Exosomal miR-4639 and miR-210 in Plasma and Urine as Biomarkers in IgA Nephropathy

Abstract

Background: It has been widely recognized that exosomal miRNAs can participate in the pathogenesis of different renal disorders and serve as disease biomarkers. Although kidney biopsy is still the gold standard for diagnosing and monitoring immunoglobulin A nephropathy (IgAN), it is highly required to identify new and effective noninvasive biomarkers for IgAN, the most frequently detected primary glomerulonephritis worldwide. Methods: Plasma and urinary exosomes were extracted by PEG precipitation. Size and morphological characteristics of plasma and urinary exosomes were observed by transmission electron microscopy and nanoparticle tracking analysis. The levels of plasma and urinary exosomes were revealed by Western blotting. The expressions of target miRNAs were revealed by in situ hybridization and qRT-PCR. Results: The levels of plasma and urinary exosomes were remarkably enhanced in IgAN patients compared with healthy controls (HCs). The expressions of miR-4639 and miR-210 in IgAN patients were significantly higher in contrast to the individuals with membranous nephropathy, minimal change nephrosis, diabetic nephropathy, or HC. These also played a valuable role in assessing the kidney function and the level of proteinuria. Furthermore, plasma and urinary exosomal miR-4639 expression was associated with more serious and active histological activity (mesangial hypercellularity, crescent, and C3 complement deposition). With an average follow-up of 8 months, miR-4639 and miR-210 expressions in plasma and urinary exosomes were higher in patients with progressive IgAN. Plasma exosomal miR-4639 and miR-210 were better than proteinuria (g/24 h) to estimate renal outcomes. Conclusion: Exosomal miR-4639 and miR-210 could be used as valid biomarkers to assist in diagnosis, evaluate severity, and assess disease development of IgAN.