Urinary neurotrophic peptides in postmenopausal women with and without overactive bladder

Pennycuff, Jon F.; Schutte, Stacey C.; Hudson, Catherine; Karp, Deborah R.; Malykhina, Anna P.; Northington, Gina M.

doi:10.1002/nau.23011

Cited by 18 publications

(16 citation statements)

References 24 publications

(47 reference statements)

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“…It is thought that NGF, which is overexpressed in pathological bladder, has a knock on effect to sensitise afferent C‐fibres, leading to sensory urgency, and ultimately reflex bladder hyperactivity, causing urinary frequency and urgency UI. However, in a recent published cross‐sectional study, no significant difference was found between OAB and healthy control subjects after controlling the confounding factors as much as possible in postmenopausal women …”

Section: Discussionmentioning

confidence: 90%

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Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis

Wei¹,

Zhang

Ruth³

2017

Neurourology and Urodynamics

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A total of 17 published studies were included in this meta-analysis. Among the studies considered, patients with OAB had a significant higher baseline urinary NGF/Cr (NGF normalized to urine creatinine) level compared to those of controls (SMD = 0.74, 95%CI = 0.43-1.04, P < 0.00001). After treatment, the level of NGF/Cr decreased significantly in OAB group. However, there was no significant difference between patients with IC (interstitial cystitis)/PBS (painful bladder syndrome) and patients with overactive bladder (OAB) with regard to the urinary NGF/Cr level (SMD = 0.18, 95%CI = -0.06 to 0.41, P = 0.14). There was a statistically significant heterogeneity among included studies (P < 0.00001, I = 85%). No obvious evidence of significant publication bias was detected. In conclusion, this meta-analysis indicates that urine NGF/Cr may be a useful biomarker for OAB in the future. Because of lack of specificity, it seems that NGF/Cr cannot be used as a biomarker for OAB at present. Nevertheless, combined with other biological indicators may improve its specificity in diagnosis. More high quality studies that control the compounding factors strictly should be conducted in the future.

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Section: Discussionmentioning

confidence: 90%

“…. There were 17 published studies eventually included in our meta‐analysis. The 17 studies (1 cross‐sectional study and 16 case‐control studies) included 1678 subjects in total (1137 patients, 541 controls).…”

Section: Resultsmentioning

confidence: 99%

Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis

Wei¹,

Zhang

Ruth³

2017

Neurourology and Urodynamics

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“…To date, several potential OAB biomarkers have been identified in both pre-clinical and clinical studies, including CGRP, ERK1/2, OTC3, VAChT, BDNF, and NGF [22,72,[94][95][96][97][98]. In this regard, the authors aimed to establish whether the administration of O-1602 is able to eradicate RA-induced disturbances in the levels of OAB markers in the bladder urothelium, detrusor muscle, and/or urine in female rats.…”

Section: Biochemical Studiesmentioning

confidence: 99%

A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors

et al. 2020

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The aim of the research was to assess the impact of O-1602—novel GPR55 and GPR18 agonist—in the rat model of detrusor overactivity (DO). Additionally, its effect on the level of specific biomarkers was examined. To stimulate DO, 0.75% retinyl acetate (RA) was administered to female rats’ bladders. O-1602, at a single dose of 0.25 mg/kg, was injected intra-arterially during conscious cystometry. Furthermore, heart rate, blood pressure, and urine production were monitored for 24 h, and the impact of O-1602 on the levels of specific biomarkers was evaluated. An exposure of the urothelium to RA changed cystometric parameters and enhanced the biomarker levels. O-1602 did not affect any of the examined cystometric parameters or levels of biomarkers in control rats. However, the O-1602 injection into animals with RA-induced DO ameliorated the symptoms of DO and caused a reversal in the described changes in the concentration of CGRP, OCT3, BDNF, and NGF to the levels observed in the control, while the values of ERK1/2 and VAChT were significantly lowered compared with the RA-induced DO group, but were still statistically higher than in the control. O-1602 can improve DO, and may serve as a promising novel substance for the pharmacotherapy of bladder diseases.

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“…Interestingly, Pennycuff et al could not find differences in urinary NGF levels between OAB and controls, but this was not discussed in detail by Sheng et al Furthermore, two publications using alternative NGF‐ELISAs (from Meso Scale Discovery (Rockville, MD) or PeproTech Inc (Rocky Hill, NJ)) also reported no differences in urinary NGF levels for cases (bladder pain syndrome/interstitial cystitis, OAB, or neurogenic lower urinary tract dysfunction) and controls. In fact, NGF concentrations were below detection level (10 pg/mL), indicating that current ELISA technology was not sensitive enough to detect NGF in urine.…”

mentioning

confidence: 97%

“…The Promega assay did not detect NGF, but other urinary components, such as immunoglobulin G, and in 2014, it was withdrawn from the market. The remaining four studies used NGF‐ELISAs from Wuhan Boster Biological Technology, Ltd. (Wuhan, China), from RayBiotech (Norcross, GA), and from a not‐specified provider …”

mentioning

confidence: 99%

Re: Sheng W, Zhang H, Kirschner‐Hermanns R. Could urinary nerve growth factor be a biomarker for overactive bladder? A meta‐analysis. Neurourol Urodyn. 2017;9999:1–8. doi: 10.1002/nau.23210

Gamper

Viereck

2017

Neurourology and Urodynamics

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Sheng et al (Neurourology and Urodynamics 2017; DOI: 10.1002/nau.23210) presented a meta-analysis based on 17 publications to show that urinary nerve growth factor (NGF) may be a useful biomarker for overactive bladder syndrome (OAB). Unfortunately, 13 of the 17 studies used an unspecifc enzyme-linked immunosorbent assay (ELISA), the Promega NGF Emax Immunoassay, to quantify NGF in urine. This assay did not detect NGF in urine, but other urinary components, such as immunoglobulin G, and in 2014, it was withdrawn from the market. With other NGF-ELISAs, urinary NGF concentrations were found to be below detection level for both, OAB and healthy controls. Currently, ELISA techniques are not sensitive enough to detect NGF in urine, and urinary NGF cannot be used as a biomarker for OAB.

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Urinary neurotrophic peptides in postmenopausal women with and without overactive bladder

Cited by 18 publications

References 24 publications

Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis

Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis

A Novel Alternative in the Treatment of Detrusor Overactivity? In Vivo Activity of O-1602, the Newly Synthesized Agonist of GPR55 and GPR18 Cannabinoid Receptors

Re: Sheng W, Zhang H, Kirschner‐Hermanns R. Could urinary nerve growth factor be a biomarker for overactive bladder? A meta‐analysis. Neurourol Urodyn. 2017;9999:1–8. doi: 10.1002/nau.23210

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