PDF(Pubmed)
Abstract：
Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.
摘要：
糖尿病肾病（DKD）是2型糖尿病（T2DM）患者发病和死亡的主要原因。这项研究的目的是调查白蛋白结构改变是否与DKD严重程度相关，并评估天然和降低的白蛋白浓度是否可以补充DKD的诊断。为此,评估了117例无（n=42）和有（n=75）DKD（根据KDIGO分类的DKDI-III）的T2DM患者；通过溴甲酚绿测定法定量总白蛋白浓度（tHA），而结构改变通过液相色谱-高分辨率质谱（LC-HRMS）进行分析。天然白蛋白(eHA，随后评估有效白蛋白）和还原白蛋白（rHA）。HRMS分析显示DKD患者中天然白蛋白的相对量减少，并且改变形式的丰度增加，尤其是那些带有氧化修饰的。因此，在进展性肾衰竭阶段，eHA和rHA值都不同，这些改变与肾功能障碍呈剂量依赖性相关。ROC曲线分析显示，eHA和rHA诊断DKD的敏感性和特异性明显高于tHA。重要的是,根据多变量逻辑回归分析，eHA被确定为DKD的独立预测因子。
