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Abstract: PO1831

Mitochondrial Injury May Be a Ubiquitous Finding in the Pathogenesis of Various Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Yu, Byung chul, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Park, Moo Yong, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Choi, Soo Jeong, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Kim, Jin kuk, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Hwang, Seung Duk, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
Background

Previous study showed that mitochondrial injury is associated with IgA nephropathy (IgAN). It is not clear whether mitochondrial injury is a unique finding in IgAN or a ubiquitous finding in various glomerulonephtiris (GN). To clarify this, we analyzed urinary mitochondrial DNA (mtDNA) levels and expression of the stimulator of interferon genes (STING) pathway activated by mtDNA leakage in various GN.

Methods

We prospectively enrolled age-sex matched healthy volunteers (HV) and biopsy-proven IgAN, minimal change disease (MCD), acute tubulointerstitial nephritis (ATIN), and minor glomerular abnormalities (MGA) (n=30, 8, 10, and 7 each, respectively). Urinary copy number of the mtDNA genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured by quantitative polymerase chain reaction. We analyzed STING expression in prostatic cancer specimen as control and kidney tissues obtained from each GN patients by immunohistochemistry staining.

Results

log10ND1/nDNA and log10COX3/nDNA were significantly higher in IgAN (p<0.001, p=0.002), MCD (p<0.001, both), ATIN (p<0.001, both), and MGA (p<0.001, both) compared with HV (Figure 1). Although there was a difference in signal intensity and site of kidney structures, positive staining for STING was observed in the kidney tissue of each GN patients. Characteristically, STING was strongly stained in the tubulointerstitium for ATIN and in the distal tubule for MGA (Figure 2).

Conclusion

Elevated urinary mtDNA copy numbers and STING activation were observed in various GN. These results suggest that mitochondrial injury would be a ubiquitous finding in the pathogenesis of various GN.

Funding

  • Government Support - Non-U.S.