Urinary brain-derived neurotrophic factor and nerve growth factor as noninvasive biomarkers of overactive bladder in children

Abstract

IntroductionOveractive bladder (OAB) is the most common urinary disorder and the leading cause of functional daytime intermittent urinary incontinence in children. The aim of this study was to determine whether urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations, normalized to urine creatinine, could be used as biomarkers for diagnosis and treatment monitoring of OAB in children. Materials and methodsUrine samples of 48 pediatric patients with OAB were collected at the start of anticholinergic therapy (baseline), at follow-up visits (3 and 6 months), and from 48 healthy controls. Urinary BDNF and NGF concentrations were determined by ELISA method (Merck, Darmstadt, Germany) and Luminex method (Thermo Fisher Scientific, Waltham, USA). Differences of frequency between quantifiable analyte concentrations between subject groups were determined using Fisher’s exact test. ResultsThere was no statistically significant difference between quantifiable analyte concentrations between patients at baseline and the control group for BDNF and NGF by either the ELISA or Luminex method (P = 1.000, P = 0.170, P = 1.000, and P = N/A, respectively). There was a statistically significant difference between quantifiable BDNF by the ELISA method between patients at baseline and complete success follow-up (P = 0.027), while BDNF by Luminex method and NGF by both methods were not statistically significant (P = 0.078, P = 0.519, and P = N/A, respectively). ConclusionsThis study did not demonstrate that urinary BDNF and NGF concentrations, can be used as biomarkers for diagnosis and therapy monitoring of OAB in children.

Urinary biomarkers in children with neurogenic and non‐neurogenic lower urinary tract dysfunction: A systematic review and meta‐analysis

“…18 In one study, urinary NGF and BDNF were also measured by the immunoassay (Luminex) method. 24 A control group was used in 11 (68.75%) studies 9,10,[12][13][14]16,17,20,[22][23][24] and invasive urodynamic evaluation was performed in 6 (37.5%) studies. [10][11][12]15,19,21 The most commonly studied urinary biomarker in children with LUTD dysfunction was found to be NGF.…”

“…While 8 studies (50%) were designed as observational trial, 9,14–18,21,24 8 (50%) were designed as cross‐sectional 10–13,19,20,22,23 . Only one biomarker was studied in 10 (62.5%) studies, 9,10,12–14,17–19,21,23 multiple biomarkers were evaluated in 6 (37.5%) studies 11,15,16,20,22,24 . Nerve Growth Factor (NGF) was evaluated in 13 studies, 9–17,20,22–24 Brain‐Derived Neurotrophic Factor (BDNF) in 5, 16,20–22,24 Tissue Inhibitor of Metalloproteinase‐2 (TIMP‐2) in 2, 11,15 Transforming Growth Factor Beta‐1 (TGF Beta‐1) in 2, 11,15 Neutrophil Gelatinase‐Associated Lipocalin (NGAL) in 1, 19 and Aquaporin‐2 in 1 18 .…”

“…Although it has been reported that urinary BDNF is effective in both the diagnosis and follow-up of children with OAB, 16 also there is a study claiming the opposite. 24 In addition, urinary BDNF was found to be correlated with MDSS. 16 It was observed that urinary BDNF was higher in children with MNE than in healthy children and decreased after treatment.…”

“…According to the Dutch Cochrane Checklist, 10 (62.5%) articles [9][10][11][12][13][14]16,19,20 were evaluated on 4 items and 6 (37.5%) articles 15,17,18,21,23,24 on 5 items (Table 3). The average score was 3.91+/−0.56.…”

“…The average score was 3.91+/−0.56. The level of evidence was found as B for 13 (81.25%) articles [9][10][11][12][13][14][16][17][18]20,[22][23][24] and C for 3 (18.75%) articles. 15,19,21 F I G U R E 2 Forest plot of comparison of urinary NGF between patient and control groups.…”