Complement components, proteolysis‑related, and cell communication‑related proteins detected in urine proteomics are associated with IgA nephropathy.

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulonephritis. The first symptoms of IgAN are erytrocyturia or hematuria, proteinuria, and decline in renal function, or any combination of the above. One of the promising diagnostic methods is urine proteomics. We studied urine proteomics in patients with IgAN and age- and sex‑matched healthy controls. To minimize the risk of protein degradation, we proposed a new protocol for urine collection and preparation. A total of 30 patients with IgAN and 30 controls were enrolled into the study. Thirty urine samples of the IgAN group were divided into 3 disease pooled samples (DPS I, II, and III) and 30 urine samples of the control group were divided into 3 control pooled samples (CPS I, II, and III). We used isoelectric focusing/liquid chromatography-mass spectrometry/mass spectrometry (IEF/LC‑MS/MS) to detect all proteins larger than 10 kDa. Using qualitative analysis, we identified 761, 951, and 956 proteins in each of the 3 IEF/LC‑MS/MS experiments. The results were combined, yielding a dataset with 1238 proteins identified by at least 2 peptides. The statistical analysis of the quantitative results revealed 18 proteins that were differently populated in the urine of IgAN patients compared with healthy controls. We found increased urinary concentrations of complement components, coagulation factors, extracellular matrix, intracellular, transmembrane, and other proteins in patients with IgAN. Some of them have never been linked to IgAN before. We demonstrated that urine proteomics is a promising tool for diagnosing and monitoring patients with IgAN.