitial cystitis\/bladder pain syndrome and mapping its clinical characteristics","volume":"318","author":"Jiang","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Jhang, J.F., Ho, H.C., Chiou, D.Y., and Kuo, H.C. (2022). Urine oxidative stress biomarkers as novel biomarkers in interstitial cystitis\/bladder pain syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071701"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4103\/tcmj.tcmj_264_20","article-title":"Effects of different urodynamic characteristics on therapeutic outcomes of overactive bladder medication in a real-life clinical practice","volume":"34","author":"Wang","year":"2022","journal-title":"Tzu Chi Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/JU.0000000000002756","article-title":"Diagnosis and treatment of interstitial cystitis\/bladder pain syndrome","volume":"208","author":"Clemens","year":"2022","journal-title":"J. Urol."},{"key":"ref_17","first-page":"25","article-title":"Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases","volume":"57","year":"2004","journal-title":"Arch. Esp. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1002\/nau.23263","article-title":"Videourodynamic analysis of the urethral sphincter overactivity and the poor relaxing pelvic floor muscles in women with voiding dysfunction","volume":"36","author":"Peng","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/luts.12395","article-title":"Chronic psychological stress and lower urinary tract symptoms","volume":"13","author":"McDermott","year":"2021","journal-title":"Low Urin. Tract Symptoms"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"F548","DOI":"10.1152\/ajprenal.00213.2016","article-title":"Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI","volume":"311","author":"Tyagi","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1038\/s41598-022-10696-w","article-title":"Diagnostic and prognostic value of urine biomarkers among women with dysfunctional voiding","volume":"12","author":"Jiang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.urology.2021.05.005","article-title":"Diagnostic utility of serum and urinary metabolite analysis in patients with interstitial cystitis\/painful bladder syndrome","volume":"157","author":"Kim","year":"2021","journal-title":"Urology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1002\/nau.24313","article-title":"Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019","volume":"39","author":"Speich","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/nau.21191","article-title":"Increased bladder activity is associated with elevated oxidative stress markers and proinflammatory cytokines in a rat model of atherosclerosis-induced chronic bladder ischemia","volume":"31","author":"Nomiya","year":"2012","journal-title":"Neurourol. Urodyn."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, Y.H., Chueh, K.S., Chuang, S.M., Long, C.Y., Lu, J.H., and Juan, Y.S. (2021). Bladder hyperactivity induced by oxidative stress and bladder ischemia: A review of treatment strategies with antioxidants. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116014"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4111\/icu.2018.59.4.252","article-title":"Measuring urinary 8-hydroxy-2\u2032-deoxyguanosine and malondialdehyde levels in women with overactive bladder","volume":"59","author":"Dokumacioglu","year":"2018","journal-title":"Investig. Clin. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/S0022-5347(17)36253-5","article-title":"Impaired bladder perfusion in interstitial cystitis: A study of blood supply using laser Doppler flowmetry","volume":"149","author":"Irwin","year":"1993","journal-title":"J. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S0022-5347(05)68552-7","article-title":"Comparison of bladder blood flow in patients with and without interstitial cystitis","volume":"162","author":"Pontari","year":"1999","journal-title":"J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"971.e11","DOI":"10.1016\/j.urology.2011.05.050","article-title":"Increased expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor associated with glomerulation formation in patients with interstitial cystitis","volume":"78","author":"Lee","year":"2011","journal-title":"Urology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/j.1464-410X.2009.08467.x","article-title":"Increased vascular endothelial growth factor expression in patients with bladder pain syndrome\/interstitial cystitis: Its association with pain severity and glomerulations","volume":"104","author":"Kiuchi","year":"2009","journal-title":"BJU Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1007\/s00192-021-04945-1","article-title":"The use of urinary biomarkers in the diagnosis of overactive bladder in female patients. A systematic review and meta-analysis","volume":"32","author":"Tsiapakidou","year":"2021","journal-title":"Int. Urogynecol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrurol.2012.178","article-title":"Neurotrophins as regulators of urinary bladder function","volume":"9","author":"Ochodnicky","year":"2012","journal-title":"Nat. Rev. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.4111\/icu.2020.61.S1.S8","article-title":"Advances in urinary biomarker discovery in urological research","volume":"61","author":"Kim","year":"2020","journal-title":"Investig. Clin. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s00192-017-3547-5","article-title":"Comparison of inflammatory urine markers in patients with interstitial cystitis and overactive bladder","volume":"29","author":"Furuta","year":"2018","journal-title":"Int. Urogynecol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1038\/s41598-021-87040-1","article-title":"Improves symptoms and urinary biomarkers in refractory interstitial cystitis\/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo","volume":"11","author":"Shen","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Miyazaki, N., Katsura, R., Hamada, K., and Suzutani, T. (2020). Blueberry prevents the bladder dysfunction in bladder outlet obstruction rats by attenuating oxidative stress and suppressing bladder remodeling. Nutrients, 12.","DOI":"10.3390\/nu12051285"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1249.e1","DOI":"10.1016\/j.urology.2014.07.023","article-title":"Effects of ischemia and oxidative stress on bladder purinoceptors expression","volume":"84","author":"Zhang","year":"2014","journal-title":"Urology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1002\/nau.24487","article-title":"The profile of urinary biomarkers in overactive bladder","volume":"39","author":"Rada","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/CIRCRESAHA.117.311401","article-title":"Reactive oxygen species in metabolic and inflammatory signaling","volume":"122","author":"Forrester","year":"2018","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1161\/CIRCRESAHA.116.303584","article-title":"Regulation of signal transduction by reactive oxygen species in the cardiovascular system","volume":"116","author":"Brown","year":"2015","journal-title":"Circ. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/6\/2336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:14Z","timestamp":1760122634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/6\/2336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jcm12062336"],"URL":"https:\/\/doi.org\/10.3390\/jcm12062336","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742589057.793598280","asserted-by":"object"}]},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}