Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

Szeto, Cheuk‐Chun; Kwan, Bonnie Ching‐Ha; Chow, Kai‐Ming; Kwok, Jeffrey Sung-Shing; Lai, Ka-Bik; Cheng, Phyllis Mei-Shan; Pang, Wing‐Fai; Ng, Jack Kit‐Chung; Chan, Michael; Lit, Lydia C.W.; Leung, Chi‐Bon; Li, Philip Kam-Tao

doi:10.1371/journal.pone.0125162

Cited by 32 publications

(35 citation statements)

References 41 publications

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“…It should be noted, however, that our local policy mandates hospital admission for many intervention procedures, such as cardiac catheterization and colonoscopy. Unfortunately, we do not have the detailed breakdown on the cause of hospitalization for our patients, but the gure in this study is similar to our previous reports [29,30].…”

Section: Discussionsupporting

confidence: 80%

Depression Does Not Predict Clinical Outcome of Chinese Peritoneal Dialysis Patients After Adjusting for the Degree of Frailty

CHAN

NG²,

Chow³

et al. 2020

Preprint

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Abstract Background Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients. Methods In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality. Results Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9%, 86.5%, 82.4% and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011-2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score. Conclusion Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.

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Section: Discussionsupporting

confidence: 80%

Depression Does Not Predict Clinical Outcome of Chinese Peritoneal Dialysis Patients After Adjusting for the Degree of Frailty

CHAN

NG²,

Chow³

et al. 2020

Preprint

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“…Based on our studies, both plasma mitochondrial and bacterial DNA levels correlate with serum CRP level and predict cardiovascular events [14,17], but the plasma levels of the two DNA species have no internal correlation (our unpublished data). It could be argued that since the PCR cycle number of plasma mitochondrial DNA level is generally around 15 lower than bacterial DNA level, the absolute level of the former is at least 1000-fold higher than the latter.…”

Section: Discussionmentioning

confidence: 82%

“…Mitochondrial DNA is structurally similar to bacterial DNA and contains unmethylated CpG motifs that binds to toll-like receptor-9 (TLR-9) [18][19][20][21][22], which results in downstream activation of an inflammatory cascade and potentially acute cardiac damage [27,28]. Our previous studies showed that plasma level of bacterial DNA fragment, which activates the same TLR-9 pathway, correlates with the severity of systemic inflammation and is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients [14,17]. Taken together, these studies suggest that both endogenous (mitochondrial) and exogenous (bacterial) DNA fragments are important uremic toxins that contribute to the pathogenesis of systemic inflammation and cardiovascular disease in PD and probably CKD patients.…”

Section: Discussionmentioning

confidence: 99%

“…There is emerging evidence that bacterial fragments are present in the circulation of CKD patients and contributes to the sytemic inflammatory state [13,14]. For example, plasma endotoxin level correlates with the degreee of systemic inflammation and carotid intimal thickness in peritoneal dialysis (PD) patients [15,16], while plasma bacterial DNA fragment level is a strong predictor of cardiovascular event and hospitalization [17].…”

Section: Introductionmentioning

confidence: 99%

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Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients

Szeto

Lai²,

Chow³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients.

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“…68 In another study on patients on PD, plasma endotoxin level correlated with the number of hospital admission and duration of hospitalization for cardiovascular reasons. 69 In patients on hemodialysis, a cohort study found that plasma endotoxin level had a modest but significant correlation with serum CRP level and is an independent predictor of patient death within 3 years. 70 In another study, plasma endotoxin level significantly correlated with serum soluble CD14 level, which is associated with inflammation and protein-energy wasting.…”

Section: Pathogenic Mechanismsmentioning

confidence: 99%

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

Szeto

McIntyre

2018

JASN

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Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.

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Circulating Bacterial-Derived DNA Fragment Level Is a Strong Predictor of Cardiovascular Disease in Peritoneal Dialysis Patients

Cited by 32 publications

References 41 publications

Depression Does Not Predict Clinical Outcome of Chinese Peritoneal Dialysis Patients After Adjusting for the Degree of Frailty

Depression Does Not Predict Clinical Outcome of Chinese Peritoneal Dialysis Patients After Adjusting for the Degree of Frailty

Plasma Mitochondrial DNA Level is a Prognostic Marker in Peritoneal Dialysis Patients

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

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