Urinary mitochondrial DNA is a useful biomarker for assessing kidney injury of antineutrophil cytoplasmic antibody -associated vasculitis

Clin Chim Acta. 2020 Mar:502:263-268. doi: 10.1016/j.cca.2019.11.014. Epub 2019 Nov 20.

Abstract

Background: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated.

Methods: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed.

Results: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74 ± 1859.72 vs. 474.90 ± 123.59 copy/nmol creatinine, p < 0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23 ± 1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R = 0.661, P < 0.001) and negatively correlated with estimated glomerular filtration rate (R = -0.515, P = 0.001). The urinary mtDNA level of crescentic class (4703.08 ± 1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14 ± 1158.99 copy/nmol creatinine) and focal class (2268.15 ± 1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R = 0.471, P = 0.048) and glomerular neutrophils (R = 0.673, P = 0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20 ± 1174.64 vs. 3795.67 ± 893.34 copy/nmol creatinine, p = 0.047).

Conclusions: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.

Keywords: ANCA; Histopathologic classification; Kidney biopsy; Myeloperoxidase; Urinary mtDNA.

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / urine*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / diagnosis
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / metabolism
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / urine*
  • Biomarkers / metabolism
  • Biomarkers / urine
  • DNA, Mitochondrial / metabolism
  • DNA, Mitochondrial / urine*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Lipocalin-2 / metabolism
  • Lipocalin-2 / urine
  • Male
  • Middle Aged
  • Peroxidase / metabolism
  • Peroxidase / urine

Substances

  • Biomarkers
  • DNA, Mitochondrial
  • Lipocalin-2
  • Peroxidase