Association Between Albumin Alterations and Renal Function in Patients With Type 2 Diabetes Mellitus

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM). 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 aim, one hundred and seventeen T2DM patients without (n=42) and with (n=75) DKD (DKD I-III upon KDIGO classification) were evaluated; total albumin concentration (tHA) was quantified by bromocresol green assay, while structural alterations were profiled assessed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The concentrations of albumin in native (eHA, effective albumin) and reduced (rHA) forms were then assessed. HRMS analyses showed 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 along the stages of progressive renal failure, and alterations dose-dependently correlated with renal dysfunction. ROC curves analysis showed a significantly higher sensitivity and specificity of eHA and rHA with respect to tHA for the diagnosis of DKD. Importantly, at multivariable logistic regression analysis, eHA was identified as independent predictor of DKD.