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Abstract: TH-PO811

Patients with Immunoglobulin A Nephropathy Is Associated with Elevated Urinary Mitochondrial DNA Copy Number

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Yu, Byung chul, Soonchunhyang University Bucheon Hospital, Bucheon, Korea (the Republic of)
  • Kim, Hyoungnae, Soonchunhyang University Seoul Hospital, Seoul, Korea (the Republic of)
  • Park, Samel, Soonchynhyang University Cheonan Hospital, Cheonan, Korea (the Republic of)
  • Park, Moo Yong, Soonchunhyang University Bucheon Hospital, Bucheon, Korea (the Republic of)
  • Kwon, Soon hyo, Soonchunhyang University Seoul Hospital, Seoul, Korea (the Republic of)
Background

Urinary mitochondrial DNA (mtDNA) levels are considered to reflect mitochondrial injury in kidney. However, mitochondrial injury in IgA nephropathy (IgAN) remains unknown. We hypothesized that IgAN would be associated with increased urinary mtDNA copy numbers.

Methods

We prospectively enrolled age-sex matched healthy volunteers (HV) and biopsy-proven IgAN (n=30 each). 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 measured also urinary ND-1 and COX3 3 months after medical treatment in IgAN (n=12).

Results

The mean estimated glomerular filtration rate (eGFR) was significantly lower in IgAN compared with HV (75.2±28.8 vs 107.2±12.1 mL/min/1.73m2, respectively, p<0.001). log10ND1/nDNA and log10COX3/nDNA were significantly higher in IgAN compared with HV (5.70±0.36 vs 5.14±0.34, 5.68±0.37 vs 5.15±0.33 copies/μl of urine/nDNA, respectively, both p<0.001). There was no significant relation between urinary mtDNA copy numbers and tranditional prognostic markers at presentation in IgAN such as mean arterial pressure, eGFR, and the amount of proteinuria. In the M score of the Oxford classification, log10ND1/nDNA and log10COX3/nDNA were significantly lower in IgAN patients with mesangial hypercellularity (5.61±0.39 vs 5.89±0.20, p=0.014, 5.60±0.41 vs 5.85±0.16 copies/μl of urine/nDNA, p=0.022, respectively). Medical treatment did not reduced urinary mtDNA copy numbers.

Conclusion

Urinary mtDNA copy numbers were elevated in patients with IgAN. This suggests mitochondrial damage would be a pathogenesis in IgAN.

Relation between urinary mtDNA levels and clinical variables in patients with immunoglobulin A nephropathy
VariablesMean arterial pressureEstimated glomerular filtration rateProteinuria
log10ND1/nDNA levelr = -0.072, P = 0.706r = 0.147, P = 0.438r = -0.073, P = 0.701
log10COX3/nDNA levelr = -0.047, P = 0.805r = 0.125, P = 0.511r = -0.010, P = 0.957

Data were analyzed by Spearman’s rank correlation coefficient. COX3, cytochrome-c oxidase-3; mtDNA, mitochondrial DNA; ND1, nicotinamide adenine dinucleotide dehydrogenase subunit-1.