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神经生长因子(NGF):用于诊断膀胱过度活动症(OAB)的潜在尿液生物标志物?

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

机构信息

Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.

出版信息

BJU Int. 2013 Mar;111(3):372-80. doi: 10.1111/j.1464-410X.2012.11672.x.

Abstract

UNLABELLED

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised.

OBJECTIVE

To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB).

METHOD

A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF.

RESULTS

There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples. In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. However, raised levels are not limited to OAB, which questions its specificity. Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating. Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool.

CONCLUSIONS

Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost- and time-effectiveness. Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role.

摘要

目的

综述目前关于尿神经生长因子(NGF)作为一种潜在的膀胱过度活动症(OAB)生物标志物的研究。

方法

使用 PubMed 数据库进行全面的电子文献检索,以确定与尿 NGF 相关的出版物。

结果

有越来越多的出版物测量了不同类型膀胱功能障碍患者的尿 NGF 水平。这些包括 OAB、膀胱疼痛综合征、特发性和神经性逼尿肌过度活动、膀胱过度敏感和膀胱流出道梗阻。与健康对照组相比,这些病理状态下的尿 NGF 水平似乎升高。在 OAB 患者中,这些升高的尿 NGF 水平似乎在成功接受抗毒蕈碱药物和肉毒杆菌毒素 A 治疗后降低,这表明其在监测治疗反应方面具有潜在用途。然而,升高的水平并不仅限于 OAB,这质疑了其特异性。尿 NGF 测量采用酶联免疫吸附试验,使用针对 NGF 的多克隆抗体进行。该技术需要标准化,并且需要对不同的 NGF 抗体进行验证。在将其用作诊断和预后工具之前,还需要确定什么是尿 NGF 的“正常”范围。

结论

虽然在 OAB 中尿 NGF 增加的证据似乎令人信服,但关于其有效性的许多问题仍然存在,包括:特异性、敏感性、成本效益和时间效益。在这个分子被考虑用于这个角色之前,仍然需要评估和满足许多关于生物标志物的标准。

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