“…Moreover, pathway analysis of the differential proteins quantified in IgAN and healthy donors using DAVID with the KEGG database showed that “lysosome” ( P = 3.24 × 10 –6 ) and “extracellular membrane (ECM)–receptor interaction pathway” ( P = 2.55 × 10 –5 ) were two major pathways that were closely related to cell injury and the progression of renal fibrosis. , Finally, the biological implications of the significantly upregulated proteins were studied. Among them, as high as 38.3% of the 47 significantly upregulated proteins (Table S4) such as AFM, ORM1, CP, SERPINA1, and C3 were previously reported to be closely related to IgAN. − Besides, among the proteins that were not previously found to have a direct association with IgAN, carbonic anhydrase 1 (CA1, 47.5 times, P = 6.51 × 10 –6 ), desmocollin-1 (DSC1, 5.51 times, P = 0.000683), tissue α- l -fucosidase (FUCA1, 3.15 times, P = 0.00297), and peroxiredoxin-2 (PRDX2, 2.85 times, P = 0.00484) were reported to play important roles in prevention of oxidative damage, regulation of basal immunity, and function of kidney injury. − Further validation of the relationship between such proteins with IgAN is ongoing. All of the results demonstrated that the NIEV strategy would provide a new tool for highly efficient EV isolation that would enable the screening of specific disease biomarkers for disease diagnosis and monitoring.…”