Clinical Significance of Urinary Exosomal microRNAs in patients with IgA nephropathy

Abstract

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. Methods: From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathological features. The primary endpoint of this study was to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Results: IgAN group showed dysregulated urinary exosomal miRNA levels compared with the normal and disease control groups. Urinary exosomal miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate analysis, age, body mass index, hypertension, eGFR, uPCR, and five miRNAs (miR-16-5p, miR-29a-3p, miR-124-3p, miR-199a-3p, and miR-335-3p) were significantly associated with disease progression in patients with IgAN. MiR-199a-3p with the lowest p-value in disease progression analysis, showed an area under the curve (AUC) of 0.727, while the AUC of miR-124-3p, with the second lowest p-value, was 0.718. When these two miRNAs were combined, the AUC was high enough (0.786), considering that the AUC of the International IgAN Risk Prediction Tool was 0.890. Conclusion: Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN. Further studies are needed to elucidate the physiological mechanisms and clarify the results of this study.