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

<div><p>Background</p><p>Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients.</p><p>Methods</p><p>We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival.</p><p>Results</p><p>The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005).</p><p>Conclusions</p><p>Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients.</p></div

Baseline biochemical data and dialysis prescription.

<p>HDL, high density lipoprotein; LDL, low density lipoprotein; D/P, dialysate-to-plasma concentration ratio of creatinine; MTAC, mass transfer area coefficient; GFR, glomerular filtration rate; NPNA, normalized protein nitrogen appearance; FEBM, fat-free edema-free body mass by creatinine kinetics. Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Data are compared by one way analysis of variance (ANOVA).</p><p>Baseline biochemical data and dialysis prescription.</p

Kaplan-Meier plot of (A) event-free survival; and (B) cardiovascular disease-free survival (excluding congestive heart failure).

<p>Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Data are compared by the log rank test.</p

Baseline demographic and clinical data.

<p>PD, peritoneal dialysis; PCR, polymerase chain reaction. Patients were divided to quartiles of plasma bacterial DNA. Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. Note that a higher PCR cycle number indicates a lower level of bacterial DNA. Data are compared by Chi square test or one way analysis of variance (ANOVA) as appropriate.</p><p>Baseline demographic and clinical data.</p

Comparison of (A) number of hospital admission; and (B) duration of hospitalization between quartiles of plasma bacterial DNA level.

<p>Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. (p < 0.0001 by Kruskal Wallis test for all comparisons between quartiles) (White box, hospitalization for all cause; hatched box, hospitalization for cardiovascular reasons.)</p

Comparison of (A) carotid-radial; and (B) carotid-femoral pulse wave velocity (PWV) between quartiles of plasma bacterial DNA level.

<p>Quartile I had the lowest while quartile IV the highest plasma bacterial DNA level. P values depicted are computed by paired Student’s t test.</p

Independent predictors of hospitalization for cardiovascular reasons by log-linear model.

<p>CI, confidence interval; MIS, malnutrition inflammation score.</p><p>NB. e^COEF was the exponential coefficient indicating the relative number of hospital admission (per year) or duration of hospitalization (days per year of follow up) compared to the 2-fold lower of plasma bacterial DNA level (i.e. one extra threshold cycle of polymerase chain reaction), and 1 point less for MIS.</p><p>Independent predictors of hospitalization for cardiovascular reasons by log-linear model.</p

Cox proportional hazards model of composite cardiovascular end-point.

<p>AHR, adjusted hazard ratio; CI, confidence interval; MIS, malnutrition inflammation score; GFR, glomerular filtration rate.</p><p>Cox proportional hazards model of composite cardiovascular end-point.</p