School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Division of Laboratory Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland.
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 May 15;1116:9-18. doi: 10.1016/j.jchromb.2019.03.031. Epub 2019 Mar 26.
The prevalence of chronic kidney disease (CKD) is increasing worldwide. New technical approaches are needed to improve early diagnosis, disease understanding and patient monitoring, and to evaluate new therapies. Metabolomics, as a prime candidate in the field of CKD research, aims to comprehensively analyze the metabolic complexity of biological systems. An extensive analysis of the metabolites contained in biofluids is therefore needed, and the combination of data obtained from multiple analytical platforms constitutes a promising methodological approach. This study presents an original workflow based on complementary chromatographic conditions, reversed-phase and hydrophilic interaction chromatography hyphenated to mass spectrometry to improve the polar metabolome coverage coupled with a univocal metabolite annotation strategy enabling a rapid access to the biological interpretation. This multiplatform workflow was applied in a CKD cohort study to assess plasma metabolic profile modifications related to renal disease. Multivariate analysis of 278 endogenous annotated metabolites enabled patient stratification with respect to CKD stages and helped to generate new biological insights, while also confirming the relevance of tryptophan metabolism pathway in this condition.
慢性肾脏病 (CKD) 的患病率在全球范围内正在不断增加。需要新的技术方法来改善早期诊断、疾病理解和患者监测，并评估新的治疗方法。代谢组学作为 CKD 研究领域的主要候选方法，旨在全面分析生物系统的代谢复杂性。因此，需要对生物体液中包含的代谢物进行广泛分析，并且来自多个分析平台的数据的组合构成了一种很有前途的方法学方法。本研究提出了一种基于互补色谱条件、反相和亲水相互作用色谱与质谱联用的原始工作流程，以提高极性代谢组学的覆盖范围，并结合一种明确的代谢物注释策略，能够快速进行生物学解释。该多平台工作流程应用于 CKD 队列研究中，以评估与肾脏疾病相关的血浆代谢谱变化。对 278 个内源性注释代谢物的多元分析能够根据 CKD 阶段对患者进行分层，并有助于产生新的生物学见解，同时也证实了色氨酸代谢途径在这种情况下的相关性。
