IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

IgA 肾病与尿液线粒体 DNA 拷贝数升高有关

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作者:Byung Chul Yu, Nam-Jun Cho, Samel Park, Hyoungnae Kim, Soo Jeong Choi, Jin Kuk Kim, Seung Duk Hwang, Hyo-Wook Gil, Eun Young Lee, Jin Seok Jeon, Hyunjin Noh, Dong Cheol Han, Yon Hee Kim, So-Young Jin, Moo Yong Park, Soon Hyo Kwon

Abstract

Mitochondrial injury plays important roles in the pathogenesis of various kidney diseases. However, mitochondrial injury in IgA nephropathy (IgAN) remains largely unexplored. Here, we examined the associations among mitochondrial injury, IgAN, and treatment outcomes. We prospectively enrolled patients with IgAN and age-/sex-matched healthy volunteers (HVs) as controls (n = 31 each). Urinary copy numbers of the mitochondrial DNA (mtDNA) genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured. Urinary mtDNA levels were elevated in the IgAN group compared with that in HVs (p < 0.001). Urinary ND1 levels were significantly higher in the low proteinuria group than in the high proteinuria group (p = 0.027). Changes in urinary levels of ND1 and COX3 were positively correlated with changes in proteinuria (p = 0.038 and 0.024, respectively) and inversely correlated with changes in the estimated glomerular filtration rate (p = 0.033 and 0.017, respectively) after medical treatment. Mitochondrial injury played important roles in IgAN pathogenesis and may be involved in early-stage glomerular inflammation, prior to pathological changes and increased proteinuria. The correlation between changes in urinary mtDNA and proteinuria suggest that these factors may be promising biomarkers for treatment outcomes in IgAN.

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