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Background: Endotoxemia is common in peritoneal dialysis (PD) patients, and circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We hypothesize that circulating bacterial DNA, another microbial component, correlates with the degree of systemic inflammation and predicts the survival of new PD patients., Methods: We measured the plasma bacterial DNA level in the archive blood samples of 300 consecutive new PD patients. The result was compared with serum C-reactive protein (CRP) level, patient survival and peritonitis-free survival., Results: The average age was 57.8 ± 12.1 years, average plasma bacterial DNA level 34.3 ± 1.3 cycles and average follow-up 37.9 ± 22.2 months. The plasma bacterial DNA level correlated with serum CRP (r = 0.565, P < 0.001) and LPS levels (r = 0.224, P = 0.029). At 36 months, the patient survival were 77.5, 78.3, 74.6 and 65.2% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (log-rank test, P = 0.034). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, the plasma bacterial DNA level had no independent effect. Similarly, peritonitis-free survival were 60.6, 59.8, 60.3 and 50.4% for plasma bacterial DNA level quartiles I, II, III and IV, respectively, at 36 months (P = 0.020), and the difference was not significant after adjusting for confounding factors., Conclusion: We found that the plasma bacterial DNA level correlated with the degree of systemic inflammatory state in PD patients. Although plasma bacterial DNA level seems to predict patient survival and peritonitis-free survival, the association disappears after adjusting for confounding factors. Further prospective studies are needed to delineate the role of plasma bacterial DNA as a prognostic marker of renal failure patients.

Background and Objectives: Both larger molecule removal and dialyzer biocompatibility have been implicated in the high-flux hemodialysis (HD)-associated favorable outcome. In an attempt to delineate the effect of membrane permeability, we performed a randomized, crossover study to compare the inflammatory biomarkers, lipid profile, and aortic pulse wave velocity (PWV) of two dialyzers that are composed of identical membranes but with different flux characteristics., Design, Setting, Participants, & Measurements: Stable patients who had anuria and were on low-flux polysulfone membrane were randomly allocated either to HD with high-flux polyamide membrane (group A; 22 patients) or to HD with low-flux polyamide membrane (group B; 24 patients) for 24 weeks, then they were started on 24 weeks of the alternative HD treatment. Apart from the dialyzer, the dialysis prescription remained unchanged., Results: Nineteen patients from group A and 23 patients from group B completed the study. Predialysis beta(2)-microglobulin levels decreased significantly when using the high-flux polyamide membrane. No difference between membranes was observed for serum albumin, high-sensitivity C-reactive protein, fibrinogen, IL-6, triglycerides, HDL cholesterol, LDL cholesterol, and lipoprotein(a) during the study. A significant increase in aortic PWV, a marker of aortic stiffness, was noted after patients switched from high-flux to low-flux polyamide membranes. Similarly, the rate of change in aortic PWV was significantly decreased with the use of the high-flux polyamide membrane., Conclusions: Our findings suggest that dialysis with polyamide membranes with different flux characteristics did not modify the inflammatory indices and lipid profile in stable HD patients; however, a seemingly beneficial effect on aortic stiffness was noted for patients who were maintained on high-flux polyamide membrane.

Background and Objectives: Systemic inflammatory state is a hallmark of peritoneal dialysis (PD) patients, but its etiology remains obscure. Because circulating microbial products are an important cause of systemic immune activation in other conditions such as HIV infection, it was hypothesized that endotoxemia is a cause of systemic inflammatory state and atherosclerosis in PD patients., Design, Setting, Participants, & Measurements: Plasma lipopolysaccharide (LPS) levels in 30 consecutive new PD patients were measured. The result was compared with serum C-reactive protein (CRP) level, peritoneal transport status, history of pre-existing cardiovascular diseases, and carotid intima media thickness (IMT) by Doppler ultrasound., Results: Among the 30 PD patients, there were 17 men. The average age was 53.7 +/- 15.1 yr. The average endotoxin concentration of PD patients was 0.44 +/- 0.18 EU/ml, which was significantly higher than that of patients with chronic kidney disease secondary to Ig-A nephropathy (IgAN) (0.035 +/- 0.009 EU/ml, P < 0.0001) and the controls (0.013 +/- 0.007 EU/ml, P < 0.0001). In PD patients, plasma LPS concentration had a significant correlation with serum CRP (r = 0.415, P = 0.025) and serum albumin level (r = -0.394, P = 0.034). In contrast, plasma LPS level did not correlate with Charlson's Comorbidity Index, peritoneal transport characteristics, or nutritional indices. Patients with pre-existing cardiovascular disease (CVD) had higher plasma LPS level than those without CVD (0.53 +/- 0.19 versus 0.36 +/- 0.16 EU/ml, P = 0.016). Plasma LPS level correlated with carotid IMT (r = 0.438, P = 0.016)., Conclusions: It was found that endotoxemia was probably common in PD patients, and the degree of circulating endotoxemia might be related to the severity of systemic inflammation and features of atherosclerosis. This result suggests that endotoxemia may have a contributory role to the systemic inflammatory state and accelerated atherosclerosis in PD patients.

Background: Endocan is associated with endothelial dysfunction. In peritoneal dialysis (PD) patients, cardiovascular disease is a common cause of mortality. We examined the relationship between serum endocan level and clinical outcome of PD patients. Methods: We recruited 193 new PD patients (118 males, mean age 58.8 ± 11.6 years). Serum endocan levels were determined and stratified into tertile 1 (lowest) to 3 (highest). Nutritional status, arterial pulse wave velocity (PWV) and serum C-reactive protein (CRP) levels were measured. The patients were followed for at least 4 years for clinical outcomes. Results: For the whole cohort, patients with higher serum endocan levels had lower serum albumin and subjective global assessment score, higher carotid-femoral PWV, and higher serum CRP. For patients with suboptimal blood pressure (BP) control, cardiovascular event-free survival was 95.0, 95.5, and 78.5% for tertiles 1, 2, and 3 at 60 months respectively (p = 0.019). Multivariate Cox regression analysis showed that serum endocan level was an independent predictor of cardiovascular event-free survival. No association with cardiovascular event-free survival was found for patients with adequate BP control (95.0, 92.3, and 100% for tertile 1, 2, and 3 at 60 months, respectively, p = 0.6). Conclusions: Higher serum endocan level is associated with unfavourable nutritional, arterial and inflammatory conditions in PD patients. In patients with suboptimal BP control, higher serum endocan is also associated with worse cardiovascular outcome. [ABSTRACT FROM AUTHOR]

Aim C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP-transgenic (Tg) mice after PD treatment. Methods WT ( n = 7) and CRP-Tg ( n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis. Results After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor α (TNFα) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice. Conclusions CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients. Methods: We studied 347 new PD cases (181 males, age 56.6 ± 13.7 years). Genotyping was done by standard methods. Patients were followed for 40.5 ± 20.7 months for survival analysis. Results: For the entire cohort, there was no difference in the 5-year survival between genotype groups. However, there was a significant interaction between HSP polymorphism and diabetic status on the cardiovascular event-free survival. In patients without pre-existing diabetes, 5-year cardiovascular event-free survival of the GG/AG genotype group was significantly better than that of the AA genotype group (57.2 vs. 32.1%, p = 0.011). Conclusion: The G allele of the HSP70-2 A+1267G polymorphism confers survival advantages in non-diabetic PD patients. The role of HSP in the pathogenesis of cardiovascular disease in renal failure patients needs further investigation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the major cause of mortality and morbidity in dialysis patients. Recently, circulating endotoxin is found to associate with the systemic inflammatory state and cardiovascular disease of dialysis patients. Previous studies showed that the use of ultrapure dialysate for hemodialysis could reduce the exposure to exogenous endotoxin. We studied the effect of using ultrapure dialysate for hemodialysis on circulating endotoxin and bacterial DNA fragment levels and vascular stiffness. Methods: This is an open-labeled prospective study of 25 patients (14 male). Circulating endotoxin and bacterial DNA level, vascular stiffness as represented by arterial pulse wave velocity (PWV), nutrition and hydration status were monitored before and repeatedly throughout 12 months after the use of ultrapure dialysate for hemodialysis. Results: The average age was 58.9 ± 10.2 years; 21 patients completed the study. Within 4 weeks of conversion to ultrapure dialysate for hemodialysis, the plasma endotoxin level fell from 0.302 ± 0.083 to 0.209 ± 0.044 EU/ml (p < 0.0001) and then remained static, while serum bacterial DNA level remained similar. Furthermore, the time-averaged plasma endotoxin level during the study period significantly correlated with serum C-reactive protein level (r = 0.483, p = 0.017), carotid-femoral PWV (r = 0.455, p = 0.033), and malnutrition inflammation score (r = 0.461, p = 0.031). The time-averaged serum bacterial DNA level significantly correlated with malnutrition inflammation score (r = 0.550, p = 0.008) and inversely with subjective global assessment score (r = -0.543, p = 0.009), but not with PWV. Conclusions: In hemodialysis patients, circulating endotoxin level is associated with vascular stiffness and systemic inflammation. Using ultrapure dialysate for hemodialysis effectively reduces circulating endotoxin level in hemodialysis patients. The long-term benefit of using ultrapure dialysate for hemodialysis requires further study. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Myeloid-related protein 8/14 (MRP8/14) is released by cells of myeloid lineage upon inflammatory challenges. Experimental data suggested that MRP8/14 is important in the initiation and progression of inflammation and cardiovascular diseases. We examined the relation between serum MRP8/14 level and cardiovascular disease in Chinese peritoneal dialysis (PD) patients. Methods: We studied 102 new PD patients (58 males, mean age 57.3 ± 11.9 years). Baseline serum MRP8/14 was determined and grouped to quartiles for analysis. All patients were then followed for an average of 23.9 ± 6.9 months. Results: There was a trend of lower 3-year cardiovascular event-free survival for patient quartiles with high serum MRP8/14 levels (log-rank test, p = 0.064). The 3-year actuarial survival was significantly lower for quartile groups with higher MRP8/14 levels (96.0, 94.7, 72.9, and 62.5% for quartiles 1–4, respectively, p = 0.003). Cox regression analysis showed that serum MRP8/14 level and Kt/V were independent predictors of actuarial survival; in this model, every 1 µg/ml increase in serum MRP8/14 level confers a 25.1% increase in risk of death (95% confidence interval, 1.3–54.4%, p = 0.037). There was no significant difference in technique survival between the MRP8/14 quartile groups. Conclusion: A high baseline serum MRP8/14 level was associated with a lower actuarial survival in Chinese PD patients. The pathogenic role of MRP8/14 in the cardiovascular disease of PD patients needs further investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. Methods: We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months. Results: Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months ( P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P = 0.010). Conclusion: A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation. [ABSTRACT FROM AUTHOR]

Summary: Background/Purpose: Human oxoguanine-DNA glycosylase 1 (hOGG1) is the enzyme that has DNA repairing capacity. C1245 G substitution of the hOGG1 gene results in reduced enzyme activity. Peritoneal dialysis (PD) is known to cause oxidative DNA damage. We investigated the effect of hOGG1 polymorphism on the clinical outcomes of PD patients. Methods: We studied the hOGG1 polymorphism in 441 new PD patients (232 men, age 56.6±13.5 years). The patients were followed for 41.4±18.2 months for cardiovascular events. Results: For the entire cohort, there was no significant difference in the 5-year event-free survival between the CC and CG/GG groups (42.9% vs. 33.2%; p =0.1). However, for patients with baseline serum C-reactive protein (CRP) levels ≤ 5.0mg/L, 5-year event-free survival of the CC group was significantly better than that of CG/GG group (50.3% vs. 31.9%, p =0.046). Multivariate analysis showed that hOGG1 polymorphism was an independent predictor of the survival (p =0.008). In contrast, for patients with baseline CRP > 5.0mg/L, there was no significant difference in 5-year event-free survival between the CC and CG/GG groups (26.7% vs. 30.2%, p =0.9). Conclusion: In PD patients with no systemic inflammation, hOGG1 1245CC genotype confers a survival benefit as compared to CG or GG genotype, but the protective effect disappears in patients with systemic inflammation. Our results suggest a complex interaction between hOGG1 and inflammation in the pathogenesis of cardiovascular disease in PD patients. 背景: 人類oxoguanine-DNA glycosylase 1 (hOGG1)是一種具DNA修復能力的酵素，其酵素活動在hOGG1基因的C1245G替換後會有所下降。此外，腹膜透析(PD)已知會導致DNA的氧化性損害。本研究調查了hOGG1多態性對PD患者的影響。 方法: 研究人員對441位剛開始接受PD的病人(男232人, 年齡56.6 ± 13.5歲)，作出hOGG1多態性的調查，並對心血管事件的發生進行共41.4 ± 18.2個月的追蹤。 結果: 在整體病人中，CC與CG/GG組別之間在5年無事件存活率上無明顯差異(42.9% vs. 33.2%, p = 0.1)；然而，在基線血清C-反應蛋白(CRP)水平 ≤ 5.0 mg/L的病人中，CC組的5年無事件存活率明顯高於CG/GG組(50.3% vs. 31.9%, p = 0.046)。多變數分析顯示，hOGG1多態性是存活的獨立預測因子(p = 0.008)。相反，在基線CRP > 5.0 mg/L的病人中， CC與CG/GG組別之間在5年無事件存活率上並無明顯差異(26.7% vs. 30.2%, p = 0.9)。 結論: 在不具系統性發炎的PD患者間，相比於CG或GG基因型，hOGG1 1245CC基因型具備若干的存活效益，但其效益並未出現於系統性發炎患者間。這些結果意味著，在PD患者的心血管致病過程中，hOGG1與發炎之間存在著複雜的交互關係。 [Copyright &y& Elsevier]

Aim: The Malnutrition Inflammation Score (MIS) has been proposed for the assessment of nutritional status in peritoneal dialysis (PD) patients. The MIS and the Subjective Global Assessment (SGA) for serial monitoring of nutritional status in PD patients were compared. Methods: The change in the MIS and SGA overall score of 59 PD patients (28 male) over 12 months was studied. Clinical factors relating to the discrepancy between the two instruments were explored. Results: The average patient age was 55.8 ± 9.7 years. Thirty of the 59 patients (50.8%) had exact agreement in the changed MIS and SGA scores. Cohen's κ score was 0.274, indicating a modest degree of agreement. For the detection of deterioration in nutritional status and using the MIS as the reference measure, the SGA had a sensitivity of 61.9% and specificity of 86.8%; serum ferritin level was substantially higher in the ones whose SGA did not detect a deterioration in nutrition (1464.1 ± 873.3 vs 800.5 ± 561.6 pmol/L, P = 0.046). For the detection of improvement in nutritional status, the SGA had a sensitivity of 45.8% and specificity of 82.9%; patients whose SGA did not detect an improvement in nutrition were dialyzed longer (53.8 ± 35.3 vs 27.6 ± 18.9 months, P = 0.038), had higher total iron binding capacity (TIBC) (45.6 ± 5.5 vs 38.2 ± 8.1 µmol/L, P = 0.015), had higher total Kt/V (2.02 ± 0.36 vs 1.75 ± 0.23, P = 0.048) and higher normalized protein nitrogen appearance (1.16 ± 0.25 vs 0.95 ± 0.23 g/kg per day, P = 0.048). Conclusion: The longitudinal changes in the MIS and SGA score have modest agreement with each other. However, PD patients with a longer duration of dialysis, higher serum ferritin, TIBC, total Kt/V or normalized protein nitrogen appearance tend to have discrepancies between the longitudinal changes in the MIS and SGA overall score. [ABSTRACT FROM AUTHOR]

Background The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. Methods We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. Results Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4 h (D/P4) at baseline (r = 0.377, p = 0.001 and r = 0.237, p = 0.037, respectively) and after one year of PD (r = 0.362, p = 0.014 and r = 0.402, p = 0.007). The change in PD effluent − 21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r = 0.470, p = 0.001 and r = 0.479, p = 0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r = 0.387, p = 0.009) and miR-589 (r = 0.336, p = 0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. Conclusion Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport. [ABSTRACT FROM AUTHOR]