Item type: | Article | ||||||
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Journal or Publication Title: | Kidney Int. | ||||||
Publisher: | Elsevier | ||||||
Place of Publication: | NEW YORK | ||||||
Volume: | 96 | ||||||
Number of Issue or Book Chapter: | 2 | ||||||
Page Range: | pp. 480-488 | ||||||
Date: | August 2019 | ||||||
Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) | ||||||
Identification Number: |
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Keywords: | PERIPHERAL-BLOOD; MECHANISMS; STRESS; RISK; QUANTIFICATION; DYSFUNCTION; MODERATE; FISSION; HEALTH; TARGET; chronic kidney disease; infections; mitochondrial DNA copy number; mortality | ||||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||
Status: | Published | ||||||
Refereed: | Yes, this version has been refereed | ||||||
Created at the University of Regensburg: | Partially | ||||||
Item ID: | 40850 |
Abstract
Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for mitochondrial dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated with increased mortality and risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated the prognostic role of mtDNA copy number for cause-specific ...
Abstract
Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for mitochondrial dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated with increased mortality and risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated the prognostic role of mtDNA copy number for cause-specific mortality in 4812 patients from the German Chronic Kidney Disease study, an ongoing prospective observational national cohort study of patients with CKD stage G3 and A1-3 or G1-2 with overt proteinuria (A3) at enrollment. MtDNA was quantified in whole blood using a plasmid-normalized PCR-based assay. At baseline, 1235 patients had prevalent cardiovascular disease. These patients had a significantly lower mtDNA copy number than patients without cardiovascular disease (fully-adjusted model: odds ratio 1.03, 95% confidence interval [CI] 1.01-1.05 per 10 mtDNA copies decrease). After four years of follow-up, we observed a significant inverse association between mtDNA copy number and all-cause mortality, adjusted for kidney function and cardiovascular disease risk factors (hazard ratio 1.37, 95% CI 1.09-1.73 for quartile 1 compared to quartiles 2-4). When grouped by causes of death, estimates pointed in the same direction for all causes but in a fully-adjusted model decreased copy numbers were significantly lower only in infection-related death (hazard ratio 1.82, 95% CI 1.08-3.08). A similar association was observed for hospitalizations due to infections in 644 patients (hazard ratio 1.19, 95% CI 1.00-1.42 in the fully-adjusted model). Thus, our data support a role of mitochondrial dysfunction in increased cardiovascular disease and mortality risks as well as susceptibility to infections in patients with CKD.
Metadata last modified: 15 Mar 2022 09:50