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Abstract: PO1846

Urinary Exosomal MicroRNAs Are Potential Diagnostic and Prognostic Biomarkers in IgA Nephropathy Patients

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Jeong, Kyung hwan, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kim, Jin sug, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Hwang, Hyeon Seok, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kong, Ji Yoon, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kang, Shinyeong, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Ra, Ri, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Kim, Yang gyun, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Moon, Ju young, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
  • Lee, Sangho, Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea (the Republic of)
Background

Micro-RNAs (miRNAs) are small non-coding RNA molecules which regulate disease pathophysiology by modulating target gene expression. miRNAs are derived from tissues and biofluids such as serum, saliva, and urine. Recently, emerging evidence suggests urinary exosomal miRNAs as non-invasive biomarkers of various kidney diseases. However, few studies investigated clinical relevance of miRNA in IgA nephropathy (IgAN). In this study, we evaluated urinary exosomal miRNA expression and analyzed its clinical significance in patients with IgAN.

Methods

Urine samples were collected from 93 patients with biopsy-proven IgAN and 14 normal controls. We identified mRNA differential expression of renal tissue between IgAN and normal subjects in the gene expression omnibus dataset, and selected 884 glomerular and 67 tubulointerstitial genes through meta-analysis. We then used the miRTarBase, TargetScan, micorRNA database to predict potential miRNA targets. Finally, 11 urinary exosomal miRNAs were selected. We observed urinary exosomal expression of miRNAs and analyzed their diagnostic and prognostic accuracy for IgAN.

Results

The expression of miR-16-5p, miR-26b-3p, miR-29a-3p, miR-29c-3p, miR-126-3p, miR-199a-3p, miR-615-3p, and miR-29b-3p were significantly upregulated in IgAN patients as compared with normal controls. miR-16-5p, miR-26b-3p, miR-29a-3p, miR-29c-3p, miR-126-3p, miR-199a-3p, and miR-29b-3p have good diagnostic accuracy of IgAN (area under curve of the receiver operating characteristic curve > 0.8). Baseline renal function significantly correlated with miR-16-5p, miR-29a-3p, miR-199a-3p, miR-199b-5p, miR-335-3p, and miR-615-3p. During follow-up period, 43 (46.2%) IgAN patients experienced adverse renal outcomes defined as a greater than 25% reduction in estimated glomerular filtration rate (eGFR), decline in eGFR category from the value determined at the time of renal biopsy, or start renal replacement therapy. miR-16-5p, miR-29a-3p, miR-199a-3p, and miR-335-3p were independently associated with increased risk of adverse renal outcomes.

Conclusion

Urinary exosomal miRNAs might be potential non-invasive biomarkers for diagnosis and prediction of disease progression of IgAN. Further studies are needed to clarify our results and ascertain the underlying mechanisms.