title: Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study.
abstract: Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; atin1@jhu.edu.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tin
authors.affiliation: Division of Nephrology, and.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Grams
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Foram N
authors.initials: FN
authors.lastname: Ashar
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota;
authors.forename: John A
authors.initials: JA
authors.lastname: Lane
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Federick, Maryland; Children's National Medical Center, Washington, DC; and.
authors.forename: Avi Z
authors.initials: AZ
authors.lastname: Rosenberg
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Grove
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota;
authors.forename: Nathan
authors.initials: N
authors.lastname: Pankratz
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland;
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000150:complications*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial
keywords: chronic kidney disease; epidemiology and outcomes; mitochondria; renal function decline