Mitochondrial DNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients.
BACKGROUND
Oxidative stress is highly prevalent in hemodialysis patients and may contribute to atherosclerosis and mortality. The copy number of mitochondrial DNA (mtDNA) is affected by oxidative stress in blood circulation. This study aimed to test whether mtDNA copy number correlates with oxidative stress and predicts all-cause mortality in nondiabetic hemodialysis patients.


METHODS
Ninety-five nondiabetic hemodialysis patients and 95 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS) and plasma free thiol were used as indicators of oxidative stress and antioxidant defense, respectively. Mitochondrial DNA copy number in peripheral blood leukocytes was measured by determining relative amounts of mtDNA to nuclear DNA by quantitative real-time PCR. All-cause mortality of hemodialysis patient was recorded during a follow-up of 3 years.


RESULTS
Nondiabetic hemodialysis patients showed higher TBARS levels, lower free thiol levels and higher mtDNA copy numbers compared with normal control subjects. The plasma TBARS level was a significant factor correlating positively to the mtDNA copy number (p=0.024). Patients with a mtDNA copy number higher than the median had a higher all-cause mortality than patients with a lower mtDNA copy number (17.0% vs. 4.2%; log-rank test: p=0.038). A 1-log increase in mtDNA copy number was independently related to an increase in the risk for mortality (hazard ratio 21.360; 95% confidence interval, 1.298-351.572).


CONCLUSIONS
Nondiabetic hemodialysis patients had higher oxidative stress and mtDNA copy numbers than healthy subjects. The mtDNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients.
Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien - Taiwan.
Yi-Chun
YC
Wang
Wen-Chin
WC
Lee
Shang-Chih
SC
Liao
Lung-Chih
LC
Lee
Yu-Jen
YJ
Su
Chien-Te
CT
Lee
Jin-Bor
JB
Chen
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011237:Predictive Value of Tests; D006435:Renal Dialysis; D012189:Retrospective Studies; D013438:Sulfhydryl Compounds / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015415:Biomarkers; D004272:DNA, Mitochondrial; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances