Skip to main content

Advertisement

SpringerLink
Log in

Urinary biomarkers profiles in patients with neurogenic detrusor overactivity according to their neurological condition

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Objectives

The aim of this study was to investigate the disease-specific urinary levels variations of neurotrophins (NGF, BDNF), mediators of inflammation (TGFβ-1, PGE-2) and markers of extracellular matrix alterations (TIMP-2) in patients with multiple sclerosis (MS) spinal cord injury (SCI), or spina bifida (SB), and neurogenic detrusor overactivity (NDO).

Methods

A prospective single-center study was conducted between March 2015 and March 2017. Patients aged over 18 years old, with neurological disease, with a urodynamic diagnosis of NDO were included. The urinary levels of NGF, BDNF, TIMP-2, PGE 2, and TGF-β1 were measured using dedicated ELISA kits.

Results

Forty-one patients were included: 6 with MS, 20 with SCI, and 15 with spina bifida. The average urinary level of NGF/Cr was significantly higher in MS patients compared to other neurologic populations (8 vs. 0.56 vs. 1.25 pg/mg of creatinine; p = 0.001) as well for the average urinary level of BDNF (88.3 vs. 5 vs. 4.8 pg/mg of creatinine; p < 0.0001). SCI patients had a significantly lower level of TGFβ-1 than SB patients (p = 0.04). The urinary level of PGE2 was significantly correlated with the Body Mass Index (r = 0.61; p = 0.0002).

Conclusion

All NDO may not be created equal from the molecular standpoint. Multiple sclerosis patients had higher urinary levels of neurotrophins than in other neurologic populations with NDO. Urinary TGFβ-1, a strong determinant of extracellular matrix, was significantly higher in spina bifida patients compared to SCI patients. These findings underscore the importance of using and interpreting those possible urinary markers in a disease-specific fashion.

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. Gajewski JB, Schurch B, Hamid R, Averbeck M, Sakakibara R, Agrò EF et al (2018) An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD). Neurourol Urodyn 37(3):1152–1161

    Article  PubMed  Google Scholar 

  2. Haab F (2014) Chapter 1: the conditions of neurogenic detrusor overactivity and overactive bladder. Neurourol Urodyn 33(Suppl 3):S2–S5

    Article  PubMed  Google Scholar 

  3. Ruffion A, de Sèze M, Denys P, Perrouin-Verbe B, Chartier-Kastler E, Groupe d’Etudes de Neuro-Urologie de Langue Française (2007) Groupe d’Etudes de Neuro-Urologie de Langue Française (GENULF) guidelines for the management of spinal cord injury and spina bifida patients. Progres En Urol J Assoc Francaise Urol Soc Francaise Urol 17(3):631–633

    Article  CAS  Google Scholar 

  4. Decramer S, Gonzalez de Peredo A, Breuil B, Mischak H, Monsarrat B, Bascands J-L et al (2008) Urine in clinical proteomics. Mol Cell Proteom 7(10):1850–1862

    Article  CAS  Google Scholar 

  5. Peyronnet B, Bendavid C, Manunta A, Damphousse M, Cheensse C, Brochard C et al (2015) The role of urinary markers in the assessment and follow-up of lower urinary tract disorders: a literature review. Progres En Urol J Assoc Francaise Urol Soc Francaise Urol 25(4):188–199

    Article  CAS  Google Scholar 

  6. Top T, Sekerci CA, Isbilen-Basok B, Tanidir Y, Tinay I, Isman FK et al (2017) The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia. Neurourol Urodyn 36(7):1896–1902

    Article  CAS  PubMed  Google Scholar 

  7. Liu H-T, Chancellor MB, Kuo H-C (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(4):700–706

    Article  CAS  PubMed  Google Scholar 

  8. Yamauchi H, Akino H, Ito H, Aoki Y, Nomura T, Yokoyama O (2010) Urinary prostaglandin E2 was increased in patients with suprapontine brain diseases, and associated with overactive bladder syndrome. Urology 76(5):1267.e13–1267.e19

    Article  Google Scholar 

  9. Owens T (2003) The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage. Curr Opin Neurol 16(3):259–265

    Article  PubMed  Google Scholar 

  10. Neuhaus O, Archelos JJ, Hartung H-P (2003) Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. Trends Pharmacol Sci 24(3):131–138

    Article  CAS  PubMed  Google Scholar 

  11. Caggiula M, Batocchi AP, Frisullo G, Angelucci F, Patanella AK, Sancricca C et al (2005) Neurotrophic factors and clinical recovery in relapsing-remitting multiple sclerosis. Scand J Immunol 62(2):176–182

    Article  CAS  PubMed  Google Scholar 

  12. Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H (2006) The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. Neurol Sci 27(Suppl 1):S1–S7

    Article  PubMed  Google Scholar 

  13. Kalinowska-Lyszczarz A, Losy J (2012) The role of neurotrophins in multiple sclerosis—pathological and clinical implications. Int J Mol Sci 13(12):13713–13725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kerschensteiner M, Stadelmann C, Dechant G, Wekerle H, Hohlfeld R (2003) Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol 53(3):292–304

    Article  CAS  PubMed  Google Scholar 

  15. Bazhenov IV, Filippova ES, Bazarnyi VV, Sazonov SV, Volkova LI, Zaitseva LN (2019) Sensitivity and specificity of urinary and serum neurotrophins in the diagnosis of neurogenic detrusor overactivity in multiple sclerosis. Urol Mosc Russ 1999 3:44–48

    Google Scholar 

  16. Şekerci ÇA, Işbilen B, Işman F, Akbal C, Şimşek F, Tarcan T (2014) Urinary NGF, TGF-β1, TIMP-2 and bladder wall thickness predict neurourological findings in children with myelodysplasia. J Urol 191(1):199–205

    Article  PubMed  Google Scholar 

  17. Peyronnet B, Even A, Capon G, De Seze M, Hascoet J, Biardeau X et al (2018) Intradetrusor injections of botulinum toxin A in adults with spinal dysraphism. J Urol 200(4):875–880

    Article  CAS  PubMed  Google Scholar 

  18. Fry CH, Kitney DG, Paniker J, Drake MJ, Kanai A, Andersson K-E (2018) Fibrosis and the bladder, implications for function ICI-RS 2017. Neurourol Urodyn 37(S4):S7–S12

    Article  PubMed  Google Scholar 

  19. Hipp JA, Hipp JD, Yoo JJ, Atala A, Andersson K-E (2008) Microarray analysis of bladder smooth muscle from patients with myelomeningocele. BJU Int 102(6):741–746

    Article  PubMed  Google Scholar 

  20. Beqaj SH, Donovan JL, Liu DB, Harrington DA, Alpert SA, Cheng EY (2005) Role of basic fibroblast growth factor in the neuropathic bladder phenotype. J Urol 174(4 Pt 2):1699–1703

    Article  CAS  PubMed  Google Scholar 

  21. Janzen J, Vuong PN, Bersch U, Michel D, Zaech GA (1998) Bladder tissue biopsies in spinal cord injured patients: histopathologic aspects of 61 cases. Neurourol Urodyn 17(5):525–530

    Article  CAS  PubMed  Google Scholar 

  22. Vignozzi L, Gacci M, Maggi M (2016) Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol 13(2):108–119

    Article  CAS  PubMed  Google Scholar 

  23. Oztekin CV, Kaya-Sezginer E, Yilmaz-Oral D, Gur S (2018) Male urogenital disorders and metabolic syndrome: possible links, characteristics and potential treatment strategies. Curr Pharm Des 24(9):1019–1033

    Article  CAS  PubMed  Google Scholar 

  24. He Q, Wang Z, Liu G, Daneshgari F, MacLennan GT, Gupta S (2016) Metabolic syndrome, inflammation and lower urinary tract symptoms: possible translational links. Prostate Cancer Prostatic Dis 19(1):7–13

    Article  CAS  PubMed  Google Scholar 

  25. Fry CH, Sahai A, Vahabi B, Kanai AJ, Birder LA (2014) What is the role for biomarkers for lower urinary tract disorders? ICI-RS 2013. Neurourol Urodyn 33(5):602–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gamper M, Moser R, Viereck V (2017) Have we been led astray by the NGF biomarker data?: accurate NGF Assay? Neurourol Urodyn 36(1):203–204

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Hopital Pontchaillou, University of Rennes, 2 rue Henri Le Guilloux, 35000, Rennes, France

    Claire Richard, Juliette Hascoet, Quentin Alimi, Zine-eddine Khene, Andrea Manunta & Benoit Peyronnet

  2. Department of Biochemistry, University of Rennes, Rennes, France

    Claude Bendavid

  3. Department of Physical Medicine and Readaptation, Kerpape Institute, Ploemeur, France

    Jacques Kerdraon

  4. Department of Physical Medicine and Readaptation, University of Rennes, Rennes, France

    Caroline Voiry

  5. Department of Gastro-enterology, University of Rennes, Rennes, France

    Charlène Brochard, Guillaume Bouguen & Laurent Siproudhis

  6. Department of Urology, University of Toulouse, Toulouse, France

    Xavier Gamé

Authors
  1. Claire Richard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claude Bendavid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliette Hascoet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Quentin Alimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zine-eddine Khene
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacques Kerdraon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Caroline Voiry
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Charlène Brochard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guillaume Bouguen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Laurent Siproudhis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Andrea Manunta
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xavier Gamé
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Benoit Peyronnet
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CR: data collection, manuscript writing. CB: protocol development. JH: data collection. QA: data collection. ZEK: data analysis. JK: data collection, critical revision. CV: data collection, critical revision. CB: data collection, critical revision. GB: data collection, critical revision. LS: data collection, critical revision. AM: data collection, critical revision. XG: project development, supervision. BP: project development, data analysis, supervision

Corresponding author

Correspondence to Claire Richard.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethics board approval number: CER-1491_20141215.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Richard, C., Bendavid, C., Hascoet, J. et al. Urinary biomarkers profiles in patients with neurogenic detrusor overactivity according to their neurological condition. World J Urol 38, 2261–2268 (2020). https://doi.org/10.1007/s00345-019-03016-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-019-03016-x

Keywords

Search

Navigation