INTRODUCTION. IgA nephropathy (IgAN) has a highly variable clinical presentation and progression. Its diagnosis requires renal biopsy and the ability to accurately predict individual prognosis currently is limited. Therefore, the identification of biomarkers allowing non-invasive diagnosis and monitoring of disease is strongly required. We investigated urine proteome of IgAN patients in order to identify a set of proteins potentially helpful in distinguishing biopsy-proven IgAN patients.

MATERIALS AND METHODS. Urine proteins from 49 IgAN patients, 42 patients with non-IgA chronic nephropathies (CKD: 16 Diabetic Nephropathy, 12 Benign Nephroangiosclerosis and 14 Membranous Nephropathy) and 40 healthy individuals (CTRL) were run on CM10 chromatographic surface and analyzed by SELDI-TOF/MS. Mass peaks in the 3000-30000 m/z mass range were managed by univariate analysis. Mass peaks able to discriminate IgAN were isolated by 2D-PAGE and identified by MALDI-TOF-MS/MS. Proteomic findings were confirmed by Western Blot (WB) and immunonephelometry (IN) analysis of target proteins, whose expression in renal biopsies was explored by immunohistochemistry.

RESULTS AND CONCLUSIONS. Univariate analysis identified 13 mass peaks able to discriminate IgAN from CKD and CTRL. Among them, two mass peaks were identified as LG3 peptide and Ig-k light chains. WB analysis confirmed the decreased urinary excretion of LG3 in IgAN compared to CKD and CTRL (p=0.004, p<0.0005, respectively). Then, IN analysis confirmed the lower urinary excretion of kappa free LC in IgAN patients compared to CKD and CTRL (p=0.04, p=0.0002, respectively). Accordingly, tissue data showed an increase of k FLC deposition and a decrease of LG3 in IgAN biopsy specimens. Finally, urinary kappa FLC and LG3 inversely correlated with the severity of clinical and histologic features of IgAN patients.

In conclusion, urine proteome analysis is a powerful tool to distinguish IgAN patients from CKD patients and healthy subjects. Higher urinary level of k FLC and LG3 are associated to IgAN patients with a better prognosis. K FLC and LG3 peptide could serve as candidate non-invasive diagnostic and/or prognostic biomarkers of IgAN.