Department of Clinical Laboratory, University of Tokyo Hospital, Tokyo, Japan; Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Clinical Laboratory, University of Tokyo Hospital, Tokyo, Japan; Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Lipid Res. 2021;62:100120. doi: 10.1016/j.jlr.2021.100120. Epub 2021 Sep 22.
Diabetic nephropathy is a major complication of diabetes mellitus, and thus novel biomarkers are desired to evaluate the presence and progression of diabetic nephropathy. In this study, we sought to identify possible metabolites related to diabetic nephropathy among urinary eicosanoids and related mediators. Using liquid chromatogram-tandem mass spectrometry, we optimized the lipid extraction from urine using the Monospin C18 as a solid-phase extraction cartridge and measured the urinary lipid mediators in 111 subjects with type 2 diabetes mellitus as well as 33 healthy subjects. We observed that 14 metabolites differed significantly among the clinical stages of nephropathy. Among them, levels of tetranor-prostaglandin E metabolite (tetranor-PGEM), an arachidonic acid metabolite, were significantly higher in subjects with stage 1 nephropathy than in healthy subjects and increased with the progression of nephropathy. We also observed that levels of maresin-1, a docosahexaenoic acid metabolite, and leukotriene B4-ethanolamide, an arachidonoyl ethanolamide metabolite, were significantly lower in subjects with stage 3-4 nephropathy than in healthy subjects and those with stage 1-2 nephropathy. Finally, using a comprehensive analysis of urinary eicosanoids and related mediators, we concluded that tetranor-PGEM was capable of discriminating clinical stages of nephropathy and thus useful as a novel biomarker for diabetic nephropathy.
糖尿病肾病是糖尿病的主要并发症，因此需要新的生物标志物来评估糖尿病肾病的存在和进展。在这项研究中，我们试图在尿中的类二十烷酸及其相关介质中确定与糖尿病肾病相关的可能代谢物。我们使用液相色谱-串联质谱法，使用 Monospin C18 固相萃取小柱优化了尿液中的脂质提取，并测量了 111 例 2 型糖尿病患者和 33 例健康受试者的尿脂质介质。我们观察到，在肾病的临床阶段之间有 14 种代谢物差异显著。其中，四氢前列腺素 E 代谢物（tetranor-PGEM）的水平，一种花生四烯酸代谢物，在 1 期肾病患者中明显高于健康受试者，并随着肾病的进展而增加。我们还观察到，maresin-1 的水平，一种二十二碳六烯酸代谢物，和白三烯 B4-乙醇酰胺，一种花生四烯酰乙醇酰胺代谢物，在 3-4 期肾病患者中明显低于健康受试者和 1-2 期肾病患者。最后，通过对尿类二十烷酸及其相关介质的综合分析，我们得出结论，四氢前列腺素 E 代谢物能够区分肾病的临床阶段，因此可作为糖尿病肾病的一种新的生物标志物。
