School of Medicine, University of Notre Dame, Sydney, Australia.
National Centre for Neuroimmunology and Emerging Diseases (NCNED), Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
J Transl Med. 2023 Jul 5;21(1):440. doi: 10.1186/s12967-023-04295-0.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is currently no universal diagnostic marker or targeted treatment for ME/CFS. Urine is a non-invasive sample that provides biomarkers that may have the potential to be used in a diagnostic capacity for ME/CFS. While there are several studies investigating urine-based biomarkers for ME/CFS, there are no published systematic reviews to summarise existing evidence of these markers. The aim of this systematic review was to compile and appraise literature on urinary-based biomarkers in ME/CFS patients compared with healthy controls.
Three databases: Embase, PubMed, and Scopus were searched for articles pertaining to urinary biomarkers for ME/CFS compared with healthy controls published between December 1994 to December 2022. The final articles included in this review were determined through application of specific inclusion and exclusion criteria. Quality and bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A meta-analysis according to Cochrane guidelines was conducted on select studies, in particular, those that investigate urinary free cortisol levels in ME/CFS patients compared to healthy controls using the program STATA 17.
Twenty-one studies were included in this review. All of the studies investigated urinary-based markers in ME/CFS patients compared with healthy controls. The reported changes in urinary outputs include urinary free cortisol (38.10%), carnitine (28.6%), iodine (4.76%), and the metabolome (42.86%). In most cases, there was minimal overlap in the main outcomes measured across the studies, however, differences in urinary free cortisol between ME/CFS patients and healthy controls were commonly reported. Seven studies investigating urinary free cortisol were included in the meta-analysis. While there were significant differences found in urinary free cortisol levels in ME/CFS patients, there was also substantial heterogeneity across the included studies that makes drawing conclusions difficult.
There is limited evidence suggesting a consistent and specific potential urinary-based biomarker for ME/CFS. Further investigations using more standardised methodologies and more stringent case criteria may be able to identify pathophysiological differences with diagnostic potential in ME/CFS patients compared with healthy controls.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种多因素疾病，影响包括免疫系统、神经系统、内分泌系统、心血管系统和泌尿系统在内的许多身体系统。目前，ME/CFS 没有通用的诊断标志物或靶向治疗方法。尿液是一种非侵入性样本，提供的生物标志物有可能用于 ME/CFS 的诊断。虽然有几项研究调查了用于 ME/CFS 的基于尿液的生物标志物，但没有发表的系统评价来总结这些标志物的现有证据。本系统评价的目的是编译和评估与健康对照组相比，ME/CFS 患者尿液中生物标志物的文献。
在 Embase、PubMed 和 Scopus 三个数据库中搜索了 1994 年 12 月至 2022 年 12 月期间发表的关于与健康对照组相比，用于 ME/CFS 的尿液生物标志物的文章。通过应用特定的纳入和排除标准，确定本综述中包含的最终文章。使用 Joanna Briggs 研究所病例对照研究的批判性评估清单评估质量和偏倚。根据 Cochrane 指南对选定的研究进行了 meta 分析，特别是那些使用 STATA 17 程序比较 ME/CFS 患者与健康对照组尿液游离皮质醇水平的研究。
本综述纳入了 21 项研究。所有研究都调查了 ME/CFS 患者与健康对照组相比尿液中的生物标志物。报告的尿液输出变化包括尿游离皮质醇（38.10%）、肉碱（28.6%）、碘（4.76%）和代谢组学（42.86%）。在大多数情况下，研究之间测量的主要结果几乎没有重叠，但是，ME/CFS 患者和健康对照组之间的尿游离皮质醇差异通常有报道。纳入了 7 项研究尿游离皮质醇的 meta 分析。虽然 ME/CFS 患者的尿游离皮质醇水平存在显著差异，但纳入研究之间存在很大的异质性，这使得很难得出结论。
有有限的证据表明 ME/CFS 有一个一致和特定的潜在尿液生物标志物。使用更标准化的方法和更严格的病例标准进行进一步研究，可能能够识别 ME/CFS 患者与健康对照组相比具有诊断潜力的病理生理差异。
