Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Eur J Clin Invest. 2018 Jun;48(6):e12937. doi: 10.1111/eci.12937. Epub 2018 May 13.
Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end-stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop noninvasive, accurate detection markers.
MATERIALS & METHODS: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients and 21 healthy controls (HCs) were recruited. All participants' serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers.
From nano LC-MS and Western blot analysis, apolipoprotein A-IV (ApoA4) was selected which featured a gradual, almost twofold increase in the order of HC, DM and DN. In the Con A-based ELISA, the DM group was 1.91-fold higher than the HC group, while the DN group was 2.56-fold higher than the HCs and 1.33-fold higher than the DM group. In addition, significant positive correlations were observed between ApoA4 and blood urea nitrogen levels and between ApoA4 and creatine levels, while significant negative correlations were seen between serum protein levels and between serum albumin levels in comparisons of DM and DN samples.
Serum Con A-bound ApoA4 levels were higher in the DM group than in HCs, and further increased in the DN group. Levels of ApoA4 were positively correlated with blood urea nitrogen and creatine, but negatively correlated with serum protein and albumin. This evidence supports serum Con A-bound ApoA4 as a circulating marker for predicting the progression of renal impairment in DM patients.
在多种病因中,糖尿病肾病 (DN) 是导致终末期肾病 (ESRD) 的主要潜在肾脏疾病,早期诊断可以有效预防或延缓进展为 ESRD。因此,本研究旨在开发非侵入性、准确的检测标志物。
本研究纳入了 62 例糖尿病患者 (DM)、59 例糖尿病肾病患者 (DN) 和 21 名健康对照者 (HC)。所有参与者的血清样本均进行了伴刀豆球蛋白 A(Con A)亲和层析,利用糖蛋白来发现潜在的标志物。
通过纳诺 LC-MS 和 Western blot 分析,选择载脂蛋白 A-IV (ApoA4) 作为标志物,其特征是 HC、DM 和 DN 组依次呈逐渐增加趋势,几乎增加两倍。在 Con A 酶联免疫吸附测定 (ELISA) 中,DM 组比 HC 组高 1.91 倍,而 DN 组比 HC 组高 2.56 倍,比 DM 组高 1.33 倍。此外,ApoA4 与血尿素氮水平呈显著正相关,与肌酐水平呈显著正相关,而与 DM 和 DN 样本的血清蛋白水平呈显著负相关,与血清白蛋白水平呈显著负相关。
DM 组血清 Con A 结合的 ApoA4 水平高于 HC 组,DN 组进一步升高。ApoA4 水平与血尿素氮和肌酐呈正相关,与血清蛋白和白蛋白呈负相关。这一证据支持血清 Con A 结合的 ApoA4 作为预测 DM 患者肾功能损害进展的循环标志物。