Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

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...

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Veröffentlicht in:Journal of the American Society of Nephrology Jg. 27; H. 8; S. 2467
Hauptverfasser: Tin, Adrienne, Grams, Morgan E, Ashar, Foram N, Lane, John A, Rosenberg, Avi Z, Grove, Megan L, Boerwinkle, Eric, Selvin, Elizabeth, Coresh, Josef, Pankratz, Nathan, Arking, Dan E
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.08.2016
Schlagworte:
Aged
Atherosclerosis - complications
DNA Copy Number Variations
DNA, Mitochondrial - blood
DNA, Mitochondrial - genetics
Female
Humans
Male
Middle Aged
Prospective Studies
Renal Insufficiency, Chronic - blood
Renal Insufficiency, Chronic - epidemiology
Renal Insufficiency, Chronic - etiology
Risk Factors
chronic kidney disease
epidemiology and outcomes
renal function decline
mitochondria
ISSN:1533-3450, 1533-3450
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1533-3450
1533-3450
DOI:10.1681/ASN.2015060661