Skip to main content

Advertisement

SpringerLink
Log in

Urinary brain-derived neurotrophic factor: a potential biomarker for objective diagnosis of overactive bladder

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the diagnostic performance of urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) as potential biomarkers for overactive bladder (OAB).

Methods

Ninety women diagnosed with OAB and 45 normal controls without OAB were enrolled. Urine samples were collected from all subjects. Urinary BDNF and NGF levels were measured using enzyme-linked immunosorbent assays. Results normalized by urinary creatinine (Cr) levels were compared between OAB groups and controls. Symptom severity was assessed using overactive bladder symptom score.

Results

Urinary BDNF and NGF levels were elevated in OAB groups but not in controls. Mean (SD) baseline BDNF and NGF levels normalized by Cr levels were significantly higher in OAB subjects than in controls (20.609 ± 23.932 vs. 1.779 ± 0.729, p < 0.01) and (0.258 ± 0.264 vs. 0.081 ± 0.028, p < 0.01), respectively. Urinary BDNF/Cr levels were 80-fold higher than NGF/Cr levels in OAB subjects. Receiver operating characteristic curves for assessing urinary BDNF/Cr levels in OAB groups showed sensitivity and specificity of 93.33 and 88.89 %, respectively. Urinary BDNF levels were associated with OAB symptom severity.

Conclusions

Urinary BDNF/Cr levels are elevated in women with OAB and are significantly associated with symptom severity. No elevation of BDNF is found in women without OAB. BDNF analysis has better sensitivity than NGF in detecting OAB in subjects without other lower urinary tract disorders. Results of the present study suggest a potential role for BDNF as an objective biomarker for OAB diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Milsom I, Kaplan SA, Coyne KS et al (2012) Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: results from EpiLUTS. Urology 80:90

    Article  PubMed  Google Scholar 

  2. Stewart WF, Van Rooyen JB, Cundiff GW et al (2003) Prevalence and burden of overactive bladder in the United States. World J Urol 20:327

    CAS  PubMed  Google Scholar 

  3. Abrams P, Cardozo L, Fall M et al (2002) The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 21:167

    Article  PubMed  Google Scholar 

  4. NIDDK (2013) Urodynamic testing. National institute of diabetes and digestive and kidney diseases. http://kidney.niddk.nih.gov/kudiseases/pubs/bcw_ez. Accessed 16 May

  5. Rovner ES, Goudelocke CM (2010) Urodynamics in the evaluation of overactive bladder. Curr Urol Rep 11:343

    Article  PubMed  Google Scholar 

  6. Steers WD, Tuttle JB (2006) Mechanisms of disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol 3:101

    Article  CAS  PubMed  Google Scholar 

  7. Ochodnicky P, Cruz CD, Yoshimura N et al (2011) Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target. Neurourol Urodyn 30:1227

    CAS  PubMed  Google Scholar 

  8. Kuo HC, Liu HT, Chancellor MB (2010) Can urinary nerve growth factor be a biomarker for overactive bladder? Rev Urol 12:e69

    PubMed Central  PubMed  Google Scholar 

  9. Liu HT, Kuo HC (2008) Urinary nerve growth factor level could be a potential biomarker for diagnosis of overactive bladder. J Urol 179:2270

    Article  PubMed  Google Scholar 

  10. Antunes-Lopes T, Carvalho-Barros S, Cruz CD et al (2011) Biomarkers in overactive bladder: a new objective and noninvasive tool? Adv Urol 2011, Article ID 382431

  11. Antunes-Lopes T, Pinto R, Carvalho-Barros S et al (2011) Urinary levels of brain-derived neurotrophic factor (BDNF) in women with overactive bladder (OAB) syndrome correlate with the severity of symptoms. Eur Urol Suppl 10:277

    Article  Google Scholar 

  12. Kuo HC, Liu HT, Chancellor MB (2010) Urinary nerve growth factor is a better biomarker than detrusor wall thickness for the assessment of overactive bladder with incontinence. Neurourol Urodyn 29:482

    PubMed  Google Scholar 

  13. Kim JC, Park EY, Seo SI et al (2006) Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 175: 1773; discussion 1776

    Google Scholar 

  14. Kim JC, Park EY, Hong SH et al (2005) Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol 12:875

    Article  CAS  PubMed  Google Scholar 

  15. Liu HT, Tyagi P, Chancellor MB et al (2010) Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity. BJU Int 106:1681

    Article  PubMed  Google Scholar 

  16. Ghoniem G, Faruqui N, Elmissary M et al (2011) Differential profile analysis of urinary cytokines in patients with overactive bladder. Int Urogynecol J 22:953

    Article  PubMed  Google Scholar 

  17. Bhide AA, Cartwright R, Khullar V et al (2013) Biomarkers in overactive bladder. Int Urogynecol J 12 Jan (Epub ahead of print.)

  18. Homma Y, Yoshida M, Seki N et al (2006) Symptom assessment tool for overactive bladder syndrome–overactive bladder symptom score. Urology 68:318

    Article  PubMed  Google Scholar 

  19. Liu HT, Tyagi P, Chancellor MB et al (2009) Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int 104:1476

    Article  CAS  PubMed  Google Scholar 

  20. Florkowski CM (2008) Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests. Lin Biochem Rev 29(Suppl 1):S83

    Google Scholar 

  21. Mandrekar JN (2010) Receiver operating characteristics curve in diagnostic test assessment. J Thorac Oncol 5:1315

    Article  PubMed  Google Scholar 

  22. Liu HT, Kuo HC (2008) Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology 72: 104; discussion 108

    Google Scholar 

  23. 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

    Article  CAS  PubMed  Google Scholar 

  24. Obata K, Noguchi K (2006) BDNF in sensory neurons and chronic pain. Neurosci Res 55:1

    Article  CAS  PubMed  Google Scholar 

  25. Oddiah D, Anand P, McMahon SB et al (1998) Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. NeuroReport 9:1455

    Article  CAS  PubMed  Google Scholar 

  26. Di Luca M, Gardoni F, Finardi A et al (2001) NMDA receptor subunits are phosphorylated by activation of neurotrophin receptors in PSD of rat spinal cord. NeuroReport 12:1301

    Article  PubMed  Google Scholar 

  27. Cruz Duarte P, St-Jacques B, Ma W (2012) Prostaglandin E2 contributes to the synthesis of brain-derived neurotrophic factor in primary sensory neurons in ganglion explant cultures and in a neuropathic pain model. Exp Neurol 234:466

    Article  CAS  PubMed  Google Scholar 

  28. Pezet S, McMahon SB (2006) Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 29:507

    Article  CAS  PubMed  Google Scholar 

  29. Qiao LY, Vizzard MA (2002) Cystitis-induced upregulation of tyrosine kinase (TrkA, TrkB) receptor expression and phosphorylation in rat micturition pathways. J Comp Neurol 454:200

    Article  CAS  PubMed  Google Scholar 

  30. Qiao LY, Vizzard MA (2005) Spinal cord injury-induced expression of TrkA, TrkB, phosphorylated CREB, and c-Jun in rat lumbosacral dorsal root ganglia. J Comp Neurol 482:142

    Article  CAS  PubMed  Google Scholar 

  31. Pinto R, Frias B, Allen S, Dawbarn D et al (2010) Sequestration of brain derived nerve factor by intravenous delivery of TrkB-Ig2 reduces bladder overactivity and noxious input in animals with chronic cystitis. Neuroscience 166:907

    Article  CAS  PubMed  Google Scholar 

  32. Pinto R, Lopes T, Frias B et al (2010) Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis. Eur Urol 58:360

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, The Second Affiliated Hospital to Nanchang University, Nanchang, 330006, People’s Republic of China

    Long-wang Wang

  2. Department of Urology, Union Hospital, Tongji Medical College, Huazhong Unicersity of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China

    Xiao-min Han, Chao-hui Chen, Yan Ma & Bo Hai

Authors
  1. Long-wang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-min Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao-hui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Hai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bo Hai.

Additional information

Long-wang Wang and Xiao-min Han contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Lw., Han, Xm., Chen, Ch. et al. Urinary brain-derived neurotrophic factor: a potential biomarker for objective diagnosis of overactive bladder. Int Urol Nephrol 46, 341–347 (2014). https://doi.org/10.1007/s11255-013-0540-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-013-0540-x

Keywords

Search

Navigation