Could urinary nerve growth factor and bladder wall thickness predict the treatment outcome of children with overactive bladder?

Abstract

Objective: Bladder wall thickness (BWTh) measurements and Nerve Growth Factor (NGF) /creatinine (Cr) values, as noninvasive tools, were found to predict daytime voiding problems in children with overactive bladder (OAB). The goal of this research was to examine if bladder wall thickness together with urine NGF/Cr could be a clinical utility in treatment outcome of OAB in children. Patients and Methods: A total of 60 children with OAB, (Group 1; n=40) and healthy normal controls (Group 2; n=20), aged 6-14 years old were involved in this prospective study. Children were evaluated with detailed history and physical examination, including neurologic examination, and were asked to complete a self-reported questionnaire and a 3-day bladder diary with the aid of their parents. Urofl owmetry was performed in all cases. Urinary nerve growth factor levels were measured by the ELISA and BWTh was measured trans-abdominally by one uro-radiologist specialized in pediatric ultrasonography. Urinary NGF levels were normalized by urinary creatinine levels and compared among all subgroups. Children with OAB received urotherapy as fi rst line treatment at least for three months. 18 children refractory to urotherapy received anticholinergic therapy defi ned as group 3. Results: The median age of the study group was 10 (range 6 to 16). After urotherapy, 22 children had similar BWTh and NGF/Cr values compared to controls. (2.75 ± 1.15; 2.40 ± 1.00 mm; p=0.86 and 1.02 ± 0.10; 0.78 ± 0.15; p=0.12, respectively). After anticholinergic treatment, BWTh levels (2.25 ± 0.90; 2.40 ± 1.00 mm; p=0.94) and NGF/Cr values (0.95 ± 0.10; 0.78 ± 0.15; p=0.42, respectively) had no signifi cantly difference compared to controls (Group 2). In receiver operating characteristic analysis, bladder wall thickness was found to have sensitivity of 85% and specifi city of 84.2% (3,20 AUC ,913; 95 %) and NGF/Cr had sensitivity of 90% and specifi city of 92.1% (1,595; AUC ,947; 95 %) in predicting treatment outcome in children with OAB. Conclusions: Bladder wall thickness measurements and NGF/Cr values, as noninvasive tools, could guide outcomes in the treatment of children with overactive bladder.

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

“…The average score was 3.91+/−0.56. The level of evidence was found as B for 13 (81.25%) articles 9–14,16–18,20,22–24 and C for 3 (18.75%) articles 15,19,21 …”

“…In six studies conducted with children with OAB, urinary NGF levels were found to be higher than the control group in five studies. 9,12,16,17,23 Also, one of them showed that urinary NGF values were found to be higher in children with urodynamically proven detrusor overactivity compared to healthy controls. 12 However, in one study, no relationship was found between OAB and urinary NGF levels.…”

“…[10][11][12][13]19,20,22,23 Only one biomarker was studied in 10 (62.5%) studies, 9,10,[12][13][14][17][18][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][10][11][12][13][14][15][16][17]20,[22][23][24] Brain-Derived Neurotrophic Factor (BDNF) in 5, 16,[20][21][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 While urinary biomarkers were measured by ELISA method in 15 studies, only Aqu...…”

“…Etiology Neurogenic LUTD 5 (31.25%) [10,11,15,19,21] Non-neurogenic LUTD 11 (68.75%) [9, 12-14, 16-18, 20, 22-24] Study design Observational studies 8 (50%) [9, 14-18, 21, 24] Cross-sectional 8 (50%) [10-13, 19, 20, 22, 23] Number thickness and NGF. 12,23 Cut-off values for urinary NGF were given in two studies: These were >5.8 pg/mg 12 and >360 pg/mL. 16 However, one study reported that urinary NGF and BDNF were not effective in the diagnosis and follow-up of children with OAB.…”

“…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.…”