POL Scientific / Bladder / Volume 2 / Issue 1 / DOI: 10.14440/bladder.2015.36
Cite this article
22
Citations
67
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
RESEARCH ARTICLE

Data do not support the use of elevated urinary nerve growth factor and fractalkine levels as diagnostic and prognostic biomarkers for women with overactive bladder

Erem Kaan Basok1* Banu Isbilen Basok2 Eyup Sabri Pelit3 Asif Yildirim3 Ferruh Kemal Isman2 Turhan Caskurlu3
Show Less
1 Department of Urology, Bahcesehir University, School of Medicine, Istanbul, Turkey
2 Department of Biochemistry, S.B. Istanbul Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
3 Department of Urology, S.B. Istanbul Medeniyet University, Goztepe Education and Research Hospital, Istanbul, Turkey
Bladder 2015 , 2(1), 1–7;
Published: 15 January 2015
© 2015 by the Author(s). Licensee POL Scientific, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Objective: This study investigated urinary nerve growth factor (NGF) and fractalkine levels in women with overactive bladder (OAB), as well as diagnostic and/or prognostic roles, and correlation of these urinary biomarkers with symptom severity of patients.

Materials and Methods: Twenty-seven women with OAB and 26 healthy subjects were enrolled. Patients were diagnosed with OAB based on symptoms, a 3-day voiding diary and a validated Turkish version of the Overactive Bladder-Validated 8 (OAB-V8) questionnaire. The urinary baseline levels of NGF and fractalkine were compared between OAB patients and control group. The Turkish-validated International Consultation on Incontinence Questionnaire Short Form and OAB-V8 used to categorize patients according to disease severity to assess treatment efficacy. Further urinary NGF and fractalkine levels were compared before and after antimuscarinic treatment.

Results: Urinary NGF/creatinine (Cr) and fractalkine/Cr were significantly elevated in OAB patients (0.40 ± 0.40 ng/mg and 4.63 ± 4.36 ng/mg, respectively) compared to healthy subjects (0.14 ± 0.08 ng/mg and 2.00 ± 1.29 ng/mg, P = 0.002 and P = 0.005, respectively). Sensitivity and specificity were 85.2%, 65.4% for NGF, and 74.1%, 65.4% for fractalkine, respectively. No significant differences in NGF/Cr and fractalkine/Cr compared to baseline (P = 0.063 and 0.162, respectively) were observed after trospium chloride treatment in OAB patients. NGF/Cr and fractalkine/Cr exhibited no correlations with symptom severity levels.

Conclusions: Increased urinary NGF/Cr and fractalkine/Cr levels were found in OAB women. However, the sensitivity and specificity were not sufficient for diagnostic use. NGF and fractalkine levels were decreased after treatment insignificantly, and there was no correlation with symptom severity; therefore their prognostic worth was limited.

Keywords
chemokine
fractalkine
nerve growth factor
overactive bladder
urinary biomarker
References

1. Hashim H, Abrams P (2006). Is the bladder a reliable witness for predicting detrusor overactivity? J Urol. 175: 191-5.
2. Antunes-Lopes T, Carvalho-Barros S, Cruz CD, et al (2011). Biomarkers in overactive bladder: a new objective and noninvasive tool? Adv Urol. 382431doi: 10.1155/2011/382431.
3. Tyagi P, Barclay D, Zamora R, et al (2010). Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol. 42: 629-35.
4. Bouchelouche K, Alvarez S, Horn T, et al (2006). Human detrusor smooth muscle cells release interleukin-6, interleukin-8, and RANTES in response to proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha. Urology 67: 214–9
5. Compérat E, Reitz A, Delcourt A, et al (2006). Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A. Eur Urol. 50: 1058-64.
6. Apostolidis A, Jacques TS, Freeman A, et al (2008). Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity. Eur Urol. 53: 1245-53
7. D'Haese JG, Demir IE, Friess H, et al (2010). Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential. Expert Opin Ther Targets. 14: 207-19. Review
8. Yuridullah R, Corrow KA, Malley SE, et al (2006). Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis. Auton Neurosci. 126-127: 380-9.
9. Cheung WW, Borawski D, Abulafia O, et al (2011). Characterization of overactive bladder in women in a primary care setting. Open Access Journal of Urology. 3: 29-34.
10. Cetinel B, Demirkesen O, Tarcan T, et al (2007). Hidden female urinary incontinence in urology and obstetrics and gynecology outpatient clinics in Turkey: what are the determinants of bothersome urinary incontinence and help-seeking behavior? Int Urogynecol J Pelvic Floor Dysfunct. 18: 659-64.
11. Cartwright R, Afshan I, Derpapas A, et al (2011). Novel biomarkers for overactive bladder. Nat Rev Urol. 8: 139-45.
12. Chung SD, Chiu B, Kuo HC, et al (2010). Transabdominal ultrasonography of detrusor wall thickness in women with overactive bladder. BJU Int. 105: 668-72.
13. Chung SD, Liu HT, Lin H, et al (2011). Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder. Neurourol Urodyn. 30: 417-20.
14. Kupelian V, McVary KT, Barry MJ, et al (2009). Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston Area Community Health survey. Urology. 73: 950-7.
15. Cho KJ, Kim HS, Koh JS, et al (2013). Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics. Int Urogynecol J. 24: 325-30.
16. Frias B, Allen S, Dawbarn D, et al (2013). Brain Derived Neurotrophic Factor (BDNF), acting at the spinal cord level, participates in bladder hyperactivity and referred pain during chronic bladder inflammation. Neuroscience. 234: 88-102.
17. Liu HT, Chen CY, Kuo HC (2011). Urinary nerve growth factor in women with overactive bladder syndrome. BJU Int. 107: 799-803.
18. Liu HT, Chen CY, Kuo HC (2010). Urinary nerve growth factor levels in overactive bladder syndrome and lower urinary tract disorders. J Formos Med Assoc. 109: 862-78. Review
19. Antunes-Lopes T, Pinto R, Barros SC, et al (2013). Urinary neurotrophic factors in healthy individuals and patients with overactive bladder. J Urol. 189: 359-65.
20. Birder LA, Wolf-Johnston A, Griffiths D, et al (2007). Role of urothelial nerve growth factor in human bladder function. Neurourol Urodyn. 26: 405-9.
21. Seth JH, Sahai A, Khan MS, et al (2013). Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)? BJU Int. 111: 372-80. Review.
22. Liu HT, Chancellor MB, Kuo HC (2009). Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol. 56: 700-6.
23. Kuo HC, Liu HT, Chancellor MB (2010). Can urinary nerve growth factor be a biomarker for overactive bladder? Rev Urol. 12: 69-77.
24. Rachaneni S, Arya P, Latthe P (2013). Urinary nerve growth factor: a biomarker of detrusor overactivity? A systematic review. Int Urogynecol J. 24: 1603-9.
25. Liu HT, Lin H, Kuo HC (2011). Increased serum nerve growth factor levels in patients with overactive bladder syndrome refractory to antimuscarinic therapy. Neurourol Urodyn. 30: 1525-9.
26. Tyagi P, Killinger K, Tyagi V, et al (2012). Urinary chemokines as noninvasive predictors of ulcerative interstitial cystitis. J Urol. 187: 2243-8.
27. Ghoniem G, Faruqui N, Elmissiry M, et al (2011). Differential profile analysis of urinary cytokines in patients with overactive bladder. Int Urogynecol J. 22: 953-61.
28. Ruhin Yuridullah, Kimberly A. Corrow, Susan E. Malley, et al (2006). Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis. Auton Neurosci. 126-127: 380–389.

Share
Back to top
Bladder, Electronic ISSN: 2327-2120 Print ISSN: TBA, Published by POL Scientific