Identification of diabetic kidney disease biomarkers via iTRAQ plasma proteomics analysis

Diabetic kidney disease (DKD) is a major diabetic complication that often progresses to end-stage renal disease and causes high mortality. Early diagnosis is essential for effective prevention and treatment. To explore the underlying mechanisms of DKD and identify plasma biomarkers for early diagnosis. In this study, healthy adults and individuals with diabetes mellitus (classified into normal albuminuria (NA), microalbuminuria (MI), and macroalbuminuria (MA) groups) were recruited. Plasma samples were collected from all participants, and 12 subjects per group were then randomly selected as a discovery cohort for proteomic analysis. Proteomics identified 95 differentially expressed proteins (DEPs) among the groups. These DEPs associated pathways evolved in a stage-specific manner in which inflammation dominated the early NA/Ctrl stage, complement and coagulation cascades became the main drivers during MI/NA, and MA/MI exhibited newly emerged disturbances in oxidative detoxification, lysosomal function, and nitrogen metabolism alongside sustained complement and coagulation changes. Among them, the complement and coagulation cascades were closely related to DKD progression. Through hub protein analysis, five proteins (FGG, ITIH4, A2M, C3, and APOE) that showed consistent trends across disease stages were identified as potential diagnostic biomarkers for DKD. Our research provides new insights into the mechanisms and early diagnosis of DKD.