Oxidative Dna Damage and Mortality in Hemodialysis and Peritoneal Dialysis Patients

Xu, Hong; Watanabe, Makoto; Qureshi, Abdul Rashid; Heimbürger, Olof; Bárány, Peter; Anderstam, Björn; Eriksson, Monica; Stenvinkel, Peter; Lindholm, Bengt

doi:10.3747/pdi.2013.00259

Cited by 42 publications

(46 citation statements)

References 41 publications

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“…We also used an ELISA to assess 8‐oxo‐2′‐dG in plasma samples, as conventional chromatographic methods do not have the sensitivity to measure plasma levels. Although the circulating levels of 8‐oxo‐2′‐dG detailed in this study are similar to those reported in cross‐sectional studies using ELISA‐based assays in patients with diabetes mellitus25, 26, 27 and other settings,28, 29, 30, 31, 32 it is understood that ELISA overestimates 8‐oxo‐2′‐dG when compared with high‐sensitivity mass spectroscopy 33. This is partly because of the former method including DNA fragments containing 8‐oxo‐2′‐dG, in addition to free 8‐oxo‐2′‐dG, as well as the presence of interfering compounds in plasma.…”

Section: Discussionsupporting

confidence: 82%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

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Background8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐2′‐dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8‐oxo‐2′‐dG and major cardiovascular outcomes in diabetes mellitus is weak.Methods and ResultsA case‐cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (http://ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow‐up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8‐oxo‐2′‐dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1‐SD increase in plasma 8‐oxo‐2′‐dG was 1.10 (95% confidence interval, 1.01–1.20; P=0.03). This was driven by an independent association between plasma 8‐oxo‐2′‐dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10–1.37 [P<0.001]). By contrast, no association was seen between 8‐oxo‐2′‐dG and noncardiovascular disease death (of which cancer was the major single cause). 8‐Oxo‐2′‐dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke.ConclusionsIn adults with type 2 diabetes mellitus, increased levels of 8‐oxo‐2′‐dG are independently associated with all‐cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

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Section: Discussionsupporting

confidence: 82%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

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“…Several studies reported the strong association between serum ADMA levels and mortality, as well as CV events in stable HD patients . OS‐mediated DNA damage has also been associated with enhanced atherosclerosis, all‐cause and CV mortality in maintenance HD patients …”

Section: Os and Clinical Endpointsmentioning

confidence: 99%

“…[81][82][83] OS-mediated DNA damage has also been associated with enhanced atherosclerosis, allcause and CV mortality in maintenance HD patients. 84,85 Another study showed that serum levels of ox-LDL antibodies was a strong independent risk predictor of CV mortality in a cohort of 94 stable, HD patients, followed for 4 years. 86 In a cross-sectional, observational, prospective study, 44 HD patients were followed for a long period (9 years) for all-cause and CV mortality.…”

Section: Os and Clinical Endpointsmentioning

confidence: 99%

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Liakopoulos

Roumeliotis

Zarogiannis

et al. 2018

Seminars in Dialysis

103

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Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS‐mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.

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“…Recently, Xu et al. used multivariable Cox regression models, including 303 hemodialysis and peritoneal dialysis patients adjusted for age, sex, body mass index, dialysis modality, dialysis vintage, and comorbidity score, and found that 8‐hydroxy‐2′‐deoxyguanosine was significantly associated with all‐cause mortality.…”

Section: Oxidative Stress and Outcomementioning

confidence: 99%

“…Nine clinical studies have assessed the relationship between biomarkers of oxidative stress and CVD events, CVD-related mortality, and all-cause mortality in chronic hemodialysis patients (46,(52)(53)(54)(55)(56)(57)(58)(59). Four studies have assessed and demonstrated an association between biomarkers of oxidative stress and the development of new CDV events (51,57,58).…”

Section: Oxidative Stress and Outcomementioning

confidence: 99%

Wishful Thinking: The Surprisingly Sparse Evidence for a Relationship between Oxidative Stress and Cardiovascular Disease in Hemodialysis Patients

Bossola

Tazza

2015

Seminars in Dialysis

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The increased frequency of cardiovascular disease observed in hemodialysis patients is secondary to the combination of many traditional (age, male sex, hypertension, smoking, diabetes mellitus, and dyslipidemia) and novel and uremia-related (inflammation, uremic toxins, adipokine imbalance, coagulation disorders, protein-energy wasting, volume overload, endothelial dysfunction, hyperparathyroidism, and subclinical hypothyroidism) risk factors. Usually, in the latter group, oxidative stress is included. However, after decades of research, it remains essentially unknown if oxidative stress has a causative role in the development of cardiovascular disease in long-term hemodialysis patients because adequate longitudinal studies are lacking. Data deriving from cross-sectional studies suggest that biomarkers of oxidative stress are associated with cardiovascular disease prevalence. Conversely, conflicting and inconclusive results have been obtained on the association between oxidative stress and coronary artery calcification, atherosclerosis, and all-cause and cardiovascular disease-related outcome. It is desirable that further studies are conducted on this topic in the near future.

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Oxidative Dna Damage and Mortality in Hemodialysis and Peritoneal Dialysis Patients

Cited by 42 publications

References 41 publications

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions

Wishful Thinking: The Surprisingly Sparse Evidence for a Relationship between Oxidative Stress and Cardiovascular Disease in Hemodialysis Patients

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