{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:41:58Z","timestamp":1782484918222,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCMF-MP-110-03-01"],"award-info":[{"award-number":["TCMF-MP-110-03-01"]}]},{"name":"Buddhist Tzu Chi Medical Foundation","award":["TCMF-SP-112-01"],"award-info":[{"award-number":["TCMF-SP-112-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Women commonly experience urinary tract infection (UTI) recurrence. However, there is no effective tool for predicting recurrent UTI after the first UTI episode. Hence, this study aimed to investigate potential urinary inflammatory biomarkers and specific biomarkers for predicting UTI recurrence or persistence after antibiotic treatment in women. Forty women who had a history of recurrent UTI within 1 year after the initial episode and acute bacterial cystitis were treated with broad-spectrum antibiotics for 1 week. To measure inflammatory biomarker levels, urine samples were collected at the baseline and after 1 week, 1 month, and 3 months. The levels of urinary pro-inflammatory proteins such as neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor, CXC-motif chemokine ligand (CXCL)-1, interleukin-8, CXCL-10, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha were measured using commercial kits. Seven healthy age-matched women were included as controls. The changes in urinary biomarker levels at the baseline and various time points were compared between women with and without UTI recurrence within 1 month or within 3 months after the initial antibiotic therapy. At the baseline, patients with a higher urinary white blood cell count had a significantly higher NGAL level than the controls and those with a low white blood cell count. Of the 40 patients with a history of recurrent UTI, 12 presented with UTI persistence or recurrence within 1 month and 19 within 3 months after the initial antibiotic treatment. Among the 28 patients without UTI recurrence at 1 month after treatment, 7 had UTI recurrence within 3 months. Compared with patients without UTI recurrence, those with UTI recurrence had significantly higher urinary NGAL levels at 1 week, 1 month, and 3 months after the initial treatment. This study concludes that persistent elevation in urinary NGAL levels after the initial antibiotic treatment indicated persistent bladder inflammation. Further, it could be a predictor of UTI persistence or recurrence within 1 or 3 months after the initial antibiotic treatment. Patients with a history of recurrent UTI and high urinary NGAL levels after antibiotic treatment might require a longer treatment duration to completely eradicate or prevent UTI recurrence.<\/jats:p>","DOI":"10.3390\/ijms252312670","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"12670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Persistent Elevation in Urinary Neutrophil Gelatinase-Associated Lipocalin Levels Can Be a Predictor of Urinary Tract Infection Recurrence or Persistence in Women"],"prefix":"10.3390","volume":"25","author":[{"given":"Min-Ching","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7870-1574","authenticated-orcid":false,"given":"Yuan-Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and 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, and Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Lin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and 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, and Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","unstructured":"European Association of Urology (2020). EAU Guidelines\u2013Urological Infections, EAU Annual Congress."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s15010-012-0347-1","article-title":"Risk factors for non-Escherichia coli community-acquired bacteriuria","volume":"41","author":"Amna","year":"2013","journal-title":"Infection"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"392","DOI":"10.3122\/15572625-13-6-392","article-title":"Quality of life in women with urinary tract infections: Is benign disease a misnomer?","volume":"13","author":"Ellis","year":"2000","journal-title":"J. Am. Board. Fam. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1067\/mda.2003.7","article-title":"Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs","volume":"49","author":"Foxman","year":"2003","journal-title":"Dis. Mon."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/clinids\/22.1.91","article-title":"Recurrence of urinary tract infection in a primary care setting: Analysis of a 1-year follow-up of 179 women","volume":"22","author":"Siitonen","year":"1996","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1007\/s00467-024-06321-9","article-title":"Biomarkers for urinary tract infection: Present and future perspectives","volume":"39","author":"Mattoo","year":"2024","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/bju.15630","article-title":"Management of uncomplicated recurrent urinary tract infections","volume":"129","author":"Zare","year":"2022","journal-title":"BJU Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chuang, F.C., and Kuo, H.C. (2013). Increased urothelial cell apoptosis and chronic inflammation are associated with recurrent urinary tract infection in women. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063760"},{"key":"ref_9","first-page":"131","article-title":"Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention","volume":"29","author":"Jhang","year":"2017","journal-title":"Ci Ji Yi Xue Za Zhi"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hayes, B.W., and Abraham, S.N. (2016). Innate Immune Responses to Bladder Infection. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.UTI-0024-2016"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e202302323","DOI":"10.26508\/lsa.202302323","article-title":"Inflammatory markers for improved recurrent UTI diagnosis in postmenopausal women","volume":"7","author":"Ebrahimzadeh","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00430-015-0394-1","article-title":"Neutrophil gelatinase-associated lipocalin and innate immune responses to bacterial infections","volume":"204","author":"Nasioudis","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chen, C., Mitsnefes, M., Huang, B., and Devarajan, P. (2024). Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: A meta-analysis. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1368583"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Leitner, L., Schneidewind, L., Bonkat, G., Stangl, F.P., and Kranz, J. (2024). Urodynamic Risk Factors for Urinary Infection. Eur. Urol. Focus., Online ahead of print.","DOI":"10.1016\/j.euf.2024.08.003"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e619","DOI":"10.3399\/BJGP.2024.0015","article-title":"Recurrent urinary tract infections and prophylactic antibiotic use in women: A cross-sectional study in primary care","volume":"74","author":"Sanyaolu","year":"2024","journal-title":"Br. J. Gen. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/luts.12351","article-title":"Deficits of urothelial cell proliferation, cytoskeleton, and barrier function protein expressions in patients with recurrent and persistent urinary tract infections","volume":"13","author":"Jhang","year":"2021","journal-title":"Low. Urin. Tract. Symptoms."},{"key":"ref_17","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. Renal Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jhang, J.F., Ho, H.C., Hsu, Y.H., Jiang, Y.H., and Kuo, H.C. (2022). Bladder Ultrastructure and Urinary Cytokine Abnormality in Patients with Recurrent Urinary Tract Infection and the Changes after Intravesical Platelet-Rich Plasma Injections. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020245"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.4049\/jimmunol.1401528","article-title":"Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection","volume":"193","author":"Steigedal","year":"2014","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Romejko, K., Markowska, M., and Niemczyk, S. (2023). The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310470"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1515\/CCLM.2011.156","article-title":"Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia","volume":"49","author":"Decavele","year":"2011","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1007\/s00467-020-04854-3","article-title":"Neutrophil gelatinase-associated lipocalin for urinary tract infection and pyelonephritis: A systematic review","volume":"36","author":"Shaikh","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1007\/s00467-020-04654-9","article-title":"Urine neutrophil gelatinase-associated lipocalin in girls with recurrent urinary tract infections","volume":"35","author":"Forster","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gavrilovici, C., Dusa, C.P., Iliescu Halitchi, C., Lupu, V.V., Spoiala, E.L., Bogos, R.A., Mocanu, A., Gafencu, M., Lupu, A., and Stoica, C. (2023). The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097904"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00431-018-3221-z","article-title":"Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: A systematic review and meta-analysis","volume":"177","author":"Bellos","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_26","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. Renal Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00327-18","DOI":"10.1128\/IAI.00327-18","article-title":"Urine Cytokine and Chemokine Levels Predict Urinary Tract Infection Severity Independent of Uropathogen, Urine Bacterial Burden, Host Genetics, and Host Age","volume":"86","author":"Armbruster","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/j.pain.0000000000001692","article-title":"Innate immune response to bacterial urinary tract infection sensitises high-threshold bladder afferents and recruits silent nociceptors","volume":"161","author":"Brierley","year":"2020","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhou, Z., Zheng, L., Gong, Z., Li, Y., Jin, Y., Huang, Y., and Chi, M. (2023). Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310537"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Acevedo-Monroy, S.E., Rocha-Ram\u00edrez, L.M., Mart\u00ednez G\u00f3mez, D., Basurto-Alc\u00e1ntara, F.J., Medina-Contreras, \u00d3., Hern\u00e1ndez-Chi\u00f1as, U., Qui\u00f1ones-Pe\u00f1a, M.A., Garc\u00eda-Sosa, D.I., Ram\u00edrez-Lezama, J., and Rodr\u00edguez-Garc\u00eda, J.A. (2024). Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116157"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eadi5578","DOI":"10.1126\/sciimmunol.adi5578","article-title":"Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity","volume":"9","author":"Hayes","year":"2024","journal-title":"Sci. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s11255-009-9647-5","article-title":"Urine cytokines suggest an inflammatory response in the overactive bladder: A pilot study","volume":"42","author":"Tyagi","year":"2010","journal-title":"Int. Urol. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:39:23Z","timestamp":1760114363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":32,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312670"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312670","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,26]]}}}