Disease In Peritoneal Dialysis Patients Research Articles

Association of serum thymosin β4 with malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study

Background Malnutrition-inflammation-atherosclerosis (MIA) syndrome may worsen the prognosis of peritoneal dialysis (PD) patients. Serum thymosin β4 (sTβ4) protects against inflammation, fibrosis and cardiac dysfunction. Objectives The present study aimed to characterize the association between sTβ4 and MIA syndrome as well as to investigate the potential of regulating sTβ4 to improve the prognosis of PD patients. Methods We performed a cross-sectional, single-center pilot study involving 76 PD patients. Demographic characteristics, clinical characteristics, nutritional profiles, inflammatory mediators, atherosclerosis-related factors and sTβ4 levels were collected and subjected to association analysis for sTβ4 and MIA syndrome. Results sTβ4 levels did not significantly vary with sex or primary disease in PD patients. Ages and PD features did not vary between patients with different levels of sTβ4. PD patients with higher levels of sTβ4 had significantly higher levels of nutritional indicators, including subjective global nutritional assessment (SGA) (p < 0.001) and serum albumin (ALB) (p < 0.001) but lower levels of inflammatory and atherosclerotic indicators, including serum C reaction protein (CRP) (p = 0.009), the right common carotid artery (RCCA) intimal thickness (p < 0.001) and the left common carotid artery (LCCA) intimal thickness (p = 0.02). Correlation analysis showed that sTβ4 was positively associated with SGA (p < 0.001) and serum ALB (p < 0.001) but negatively associated with CRP (p = 0.020), RCCA intimal thickness (p < 0.001) and LCCA intimal thickness (p = 0.033). In multiple adjusted models, the prevalence of MIA syndrome was significantly decreased in PD patients with increased levels of sTβ4 when patients without MIA syndrome were compared to those with all indicators of MIA syndrome (OR = 0.996, 95% CI 0.993–0.999, p = 0.003) or those with at least one indicator of MIA syndrome (OR = 0.997, 95% CI 0.995–0.998, p < 0.001). Conclusions The sTβ4 level decreases in PD patients with MIA syndrome. The prevalence of MIA syndrome decreases significantly as the level of sTβ4 increases in PD patients.

Predictors of cardiovascular disease in peritoneal dialysis patients: A Prospective longitudinal cohort study

The present study aimed to investigate the incidence rate and possible predictors of cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD).&#x0D; Methods. This prospective longitudinal cohort study included 133 ESRD patients treated with CAPD between 2012 and 2019. The study was conducted in two phases. In the first phase, key patient demographic, clinical, and laboratory data, including the incidence of cardiovascular disease, were collected at baseline. In the second phase, an assessment of potential predictors of CVD in PD patients was performed.&#x0D; Baseline patient characteristics were used as potential predictors in this study. The mean duration of the prospective study was 28.2 ± 7.1 months, corresponding to 249.2 patient-years. Univariate and multivariate Cox proportional hazard regression and ROC analysis were performed to estimate predictors of CVD events. The primary end-point (newly diagnosed cardiovascular disease) was determined at the end of the study. Statistical processing of the results obtained was performed with "MedCalc," version 19.3 (Ostend, Belgium).&#x0D; Results. One hundred and three PD patients were included in the final analysis. During the study period, a significant increase (by 82%) in the frequency of all CVDs was observed (р &lt; 0.0001), more than twice as frequent in heart failure (HF) (р &lt; 0.0001) and atrial fibrillation (AF) (р= 0.0156). The primary endpoint was observed in 49 events: newly diagnosed HF in 21 (20.4%) patients, coronary artery disease in 9 (8.7%) patients, AF in 7 (6.8%) patients, acute myocardial infarction in 5 (4.9%) patients, another coronary heart disease in 7 (6.8%) patients. The incidence rate of CVD and HF was 19.66 and 8.43 per 100 patient-years, respectively. Multivariate Cox regression analysis indicated that hyperhydration (HR=4.2; 95% CI: 2,.2 - 7.3), diabetes mellitus as the primary cause of ESRD (HR=2.5; 95% CI: 1.3 - 4.3), history of MRSA colonization (HR=1.4; 95% CI: 1.2 - 1.7) and age (HR=1.03; 95% CI: 1.004 - 1.05) are independent predictors of all new-onset cardiovascular events in ESRD patients, treated with CAPD.&#x0D; ​A total of 44 patients (42.7%) died during the study period. The incidence rates of all-cause mortality were 17.67 per 100 patient-years. The most common cause of mortality was CVD, accounting for 50.0% of all events (8.82 per 100 patient-years). Conclusions. This prospective longitudinal study demonstrates that treatment with PD is associated with an increased incidence of CVD. Hyperhydration, diabetes mellitus, history of MRSA colonization, and age over 55 years are independent predictors of new-onset CVD in PD patients.

Decrease serum anti-oxLDL antibody is an independent marker of peripheral arterial disease in peritoneal dialysis patients

Background and Aims : Autoantibodies to oxidized low-density lipoprotein (oxLDL) has an inverse associated with carotid artery atherosclerosis and predict development of future cardiovascular disease. Peripheral arterial disease (PAD), defined by low ankle-brachial index (ABI), is associated with increased mortality in patients with chronic renal failure. The present study aimed to determine the relationship between serum anti-oxLDL antibody level and PAD in peritoneal dialysis (PD) patients.Methods: The present cross-sectional, single-center study included 90 PD patients. Serum IgG anti-oxLDL antibody levels were measured using a commercial enzyme immunoassay. ABI values were measured using an automated oscillometric device. Patients with ABIs of <0.9 were categorized into the low ABI group.Results: In the study, 23 of the 90 patients (25.6%) had low ABIs. The rates of diabetes mellitus (P = 0.010) as well as the older age (P = 0.006), serum levels of triglyceride (P = 0.008), fasting glucose (P < 0.001), and C-reactive protein (P < 0.001) were higher, while serum levels of anti-oxLDL antibody (P = 0.008) were lower in the low ABI group compared with the normal ABI group. The multivariable logistic regression analysis revealed that serum levels of anti-oxLDL antibody (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.958–1.000, P = 0.046) and C-reactive protein (each 0.1 mg/dL increase, OR: 1.662, 95% CI: 1.151–2.398, P = 0.007) were independently associated with PAD in PD patients.Conclusions: Serum anti-oxLDL antibody level is negatively associated and C-reactive protein is positively associated with PAD in PD patients. Background and Aims : Autoantibodies to oxidized low-density lipoprotein (oxLDL) has an inverse associated with carotid artery atherosclerosis and predict development of future cardiovascular disease. Peripheral arterial disease (PAD), defined by low ankle-brachial index (ABI), is associated with increased mortality in patients with chronic renal failure. The present study aimed to determine the relationship between serum anti-oxLDL antibody level and PAD in peritoneal dialysis (PD) patients. Methods: The present cross-sectional, single-center study included 90 PD patients. Serum IgG anti-oxLDL antibody levels were measured using a commercial enzyme immunoassay. ABI values were measured using an automated oscillometric device. Patients with ABIs of <0.9 were categorized into the low ABI group. Results: In the study, 23 of the 90 patients (25.6%) had low ABIs. The rates of diabetes mellitus (P = 0.010) as well as the older age (P = 0.006), serum levels of triglyceride (P = 0.008), fasting glucose (P < 0.001), and C-reactive protein (P < 0.001) were higher, while serum levels of anti-oxLDL antibody (P = 0.008) were lower in the low ABI group compared with the normal ABI group. The multivariable logistic regression analysis revealed that serum levels of anti-oxLDL antibody (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.958–1.000, P = 0.046) and C-reactive protein (each 0.1 mg/dL increase, OR: 1.662, 95% CI: 1.151–2.398, P = 0.007) were independently associated with PAD in PD patients. Conclusions: Serum anti-oxLDL antibody level is negatively associated and C-reactive protein is positively associated with PAD in PD patients.

Obesity, Weight Gain, and Fluid Overload in Peritoneal Dialysis.

Obesity is a global epidemic that has a complicated pathogenesis as well as impact on the outcome of peritoneal dialysis (PD) patients. In this review, the prevalence of obesity in incident PD patients as well as the phenomenon of new-onset glucose intolerance after PD will be reviewed. Published literature on the effect of obesity on the survival and incidence of cardiovascular disease in PD patients will be discussed. Particular emphasis would be put on literature that compared the impact of obesity on the outcome of hemodialysis and PD, and the confounding effect of dialysis adequacy. Next, the complex concept of obesity and its relevance for PD will be explored. The focus would be put on the methods of assessment and clinical relevance of central versus general obesity, as well as visceral versus subcutaneous adipose tissue. The relation between obesity and systemic inflammation, as well as the biological role of several selected adipokines will be reviewed. The confounding effects of metabolic syndrome and insulin resistance will be discussed, followed by the prevalence and prognostic impact of weight gain during the first few years of PD. The differences between weight gain due to fluid overload and accumulation of adipose tissue will be discussed, followed by the current literature on the change in body composition after patients are put on chronic PD. The methods of body composition will be reviewed, and the clinical relevance of individual body component (fluid, fat, muscle, and bone) will be discussed. The review will conclude by highlighting current gaps of knowledge and further research directions in this area.

Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress.

One of the main limitations to successful long-term use of peritoneal dialysis (PD) as a renal replacement therapy is the harmful effects of PD solutions to the structure and function of the peritoneal membrane (PM). In PD, the PM serves as a semipermeable membrane that, due to exposure to PD solutions, undergoes structural alterations, including peritoneal fibrosis, vasculopathy, and neoangiogenesis. In recent decades, oxidative stress (OS) has emerged as a novel risk factor for mortality and cardiovascular disease in PD patients. Moreover, it has become evident that OS plays a pivotal role in the pathogenesis and development of the chronic, progressive injury of the PM. In this review, we aimed to present several aspects of OS in PD patients, including the pathophysiologic effects on the PM, clinical implications, and possible therapeutic antioxidant strategies that might protect the integrity of PM during PD therapy.

Effects of soy isoflavones on serum lipids and lipoprotein (a) in peritoneal dialysis patients

Background and aimLipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. Methods & resultsIn this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. ConclusionsThis study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. ClinicalTrials.govNCT03773029. Registration number and dateNCT03773029 - 2018.

High Serum Adipocyte Fatty Acid-Binding Protein Is Associated With Peripheral Artery Disease in Peritoneal Dialysis Patients

BACKGROUND: Peripheral arterial disease (PAD) is a vascular disorder wherein peripheral ischemia is caused by arterial obstruction and results in increased events of cardiovascular disease (CVD). Peritoneal dialysis (PD) is an independent predictor of subclinical PAD and the subsequent mortality in patients with end-stage renal disease. Adipocyte fatty acid-binding protein (A-FABP) is a potential biomarker for CVD risk, especially in patients with overt atherosclerosis. This study was conducted to determine the relationship between PAD and fasting serum levels of A-FABP in patients undergoing PD. METHODS: Fasting blood samples were obtained from 66 PD patients. A-FABP levels were measured using a commercially available enzyme immunoassay kit. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. Serum left or right ABI values of ＜ 0.9 were included in the low ABI group. RESULTS: There were 14 patients (21.2%) in the low ABI group. Compared with patients in the control group, those in the low ABI group had a higher prevalence of diabetes (P = 0.045) and higher serum C-reactive protein (P ＜ 0.001) and A-FABP (P ＜ 0.001) levels but lower weekly Kt/V (P = 0.014) and lower normalized protein equivalent of nitrogen appearance (P = 0.034) values. Multivariate logistic regression analysis of the factors that were significantly associated with PAD revealed that A-FABP (odds ratio, 1.038; 95% confidence interval [CI], 1.004-1.074; P = 0.030) was an independent predictor of PAD in PD patients. The area under the curve plotted to estimate the optimal level of A-FABP predicting PAD in PD patients by the receiver operating characteristic curve analysis was 0.757 (95% CI, 0.636-0.854; P = 0.0004). CONCLUSION: This study demonstrated that a higher serum A-FABP level is an independent predictor of PAD in patients undergoing PD.

Low Serum Levels of Vitamin D are Associated with Progression of Subclinical Atherosclerotic Vascular Disease in Peritoneal Dialysis Patients: A Prospective, Multicenter Study

Background: The prevalence of subclinical atherosclerosis and the main predictors of progression of this condition in patients undergoing peritoneal dialysis (PD) have been insufficiently investigated. Objectives and Method: Following a prospective, multicenter, observational design, we studied 237 patients who were treated with PD for ≥3 months, without any clinical background of cardiovascular (CV) disease. Our objectives were the following: (1) to investigate the prevalence of subclinical atherosclerosis, as compared to a control group of age- and sex-matched healthy individuals, and (2) to disclose PD technique-related predictors of progression of disease during a 24-month follow-up period. We used vascular ultrasound for characterization of subclinical atherosclerotic disease. Main Results: A total of 123 patients (51.9%) vs. 79 controls (33.5%) presented ≥1 carotid plaque, and 114 patients (48.3%) vs. 72 controls (30.5%) ≥1 femoral plaque, at baseline evaluation (p < 0.0005). Progression of disease, either in clinical or ultrasound (new plaques) terms, affected 62.6% of patients. Multivariate analysis identified age, carotid intima-media thickness, presence of ≥1 carotid plaque, and serum levels of 25OH vitamin D and C-reactive protein (CRP) at baseline as independent correlates of progression of atherosclerotic disease. On the contrary, PD technique-related variables did not show any association with this outcome. Conclusions: Atherosclerotic vascular disease is frequent among asymptomatic patients undergoing PD. Older age, pre-existent disease (assessed by vascular ultrasound), and serum levels of 25OH vitamin D and CRP are independent markers of the progression of this condition. These findings may contribute to improve identification of subpopulations with a high risk of CV events, deserving intensified measures of prevention.

Evaluating the risk of cardiovascular disease in peritoneal dialysis patients

Evaluating the risk of cardiovascular disease in peritoneal dialysis patients

Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P<0.001, and 39.4 ± 10.1% versus 27.2 ± 11.5%, P=0.002, respectively), lower IGFBP-1 (8.2 ± 7.2 versus 21.0 ± 16.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P<0.001). Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance.

Circulating bacterial-derived DNA fragment level is a strong predictor of cardiovascular disease in peritoneal dialysis patients.

BackgroundCirculating 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.MethodsWe 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.ResultsThe 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).ConclusionsCirculating 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.

Abdominal Aortic Calcification is an Independent Predictor of Cardiovascular Events in Peritoneal Dialysis Patients

Abdominal aortic calcification (AAC) is reported as a predictor for cardiovascular events in general population and in hemodialysis patients. At present, there are no AAC data in peritoneal dialysis. The purpose of this study was to evaluate the prognostic role of AAC score on cardiovascular events in peritoneal dialysis patients. Seventy-four peritoneal dialysis patients were enrolled. AAC was measured on baseline lateral abdomen radiographs by the semi-quantitative method as described by Kauppila. The other cardiovascular risk factors were obtained from patient history and blood examination. The Kaplan-Meier method was used to evaluate freedom from cardiovascular events, and differences were assessed with the log-rank statistic. Multivariate Cox regression models addressed time to cardiovascular events. The median period of follow-up was 30.5months (IQR 19.4-32.7). During follow-up, there were 29 cardiovascular events (39.2%). In univariable analysis, patient's age (HR=1.050; P=0.001), urine output (HR=0.999; P=0.02), and AAC stratified by tertiles (overall P-value<0.001) were significantly associated with cardiovascular events. In multivariable regression analysis, AAC score stratified by tertiles was the only independent predictor for cardiovascular events (overall P-value<0.001). To our knowledge, we have shown for the first time that AAC score is an independent predictor of cardiovascular events in peritoneal dialysis patients. Risk stratification by assessment of AAC score may provide important information for the management of cardiovascular disease in peritoneal dialysis patients without any additional expense, because these patients have several abdominal X-ray scans to evaluate the catheter position.

EFFECTS OF SOY CONSUMPTION ON SERUM LIPIDS AND APOPROTEINS IN PERITONEAL DIALYSIS PATIENTS: A RANDOMIZED CONTROLLED TRIAL

Lipid abnormalities, particularly high serum concentration of lipoprotein(a) [Lp(a)], are one of the major risk factors for cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. The present study was designed to investigate the effects of soy consumption on serum lipids and apoproteins, especially Lp(a), in PD patients .This study was a randomized clinical trial in which 40 PD patients (20 males, 20 females) were randomly assigned to either the soy or the control group. Patients in the soy group received 28 g/day textured soy flour (containing 14 g of soy protein) for 8 weeks, whereas patients in the control group received their usual diet, without any soy. At baseline and the end of week 8 of the study, 5 mL of blood was collected from each patient after a 12- to 14-hour fast and serum triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apoprotein B100 (apo B100) apoprotein A (apo AI), and Lp(a) were measured. In the present study, serum Lp(a) concentrations were above the normal range in 86% of the PD patients. Mean serum Lp(a) concentration was reduced significantly, by 41%, in the soy group at the end of week 8 compared to baseline (p < 0.01); the reduction was also significant compared to the control group ( p < 0.05). During the study, mean serum Lp(a) concentration did not change significantly in the control group. There were no significant differences between the two groups in mean changes in serum triglyceride, total cholesterol, HDL-C, LDL-C, apoB100, or apoAI. The results of our study indicate that soy consumption reduces serum Lp(a) concentration, which is a risk factor for cardiovascular disease in peritoneal dialysis patients.

Visceral Fat Thickness Is Associated With Carotid Atherosclerosis in Peritoneal Dialysis Patients

Visceral fat has been known to associate with atherosclerosis, inflammation, and insulin resistance. However, the influence of visceral fat on cardiovascular disease (CVD) in peritoneal dialysis (PD) patients has never been elucidated. We investigated whether visceral fat thickness (VFT) has a predictive role in carotid atherosclerosis determined by carotid intima-media thickness (cIMT) in PD patients. A cross-sectional study was undertaken in 88 prevalent PD patients. BMI and waist circumference (WC) were measured as anthropometric indexes of obesity. VFT and subcutaneous fat thickness (SFT) were determined by sonographic measurement of abdominal fat. Carotid atherosclerosis was defined as increased cIMT (>1.0 mm) or presence of plaque. Thirty-two (36.3%) patients had carotid atherosclerosis. Patients with carotid atherosclerosis showed significantly higher VFT, BMI, and WC. In univariate logistic analysis, BMI, WC, and VFT except SFT were significant risk factors of carotid atherosclerosis. However, multivariate analysis revealed VFT was an independent factor associated with carotid atherosclerosis after adjusting for demographic, biochemical parameters, and anthropometric indexes (per 1 mm increase, odds ratio (OR) = 2.294, 95% confidence interval: 1.048-5.021, P = 0.038). When the patients were divided into three groups according to VFT, log high sensitivity C-reactive protein (hs-CRP), and homeostasis model assessment-insulin resistance (HOMA(IR)) were both higher in the third tertile compared to other tertiles. In conclusion, VFT, not SFT, is independently associated with carotid atherosclerosis in PD patients. Therefore sonographic measurement of VFT could be useful to stratify the risk of cardiovascular disease in PD patients.

Relationship between human oxoguanine-DNA glycosylase-1 polymorphism and the outcome of Chinese peritoneal dialysis patients

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. 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. 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 ≤ 5.0 mg/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 > 5.0 mg/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). 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. 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。 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。 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)。 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。

Relationship between CRP Polymorphism and Cardiovascular Events in Chinese Peritoneal Dialysis Patients

The single-nucleotide polymorphism (SNP) -717A→G substitution, rs2794521, was found in the promoter of the C-reactive protein (CRP) gene. Functional studies showed that A allele promoter has higher transcriptional activity than the G allele. This study investigated the association between this SNP and the outcome of Chinese patients undergoing peritoneal dialysis (PD). The study included 441 new PD patients (232 men; mean age ± SD, 56.7±13.5 years). CRP genotyping was determined; patients were followed for 41.3±18.3 months for cardiovascular events. For the entire cohort, 5-year event-free survival rates did not differ between the AA and AG/GG groups (35.7% and 31.9%, respectively; P=0.64). However, there was significant interaction between plasma cholesterol levels and CRP genotype groups on event-free survival (P=0.04 for interaction). For patients with cholesterol levels of 200 mg/dl or greater, the 5-year event-free survival rate in the AG/GG group was significantly better than that in the AA group (54.7% versus 40.0%; P=0.04), whereas there was no difference in event-free survival between genotype groups for patients with cholesterol levels less than 200 mg/dl. CRP gene -717AG or GG genotypes is associated with cardiovascular benefit to Chinese PD patients with cholesterol levels of 200 mg/dl or greater. These findings suggest a complex interaction among cholesterol, CRP, and cardiovascular disease in PD patients.

Peritoneal Total Protein Transport Assessed from Peritoneal Equilibration Tests Using Different Dialysate Glucose Concentrations

The peritoneal equilibration test (PET) permits assessment of peritoneal protein transport, but this potential marker of outcome in peritoneal dialysis (PD) patients lacks adequate standardization. ♢ To assess various approaches for estimation of peritoneal protein transport in PD patients during 2.27% and 3.86% glucose-based PETs, and to uncover the demographic, clinical, and biochemical correlates of this phenomenon. ♢ We studied 90 PD patients who underwent 2.27% and 3.86% PETs in random order, and we used multivariate analysis to compare assessments of peritoneal protein transport in both tests, searching for correlations between D₂₄₀' - D₀' protein concentration (PETΔPConc), total peritoneal protein excretion (PET-PPE), or total protein clearance (PET-PC) on the one hand (the main study variables), and PET-derived markers of peritoneal function and selected demographic, clinical, and biochemical variables on the other. ♢ The PETΔPConc was higher during the 2.27% PET (mean: 45.2 mg/dL vs 37.0 mg/dL for the 3.86% test; p = 0.003); the PET-PPE and PET-PC were comparable (1121.8 mg vs 1168.9 mg, p = 0.52, and 17.1 mL vs 17.8 mL, p = 0.66, respectively). All three variables sustained a significant, yet moderate correlation (all r² values < 0.30) with the 24-hour PPE rate. Multivariate analysis identified dialysate-to-plasma ratio (D/P₂₄₀') of creatinine, end-to-initial dialysate ratio (D₂₄₀'/D₀') of glucose, current daily peritoneal glucose load, ultrafiltration during PET, systolic blood pressure, and previous cardiovascular events (3.86% test only) as independent predictors of protein transport during PET. ♢ Either PET-PPE or PET-PC seems preferable to PETΔPConc for characterization of peritoneal protein transport. Small-solute transport characteristics, ultrafiltration, and current peritoneal glucose load sustain independent correlations with peritoneal protein transport. The latter variable shows also a moderate association with markers of cardiovascular disease in PD patients.

Effects of Soy Consumption on Serum Lipids and Apoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial

Lipid abnormalities, particularly high serum concentration of lipoprotein(a) [Lp(a)], are one of the major risk factors for cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. The present study was designed to investigate the effects of soy consumption on serum lipids and apoproteins, especially Lp(a), in PD patients. ♢ This study was a randomized clinical trial in which 40 PD patients (20 males, 20 females) were randomly assigned to either the soy or the control group. Patients in the soy group received 28 g/day textured soy flour (containing 14 g of soy protein) for 8 weeks, whereas patients in the control group received their usual diet, without any soy. At baseline and the end of week 8 of the study, 5 mL of blood was collected from each patient after a 12- to 14-hour fast and serum triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apoprotein B100 (apo B100), apoprotein AI (apo AI), and Lp(a) were measured. ♢ In the present study, serum Lp(a) concentrations were above the normal range in 86% of the PD patients. Mean serum Lp(a) concentration was reduced significantly, by 41%, in the soy group at the end of week 8 compared to baseline (p < 0.01); the reduction was also significant compared to the control group (p < 0.05). During the study, mean serum Lp(a) concentration did not change significantly in the control group. There were no significant differences between the two groups in mean changes in serum triglyceride, total cholesterol, HDL-C, LDL-C, apo B100, or apoAI. ♢ The results of our study indicate that soy consumption reduces serum Lp(a) concentration, which is a risk factor for cardiovascular disease in peritoneal dialysis patients.

Visceral Fat, Arterial Stiffness, and Endothelial Function in Peritoneal Dialysis Patients

The relationship between overweight or obesity and mortality in peritoneal dialysis (PD) patients remains controversial. Both pulse-wave velocity (PWV) and endothelial dysfunction are related to an increased risk of cardiovascular disease. However, the association between PWV, endothelial dysfunction, and visceral adipose tissue in PD patients is not well-understood. One hundred and sixteen PD patients were enrolled in this cross-sectional study. The overall fat ratio and visceral-fat level of PD patients were measured by multiple-frequency bioelectrical impedance analysis (BIA). Carotid-femoral pulse-wave velocity (C-F PWV) was measured as an indicator of aortic stiffness. Endothelial function was evaluated by brachial-artery flow-mediated dilation (FMD). The association between these monitored parameters was assessed by statistical analyses. Bivariate correlation analysis showed that C-F PWV was positively correlated with visceral-fat level (r = 0.343, P < .001), whereas FMD was negatively correlated with visceral-fat level (r = -0.354, P < .01). Multiple regression analysis indicated that age, diabetic status, visceral-fat level, and duration of dialysis were determinants of PWV (adjusted R(2) = 0.316, P < .001), whereas visceral-fat level and glucose load were the determinants of FMD (adjusted R(2) = 0.130, P < .01). Visceral-fat level was an independent predictor of PWV and FMD in PD patients, and could be considered one of the risk factors for cardiovascular disease in PD patients.

Relationship Between β1-Adrenergic Receptor Polymorphisms and Cardiovascular Disease in Peritoneal Dialysis Patients

Recent studies show that a common gain-of-function polymorphism of β1-adrenergic receptor (389 Gly→Arg) plays an important role in the pathogenesis of hypertension and heart failure in patients with normal renal function. We studied the relationship between β1-adrenergic receptor polymorphism and cardiovascular disease in peritoneal dialysis (PD) patients. We studied 189 new PD patients. The β 1-adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay. They were then prospectively followed for the development of cardiovascular events. All-cause mortality and duration of hospitalization were also recorded. There were 95 male cases. The mean age was 56.2 ± 14.8 years. Eighty-six (45.5%) patients were diabetic; 81 (42.9%) received beta-blocker therapy. Only one case was homozygous for the mutant CC genotype. The prevalence of GG, GC, and CC genotypes were 34.9%, 64.6%, and 0.5%, respectively. The genotype distribution was significantly different from that predicted by the assumption of Hardy-Weinberg equilibrium ( p < 0.0001). There was no difference in the prevalence of pre-existing cardiovascular disease between genotype groups. Actuarial patient survival was 80.2% and 85.1% at 24 months for the GG and GC/CC genotypes, respectively ( p = 0.53). Event-free survival was 63.6% and 71.5% at 24 months, respectively ( p = 0.26), and the duration of hospitalization was 15.9 ± 3.0 and 16.6 ± 2.3 days per year, respectively ( p = 0.8). The results remained similar when patients with and without beta-blocker treatment were separately analyzed. Our study demonstrates that the β 1-adrenergic receptor polymorphism is not related to cardiovascular disease in PD patients. Nevertheless, the low prevalence of mutant CC genotype in new PD patients suggests that PD patients represent a highly biased population.