Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease

Journal article


Publication Details

Author(s): Fazzini F, Lamina C, Fendt L, Schultheiss UT, Kotsis F, Hicks AA, Meiselbach H, Weissensteiner H, Forer L, Krane V, Eckardt KU, Köttgen A, Kronenberg F, Schneider M, Dienemann T, Prokosch HU, Bärthlein B, Beck A, Ganslandt T, Reis A, Ekici AB, Avendaño S, Becker-Grosspitsch D, Alberth-Schmidt U, Hausknecht B, Zitzmann R, Weigel A, Walz G, Schultheiß U, Meder S, Mitsch E, Reinhard U, Floege J, Schlieper G, Saritas T, Ernst S, Beaujean N, Schaeffner E, Baid-Agrawal S, Theisen K, Haller H, Menne J, Zeier M, Sommerer C, Woitke R, Wolf G, Busch M, Fuß R, Sitter T, Blank C, Wanner C, Börner-Klein A, Bauer B, Raschenberger J, Kollerits B, Schönherr S, Oefner P, Gronwald W, Zacharias H, Schmid M, Nadal J
Journal: Kidney International
Publication year: 2019
ISSN: 0085-2538


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.


FAU Authors / FAU Editors

Bärthlein, Barbara
Lehrstuhl für Medizinische Informatik
Beck, Andreas
Lehrstuhl für Medizinische Informatik
Eckardt, Kai-Uwe Prof. Dr. med.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Meiselbach, Heike
Sonderforschungsbereich 796 (mit integriertem Graduiertenkolleg) Steuerungsmechanismen mikrobieller Effektoren in Wirtszellen
Prokosch, Hans-Ulrich Prof. Dr.
Lehrstuhl für Medizinische Informatik
Schneider, Markus
Medizinische Fakultät


External institutions with authors

Albert-Ludwigs-Universität Freiburg
eurac research
Medizinische Universität Innsbruck
Universitätsklinikum Würzburg


How to cite

APA:
Fazzini, F., Lamina, C., Fendt, L., Schultheiss, U.T., Kotsis, F., Hicks, A.A.,... Nadal, J. (2019). Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease. Kidney International. https://dx.doi.org/10.1016/j.kint.2019.04.021

MLA:
Fazzini, Federica, et al. "Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease." Kidney International (2019).

BibTeX: 

Last updated on 2019-21-07 at 08:02