Fazzini, Federica and Lamina, Claudia and Fendt, Liane and Schultheiss, Ulla T. and Kotsis, Fruzsina and Hicks, Andrew A. and Meiselbach, Heike and Weissensteiner, Hansi and Forer, Lukas and Krane, Vera and Eckardt, Kai-Uwe and Koettgen, Anna and Kronenberg, Florian and Schneider, Markus and Dienemann, Thomas and Prokosch, Hans-Ulrich and Barthlein, Barbara and Beck, Andreas and Ganslandt, Thomas and Reis, Andre and Ekici, Arif B. and Avendano, Susanne and Becker-Grosspitsch, Dinah and Alberth-Schmidt, Ulrike and Hausknecht, Birgit and Zitzmann, Rita and Weigel, Anke and Walz, Gerd and Schultheiss, Ulla and Kotsis, Fruzsina and Meder, Simone and Mitsch, Erna and Reinhard, Ursula and Floege, Jurgen and Schlieper, Georg and Saritas, Turgay and Ernst, Sabine and Beaujean, Nicole and Schaeffner, Elke and Baid-Agrawal, Seema and Theisen, Kerstin and Haller, Hermann and Menne, Jan and Zeier, Martin and Sommerer, Claudia and Woitke, Rebecca and Wolf, Gunter and Busch, Martin and Fuss, Rainer and Sitter, Thomas and Blank, Claudia and Wanner, Christoph and Krane, Vera and Borner-Klein, Antje and Bauer, Britta and Raschenberger, Julia and Kollerits, Barbara and Forer, Lukas and Schonherr, Sebastian and Weissensteiner, Hansi and Oefner, Peter and Gronwald, Wolfram and Zacharias, Helena and Schmid, Matthias and Nadal, Jennifer (2019) Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease. KIDNEY INTERNATIONAL, 96 (2). pp. 480-488. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERIPHERAL-BLOOD; MECHANISMS; STRESS; RISK; QUANTIFICATION; DYSFUNCTION; MODERATE; FISSION; HEALTH; TARGET; chronic kidney disease; infections; mitochondrial DNA copy number; mortality |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 08:53 |
| Last Modified: | 01 Apr 2020 08:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26568 |
Actions (login required)
 |
View Item |
