Urinary afamin levels are associated with the progression of diabetic nephropathy
Urinary afamin levels are associated with the progression of diabetic nephropathy
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DOI：
10.1016/j.diabres.2018.02.034
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发表时间：
2019-01-01
影响因子：
5.1
通讯作者：
Unoki-Kubota, Hiroyuki
中科院分区：
文献类型：
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作者：
Kaburagi, Yasushi;Takahashi, Eri;Unoki-Kubota, Hiroyuki
目标：本研究应用蛋白质组学定量分析技术，对2型糖尿病（T2 DM）患者尿蛋白进行定量分析。使用独立样本集（n = 77），通过多反应监测（MRM）分析测量排泄蛋白的尿液水平。采用ELISA法检测203例2型糖尿病和糖尿病肾病患者尿afamin水平。结果：104种蛋白质的排泄量有显著变化。这些候选人中有9人通过MRM分析进行了验证。其中，afamin、CD 44抗原和溶酶体相关膜糖蛋白2的水平与尿白蛋白/肌酐比值（ACR）和eGFR显著相关，而这些水平以前与DN无关。我们进一步测量了从尚未患有显著肾脏疾病的T2 DM患者收集的尿液中的afamin水平（ACR < 300 mg/g或eGFR变化率
Aims: In this study, we applied quantitative proteomic analysis to identify urinary proteins associated with diabetic nephropathy (DN).Methods: Two-dimensional image-converted analysis of liquid chromatography and mass spectrometry detected the proteins differentially excreted between normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by multiple reaction monitoring (MRM) analysis using an independent sample set (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients enrolled in this cohort study (n = 203).Results: One-hundred-four proteins displayed significant alterations in excretion. Nine of these candidates were validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and lysosome-associated membrane glycoprotein 2, which have not previously been implicated in DN, were significantly associated with both the urinary albumin to creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine collected from T2DM patients who did not yet have significant kidney disease (ACR < 300 mg/g or eGFR change rate