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Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis

  • Yosuke Morizawa 1,
  • Katsuya Aoki 1,
  • Yusuke Iemura 1,
  • Shunta Hori 1,
  • Daisuke Gotoh 1,
  • Shinji Fukui 1,
  • Yasushi Nakai 1,
  • Makito Miyake 1,
  • Kazumasa Torimoto 1,
  • Nobumichi Tanaka 1,
  • Kiyohide Fujimoto 1
1 Department of Urology, Nara Medical University, Nara, Japan

Publication: Neurourology Urodynamics, August 2019

DOI: doi.org/10.1002/nau.24142





Aim

To determine the urinary levels of nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) in children with monosymptomatic nocturnal enuresis (MNE) and evaluate whether these factors can be used as biomarkers for the treatment outcome.

Methods

NGF and BDNF levels were measured and compared in 38 children (28 boys and 10 girls) with MNE and 25 children (18 boys and 7 girls) with no urinary symptoms were assessed. The mean ages in the patient and control groups were 9 and 10 years, respectively (P = .49). The patients were treated with either alarm or desmopressin therapy.

Results

The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the patient group than in the control group (P = .0003 and P = .0095, respectively). NGF and BDNF levels showed a significant positive correlation (P = .0020, r = 0.40). With respect to the degree of response, 19 patients (50%) showed complete response (CR) or partial response (PR), and 19 patients (50%) showed nonresponse (NR). The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the NR group than in the CR and PR groups (P = .0003 and P = .0003, respectively).

Conclusions

Urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in children with MNE than in healthy controls. Urinary NGF/creatinine can be predictive factors of a poor treatment outcome in children with MNE.


Commentary by Prof. Konstantinos Kamperis

The treatment of nocturnal enuresis can be a demanding task for those children who do not respond to the two established first line treatments, the conditional alarm and desmopressin. Clinicians often commence their young patients to a number of treatments including multimodal treatments in a try and error approach. This reflects our lack of predictive factors that would enable us physician to tailor the treatment to each patient’s needs. The study by Morizawa et al addresses this issue. The investigators assessed nerve growth factor and brain derived growth factor both neurotrophic factors that have been implicated in bladder and development and function as predictors of treatment response in children with monosymptomatic enuresis. Patients (38 children) were found to share higher levels than controls (20 children). Moreover, the children refractory to desmopressin of the enuresis alarm were found to have even higher levels of NGF and the authors hypothesize that reflects bladder dysfunction in these children, a plausible hypothesis as maximal bladder volumes were also reduced.

This is an interesting study, not only for NGF ‘s potential as prognostic factor for response but also because it adds to our knowledge on the pathophysiology of enuresis. Further studies will hopefully elucidate the role of NGF in bladder function and dysfunction in enuresis.