IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

Yu, Byungchul; Cho, Namjun; Park, Samel; Kim, Hyoungnae; Choi, Soo Jeong; Kim, Jin Kuk; Hwang, Seung Duk; Gil, Hyo‐Wook; Lee, Eun Young; Jeon, Jin Seok; Noh, Hyunjin; Han, Dong Cheol; Kim, Yon Hee; Jin, So-Young; Park, Moo Yong; Kwon, Soon Hyo

doi:10.1038/s41598-019-52535-5

Cited by 17 publications

(20 citation statements)

References 44 publications

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“…Interestingly, when dividing the MGAs group into two subgroups according to urinary mtDNA levels, the subgroup of patients with higher mtDNA had a lower MAP and a trend of higher eGFR and lower proteinuria levels. These findings are consistent with our previous findings in patients with IgAN [17]. These results may indicate that mitochondrial damage is involved in the early stage of glomerular inflammation.…”

Section: Discussionsupporting

confidence: 94%

“…Mitochondrial injury plays an important role in the pathogenesis of various kidney diseases, including acute kidney injury [6], chronic kidney disease [7][8][9][10], obesity-related hyperfiltration [11], and glomerulonephritis (GN) [12][13][14][15][16]. Recently, we demonstrated that mitochondrial injury is involved in early-stage glomerular inflammation prior to pathological changes in immunoglobulin A nephropathy (IgAN) by measuring urinary mitochondrial DNA (mtDNA) [17], which is used as a surrogate marker of mitochondrial injury in various kidney diseases [18][19][20]. Based on this finding, we hypothesized that mitochondrial injury may exist prior to noticeable pathological changes in MGAs, and that MGAs are associated with the deterioration of kidney function.…”

Section: Introductionmentioning

confidence: 99%

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Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Cho

Park

et al. 2019

JCM

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Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age-and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Cho

Park

et al. 2019

JCM

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“…Kidney biopsy from a patient with IgAN showed mild focal segmental mesangial proliferation with dominant mesangial IgA deposition and an increased number of abnormal mitochondria in the proximal tubular cells [71]. Elevated urinary mtDNA levels were observed in patients with IgAN, and changes in urinary mtDNA were inversely correlated with eGFR [72]. Whole mitochondrial genome sequencing data from patients with IgAN who were renal transplant recipients revealed an association between five common single-nucleotide polymorphisms and ESRD, suggesting that mitochondrial defects play a potential role in the progression of CKD [73].…”

Section: Iga Nephropathymentioning

confidence: 95%

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Bhatia¹,

Capili²,

Choi

2020

Kidney Res Clin Pract

101

104

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Renal inflammation and tissue damage during acute kidney injury (AKI) and chronic kidney disease (CKD) have been linked to mitochondrial structural and functional alterations [1,2]. Mitochondria are a highly complex interconnected network of organelles that fulfill cellular energy needs. The kidney, an organ with high energy demands, is rich in mitochondria. Mitochondrial dysfunction arising from disturbances in the regulation of the mitochondrial electron transport chain (ETC), proton gradient, and membrane potential results in reduced adenosine triphosphate (ATP) and increased production of mitochondrial-derived reactive oxygen species (mROS), which promotes kidney injury and inflammation [3,4].

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“…Because urine samples are not invasive and can be obtained repeatedly during the follow-up period, urinary biomarkers have the advantage of being easy to analyze. Various studies are being conducted to discover and validate urinary biomarkers that can predict IgAN prognosis [27][28][29][30]. In this context, recent studies on the efficacy of urinary C5b-9 as a biomarker in IgAN were conducted, and urinary C5b-9 levels increased in patients with IgAN compared with healthy volunteers and were associated with disease severity and inversely correlated with eGFR in patients with IgAN [16,24].…”

Section: Discussionmentioning

confidence: 99%

Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy

Park

Lee

et al. 2022

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C5b-9 plays an important role in the pathogenesis of immunoglobin A nephropathy (IgAN). We evaluated C5b-9 as a prognostic marker for IgAN. We prospectively enrolled 33 patients with biopsy-proven IgAN. We analyzed the correlation between baseline urinary C5b-9 levels, posttreatment changes in their levels, and clinical outcomes, including changes in proteinuria, estimated glomerular filtration rate (eGFR), and treatment response. Baseline urinary C5b-9 levels were positively correlated with proteinuria (r = 0.548, p = 0.001) at the time of diagnosis. Changes in urinary C5b-9 levels were positively correlated with changes in proteinuria (r = 0.644, p < 0.001) and inversely correlated with changes in eGFR (r = −0.410, p = 0.018) at 6 months after treatment. Changes in urinary C5b-9 levels were positively correlated with time-averaged proteinuria during the follow-up period (r= 0.461, p = 0.007) but were not correlated with the mean annual rate of eGFR decline (r = −0.282, p = 0.112). Baseline urinary C5b-9 levels were not a significant independent factor that could predict the treatment response in logistic regression analyses (odds ratio 0.997; 95% confidence interval, 0.993 to 1.000; p = 0.078). Currently, urinary C5b-9 is not a promising prognostic biomarker for IgAN, and further studies are needed.

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IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

Cited by 17 publications

References 44 publications

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches

Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy

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