| BackgroundCardiovascular disease (CVD) is the leading cause of death in patients with ESRD undergoing dialysis. Risk factors for CVD in these patients include those that affect the general population, such as diabetes, hypertension, and those related to ESRD as well as those that are specific to chronic dialysis, such as volume load, chronic inflammation state, oxidative state. It remains of paramount importance to distinguish the contributions of these factors to cardiovascular morbidity and mortality in patients undergoing maintenance dialysis. The non-traditional risk factors for CVD such as oxidative stress have been attracted increasing attention in the setting of chronic renal failure.Oxidative stress is defined as the tissue damage resulting from an imbalance between an excessive generation of oxidant compounds and insufficient anti-oxidant defense mechanisms. Advanced oxidation protein products (AOPPs) are the dityrosine-containing and cross-linking protein products formed during oxidative stress by reaction of plasma protein with chlorinated oxidants Its concentration closely correlates with the level of dityrosine, a hallmark of oxidized protein. Therefore, AOPPs have been considered as the markers of oxidant-mediated protein damage. Some study revealed a close relationship between AOPPs levels and serum markers of oxidative stress under the condition of chronic kidney disease. In addition, AOPPs are involved in vascular endothelial cell dysfunctions. Plasma AOPPs level associated with carotid artery intima-media thickness in patients on hemodialysis (HD). There is a close relationship between Plasma AOPPs level and atheroslerosis severity in patients on atherosclerotic. Plasma AOPPs accumulation is positively associated with atheroslerosis in patients with CKD. the serum level of AOPPs is higher in type2diabetic patients with microvascular complications than that none. Therefore, AOPPs are considered to play a role in the development of CVD in patients with end-stage renal disease (ESRD).Objective:Compared the serum levels of AOPPs in patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) and evaluated its clinical relevance.Methods1, Study populationA total of2,095patients were recruited from the9of the provincial dialysis centers in China (at least200HD patients or100CAPD patients in each center) from march,2010to march,2011. The minimal dialysis duration was3months and patients with18to80years old are enrolled. Patients that have congential heart disease or valvular heart disease are excluded. Appropriate approval was obtained from the local ethics committee.2, Dialysis regimensPatients maintained on HD were dialyzed twice or thrice weekly with low-flux polysulphone or polyacrylamide dialyzer, either1.5or1.7m2. All treatments were of4-hour to5-hour duration with conventional glucose-free, bicarbonate-based dialysate containing1.25mM-1.5mM calcium,2.0mM potassium, and138mM sodium. Dialysate flow was500ml/min. All CAPD patients used1.25%to4.25%glucose-containing solutions (Baxter) as prescribed for routine clinical care.3, Definition of CVDCardiovascular morbidity was defined as the presence of clinically diagnosed ischemic heart disease, heart failure, peripheral vascular disease, and/or stroke as described previously. Ischemic heart disease was defined as the presence of myocardial infarction, angina, and ischemia on electrocardiogram or other diagnostic tests. The diagnosis of heart failure was based on an ejection fraction below40%or New York Heart Association Criteria grade3or more. Peripheral vascular disease was defined as the presence of amputation of digits or extremities secondary to vascular disease, intermittent claudication, or toe gangrenes secondary to vascular disease.4, Data collectionDemographic characteristic, cardiovascular disease, drug treatment, hematology and biochemistry results were recorded.. Blood test was performed by the clinical laboratories in individual dialysis centers. The serum samples of MDA and AOPPswere collected.5, statistic analysisStatistical analyses were performed with SPSS13.0for Windows(?). Descriptive statistics that used means, medians, proportions, SE, and confidence intervals were performed on all variables where appropriate. The continuous data were presented as the mean±tandard deviation or the median and interquartile ranges where appropriate. Categorical variables are presented as percentages. The Pearson χ2test and the Kruskal-Wallis test were applied for analysis of nominal and ordinal variables, respectively. Bivariate correlations between study variables were calculated by Spearman rank coefficients. Multivariate linear regression was performed to identify independent determinants of AOPPs. The odds ratios describing the association of selected risk factors with ischemic heart disease (IHD) were obtained by the univariable and multivariable logistic regression analysis, respectively. A P value of <0.05(2-sided) was considered significant for statistical testing.Result(1) Characteristics of the Study CohortIn this cohort,1160(55.4%) were male. The mean age was54years old. The median time for dialysis was26months (12-49months). The mean of body mass index (BMI) was21.6kg/m2. Most of patients (85%) had hypertension. Diabetes affected23.1%patients. In the control group,148(55.2%) were male. The mean age was53.7years old. The serum levels of AOPPs were significantly increased in patients on maintenance dialysis (median:74.4;25th-75th percentile:63.8-87.4μmol/L) compared with that in age-matched healthy control (median:51.80;25th-75th percentile:46.10-58.70μmol/L).The serum level of AOPPs was significantly higher in HD patients in comparison to CAPD patients. Compared with HD patients, CAPD patients were younger with shorter dialysis vintage. In addition, hypertension, elevated BMI, as well as increased serum triglyceride and cholesterol were more prevalent in CAPD patients. Meanwhile, the serum level of ferritin and dose of iron used were higher in HD patients.(2) Factors associated with AOPPs accumulationTo identify the factors which are associated with AOPPs accumulation in this cohort, we performed the spearman rank correlation analysis. The levels of AOPPs in total patients were significantly correlated with age(r=0.119, P<0.001). BMI(r=0.088, P<0.01), dialysis vantage(r=0.I02, P<0.05), and diabetes(r=0.081, P<0.01), as well as serum level of triglyceride(r=0.242, P<0.01) and cholesterol(r=0.072, P<0.05). Additionally, AOPPs accumulation was closely associated with the serum level of ferritin(r=0.100, P<0.01) and MDA(r=0.219, P<0.01). It was interesting to note that accumulation of AOPPs was correlated with IHD but not the other cardiovascular diseases such as heart failure, stroke, and peripheral vascular disease.Since serum levels of AOPPs were higher in HD compared with CAPD patients, we also performed bivariate correlations in HD and CAPD, separately. The association between AOPPs accumulation and IHD could be found only in HD patients. Multivariate linear analysis still showed that The association between AOPPs accumulation and IHD could be found only in HD patients(3) Correlation of AOPPs with IHDAmong the patients on HD, the proportion of patients with IHD was significantly higher in patients with AOPPs levels equal and above the median (75.2umol/L)(24.9%,193/775) compare to that of patients with AOPPs levels below the median (17.1%,131/766, p<0.01).Since the AOPPs concentration can be interfered in the presence of elevated triglyceride, we further analyzed the relationship of AOPPs accumulation with the presence of IHD in HD patients stratified by the levels of triglyceride, namely normal(TG≤1.70mM) and high(TG>1.70mM)group.As shown, patients with higher levels of AOPPs (≥median) presented significantly more prevalent IHD in patients with both normal and high triglyceride, suggesting that the relationship of AOPPs with IHD might not attribute to high triglyceride.Since progression of IHD is a time-dependent process, we analyzed the correlation of IHD with AOPPs in HD patients stratified by dialysis vintage, namely groupl(3-24mo), group2(25-60mo), group3(61-252mo). As shown, accumulation of AOPPs was associated with increased prevalence of IHD in each category of dialysis vintage, suggesting that the relationship of AOPPs with IHD might not attribute to dialysis vintage.Since chronic inflammation state is closely associated with development of IHD in HD patients. We analyzed the correlation of IHD with AOPPs in HD patients stratified by the level of C-reactive protein, namely low(≤10mg/1) and high(>10mg/l) group. As shown, patients with higher levels of AOPPs (≥median) presented significantly more prevalent IHD in patients with both low and high C-reactive protein, suggesting that the relationship of AOPPs with IHD might not attribute to C-reactive protein.(4) Factors associated with IHDTo determine the independent effects of serum levels of AOPPs and other risk factors on IHD in HD patients, we performed univariate logistic regression analysis using IHD as the dependent variable. As shown, old age (≥50Years), hypertension, diabetes, increased C-reactive protein (>10mg/1), triglyceride (>1.70mmol/l) and cholesterol (>6.99mmol/l), decreased albumin (<40g/l) and accumulation of MDA, AOPP were identified as the independent risk factors for development of IHD in HD patients. Multivariate regression analysis showed that accumulation of AOPPs was still an independent risk factor for IHD after adjustment of other risk factors.ConclusionThe serum level of AOPPs was significantly higher in HD patients in comparison to CAPD patients. The level of AOPPs was independently associated with IHD only in HD patients. |
PDF Full Text Request