Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease.
Aged
Cardiovascular Diseases
/ blood
Cause of Death
DNA Copy Number Variations
DNA, Mitochondrial
/ blood
Female
Follow-Up Studies
Germany
/ epidemiology
Hospitalization
/ statistics & numerical data
Humans
Infections
/ blood
Kaplan-Meier Estimate
Male
Middle Aged
Mitochondria
/ genetics
Oxidative Stress
/ genetics
Prevalence
Prognosis
Proportional Hazards Models
Prospective Studies
Renal Insufficiency, Chronic
/ blood
Risk Factors
chronic kidney disease
infections
mitochondrial DNA copy number
mortality
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
12
12
2018
revised:
29
03
2019
accepted:
05
04
2019
pubmed:
30
6
2019
medline:
2
10
2020
entrez:
29
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31248648
pii: S0085-2538(19)30483-1
doi: 10.1016/j.kint.2019.04.021
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
480-488Investigateurs
Kai-Uwe Eckardt
(KU)
Heike Meiselbach
(H)
Markus Schneider
(M)
Thomas Dienemann
(T)
Hans-Ulrich Prokosch
(HU)
Barbara Bärthlein
(B)
Andreas Beck
(A)
Thomas Ganslandt
(T)
André Reis
(A)
Arif B Ekici
(AB)
Susanne Avendaño
(S)
Dinah Becker-Grosspitsch
(D)
Ulrike Alberth-Schmidt
(U)
Birgit Hausknecht
(B)
Rita Zitzmann
(R)
Anke Weigel
(A)
Gerd Walz
(G)
Anna Köttgen
(A)
Ulla Schultheiß
(U)
Fruzsina Kotsis
(F)
Simone Meder
(S)
Erna Mitsch
(E)
Ursula Reinhard
(U)
Jürgen Floege
(J)
Georg Schlieper
(G)
Turgay Saritas
(T)
Sabine Ernst
(S)
Nicole Beaujean
(N)
Elke Schaeffner
(E)
Seema Baid-Agrawal
(S)
Kerstin Theisen
(K)
Hermann Haller
(H)
Jan Menne
(J)
Martin Zeier
(M)
Claudia Sommerer
(C)
Rebecca Woitke
(R)
Gunter Wolf
(G)
Martin Busch
(M)
Rainer Fuß
(R)
Thomas Sitter
(T)
Claudia Blank
(C)
Christoph Wanner
(C)
Vera Krane
(V)
Antje Börner-Klein
(A)
Britta Bauer
(B)
Florian Kronenberg
(F)
Julia Raschenberger
(J)
Barbara Kollerits
(B)
Lukas Forer
(L)
Sebastian Schönherr
(S)
Hansi Weissensteiner
(H)
Peter Oefner
(P)
Wolfram Gronwald
(W)
Helena Zacharias
(H)
Matthias Schmid
(M)
Jennifer Nadal
(J)
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.