Cardiovascular Disease In Hemodialysis Patients Research Articles

The role of intact parathyroid hormone, total calcium and inorganic phosphate in prediction of cardiovascular disease in hemodialysis patients

The role of intact parathyroid hormone, total calcium and inorganic phosphate in prediction of cardiovascular disease in hemodialysis patients

Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients

Introduction: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. Methods: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. Results: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. Conclusions: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

#5216 DIALYSIS MODALITIES, URAEMIC TOXINS AND MICROINFLAMMATION: CAN WE DO MORE?

Abstract Background Patients on hemodialysis (HD) have a high morbidity and mortality from cardiovascular disease (CVD). Despite advances in HD -new membranes, such as medium cut-off (MCO) or techniques that combine diffusion+convection+adsorption such as hemofiltration with ultrafiltrate regeneration- (HFR)-, only online hemodiafiltration (OL-HDF) has been shown to improve survival in these patients. It is important to investigate whether the new HD filters/techniques help to improve the clearance of uremic toxins that are difficult to eliminate (those bound to proteins) and molecules associated with microinflammation in uremic patients, due to the important role they play in the development of CVD. Aim To study whether different HD membrane-techniques improve the clearance of uremic toxins and/or parameters associated with the microinflammation present in these patients. Method 12 stable patients on HD were included, with a minimum time on HD of 3 months. Each patient underwent 4 random HD sessions in which only the dialysis membrane and/or the modality were changed. They underwent an HD session with a high-flux polyphenylene membrane, another session with this same filter in OL-HDF, another with MCO membrane, and another with HFR-H. All sessions were held in a short period. In all of them, pre- and post-dialysis blood samples were taken to assess the clearance of both conventional uremic toxins and protein-bound toxins (indoxyl-sultate and p-cresol), as well as molecules associated with the microinflammation process (proinflammatory monocytes: CD14+/CD16++ and proinflammatory cytokines). Results When evaluating the effect of the different HD techniques on the percentage of proinflammatory monocytes, a relevant, although not significant, decrease was observed in the OL-HDF and HFR-H techniques. Likewise, when evaluating the profile of markers of inflammatory activity, such as IL-12B, IL-17C, CD8A or TNFRSF9, a significant decrease was observed after the dialysis session in HFR-H compared to the rest of the techniques analyzed. Conclusion After analyzing the results of our study, the HD technique that combines convection+adsorption+diffusion (with a novelty high permeability filter), HFR-H, is the only one that has shown significantly greater clearance of proinflammatory cytokines, as well as a greater elimination of activated monocytes and protein-bound toxins, although without reaching statistical significance. These results, although preliminary, are promising and open up a new line of research to improve CVD in HD patients.

Association of circulating MtDNA with CVD in hemodialysis patients and in vitro effect of exogenous MtDNA on cardiac microvascular inflammation

BackgroundChronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.MethodsForty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and erythrocyte sedimentation rate (ESR) were measured by standard assays. Ten-year CVD risk was calculated from the Framingham risk score (FRS) model. In vitro study, human cardiac microvascular endothelial cells (HCMECs) were incubated with normal or uremic serum, with or without exogenous MtDNA. Intracellular toll-like receptor 9 (TLR9), adhesion molecule 1 (ICAM-1), MCP-1 and tumor necrosis factor-α (TNF-α) and cytosolic MtDNA were detected by qPCR.ResultsPlasma MtDNA in MHD patients was significantly higher than healthy controls (4.74 vs. 2.41 × 105 copies/mL; p = 0.000). Subsequently, the MHD patients were classified into two groups based on the MtDNA median (4.34 × 105 copies/mL). In stratified analyses, the levels of Hs-CRP (5.02 vs. 3.73 mg/L; p = 0.042) and MCP-l (99.97 vs. 64.72 pg/mL; p = 0.008) and FRS (21.80 vs. 16.52; p = 0.016) in the high plasma MtDNA group were higher than those in the low plasma MtDNA group. In vitro study, we found that exogenous MtDNA aggravated uremic serum-induced microvascular inflammation (ICAM-1 and TNF-α) in HCMECs (all p < 0.05). Besides, the addition of MtDNA to the medium resulted in a further increase in cytosolic MtDNA and TLR9 levels in uremic serum-treated cells (all p < 0.05). In patients with MHD, MtDNA levels in plasma were significantly reduced after a single routine hemodialysis (pre 4.47 vs. post 3.45 × 105 copies/mL; p = 0.001) or hemodiafiltration (pre 4.85 vs. post 4.09 × 105 copies/mL; p = 0.001). These two approaches seem similar in terms of MtDNA clearance rate (21.26% vs. 11.94%; p = 0.172).ConclusionsOverall, the present study suggests that MtDNA released into the circulation under the uremic toxin environment may adversely affect the cardiovascular system by exacerbating microvascular inflammation, and that reducing circulating MtDNA might be a future therapeutic strategy for the prevention of MHD-related CVD.

Not baseline but time-dependent erythropoiesis-stimulating agent responsiveness predicts cardiovascular disease in hemodialysis patients receiving epoetin beta pegol: A multicenter prospective PARAMOUNT-HD Study

BackgroundResponsiveness to erythropoiesis-stimulating agents (ESAs) has been reported to be associated with increased cardiovascular disease (CVD) and mortality in patients undergoing hemodialysis (HD). However, the association between hyporesponsiveness to the long-acting ESA, epoetin beta pegol (CERA), and CVD remains unknown. MethodsThis multicenter prospective study included 4034 patients undergoing maintenance HD. After shifting from prior ESA to CERA, we studied the association between erythropoietin resistance index (ERI) at six months and outcomes, including cardiac events, major adverse cardiovascular events (MACE), and all-cause mortality, using Cox proportional hazards models (Landmark analyses) and marginal structural models to adjust for time-dependent confounding factors, including iron-containing medications and hemodiafiltration (HDF). ResultsThe median dialysis vintage and the observational period were 5.0 years and 22.1 months, respectively. The landmark analyses revealed that the highest tertile of baseline ERI (T3) was associated with a significantly higher all-cause mortality than the lowest tertile (T1) (hazard ratio [HR]: 1.48, 95% CI: 1.03–2.13). Furthermore, marginal structural models revealed that time-dependent ERI T3 was significantly associated with increased cardiac events (HR: 1.59, 95% CI: 1.14–2.23), MACE (HR: 1.60, 95% CI: 1.19–2.15), all-cause mortality (HR: 1.97, 95% CI: 1.40–2.77), and heart failure (HF) (HR: 2.05, 95% CI: 1.23–3.40) compared to T1. A linear mixed effects model showed that iron-containing medications and HDF are negatively associated with time-dependent ERI. ConclusionsBaseline ERI at six months predicted only all-cause mortality; however, time-dependent ERI was a predictor of cardiac events, all-cause mortality, MACE, and HF. The widespread use of iron-containing medications and HDF would ameliorate ESA hyporesponsiveness.

Clinical characteristics and management of hemodialysis patients with pre-dialysis hypertension: a multicenter observational study

Background Hypertension is a leading preventable risk factor for cardiovascular disease in hemodialysis patients. Pre-dialysis systolic blood pressure (SBP) more than 160 mmHg was thought to be associated with increased risk of cardiovascular events and all-cause mortality. The present study was performed to explore the clinical characteristics and management of hemodialysis patients with pre-dialysis SBP ≥ 160 mmHg. Methods A total of 1233 patients undergoing hemodialysis from nine hemodialysis centers were enrolled. Pre-dialysis and home BP were measured and clinical data were collected. The characteristics of patients with pre-dialysis SBP ≥ 160 mmHg were explored. Clinical parameters between hypertensive and non-hypertensive patients were compared. The partial correlation analyses performed to identify the associations between BP and clinical parameters. Results There were 24.6% of the hemodialysis patients had pre-dialysis SBP ≥ 160 mmHg and the average SBP was 173.8 ± 10.9 mmHg. Only 21.4% of the patients achieved dry weight after dialysis and up to 30.2% of patients were not given combination therapies of antihypertensive drugs. Compared to patients with pre-hemodialysis SBP < 160 mmHg, patients with pre-dialysis SBP ≥ 160 mmHg had lower target-reaching rate of Kt/v and higher incidences of intradialytic hypotension and muscle spasm. Most patients (96%) with pre-dialysis SBP ≥ 160 mmHg had home SBP≥ 135 mmHg. Patients with home SBP ≥ 160 mmHg had higher left ventricular weight index and lower hemoglobin levels when compared to their counterparts with home SBP <160 mmHg. Conclusions Pre-dialysis SBP ≥ 160 mmHg is common in clinical practice and most of the patients could diagnosed to be hypertensive according to their home SBP. Patients with pre-dialysis SBP ≥ 160 mmHg are more likely to be subjected to dialysis insufficiency and intradialytic complications. Achieving dry weight and sufficient pharmacologic interventions should be strengthened to improve BP control in the hemodialysis population.

The Effects of Nigella Sativa Oil on Serum Levels Inflammatory Markers, Oxidative Stress Markers, and Lipid Profile in Dialysis Patients: A Double-Blind Clinical Trail

Background: High concentrations of serum inflammatory and oxidative stress markers and lipid abnormities are important risk factors for cardiovascular diseases in hemodialysis patients. This study aims to investigate the effects of Nigella sativa oil on serum levels inflammation and oxidative stress markers and lipid profile in hemodialysis patients.&#x0D; Methods: Fifty hemodialysis patients participated in this randomized, double-blind, placebo-controlled clinical trial. The patients were randomly assigned into two groups, including receiving 2 tablets of Nigella sativa oil (1000 mg/day, NG) and receiving placebo (PG), for 8 weeks. Blood samples were taken from the patients at the beginning and the end of the study after 12 to 14 hour fasting for measuring serum markers. Then, levels of triglycerides (TG), total cholesterol (TC), LDL-c, HDL-c, high sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured.&#x0D; Results: Consumption of Nigella sativa oil as a supplement decreased levels of TC (P = 0.0002), LDL-c (P = 0.001), mean serum hs-CRP, and MDA compared to the PG (P = 0.001).&#x0D; Conclusion: The Nigella sativa oil supplement may reduce serum hs-CRP and MDA, TC, LDL-c, and risk factors for cardiovascular diseases in hemodialysis patients.

Plasma C4 level was associated with mortality, cardiovascular and cerebrovascular complications in hemodialysis patients

BackgroundPatients on maintenance hemodialysis (HD) exhibit a high risk of death, cardiovascular and cerebrovascular diseases (CCDs). Previous studies indicated complement activation associated with the increased risk of cardiovascular diseases in HD patients. This study aimed to explore whether the critical complement factors were associated with the adverse outcomes in HD patients.MethodsA total of 108 HD patients were included and followed up for 52 months. The baseline clinical characteristics and plasma C3c, C1q, CFH, CFB, C4, MAC, C5a, C3a and MBL were measured. The three endpoints were death, cardiovascular and cerebrovascular events (CCEs) and the composition of them. Univariate and multivariate Cox regression identified factors associated with the three endpoints respectively. X-tile analyses determined the optimal cut-off values for high risks. Restricted cubic spline plots illustrated the dose–response relationships. Correlations between the complement factors and risk factors for CCDs were analyzed.ResultsBaseline plasma C4 was finally selected by univariate and multivariate Cox regression analyses for three endpoints, including all-cause mortality, CCEs and the composition of them. When baseline plasma C4 exceeded 0.47 (P = 0.001) or 0.44 (P = 0.018) g/L respectively, the risks for death or achieving the composite endpoint enhanced significantly. The relationships of C4 and HR for the three endpoints showed a positive linear trend. Plasma C4 had prominent correlations with blood TG (r = 0.62, P < 0.001) and HDL (r = -0.38, P < 0.001).ConclusionsA higher baseline plasma C4 level was significantly associated with the future incidence of decease, CCEs and either of them. Plasma C4 level correlated with blood TG and HDL.

Association of Permanent Vascular Access Dysfunction with Subsequent Risk of Cardiovascular Disease: A Population-Based Cohort Study.

A functional permanent vascular access (VA) is required to perform a successful hemodialysis procedure. Hemodialysis VA dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population. Cardiovascular disease (CVD) is the leading cause of death in patients receiving chronic hemodialysis. Information about CVD associated with hemodialysis VA dysfunction is unclear. We analyzed the association between dialysis VA dysfunction and the risk of developing CVD in hemodialysis patients. This nationwide population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan. One million subjects were sampled from 23 million beneficiaries and data was collected from 2000 to 2013. Patients with end-stage renal disease who had received permanent VA construction and hemodialysis and were aged at least 20 years old from 2000 to 2007 were included in the study population. The primary outcome was CVD, as defined by ICD-9-CM codes 410–414 and 430–437. A total of 197 individuals with permanent VA dysfunction were selected as the test group, and 100 individuals with non-permanent VA dysfunction were selected as the control group. Compared with the control group, the adjusted hazard ratio of CVD for the VA dysfunction group was 3.05 (95% CI: 1.14–8.20). A Kaplan–Meier analysis revealed that the cumulative incidence of CVD was higher in the permanent VA dysfunction group than in the comparison group. Permanent VA dysfunction is significantly associated with an increased risk of subsequent CVD.

Long-term predialysis blood pressure variability and outcomes in hemodialysis patients.

Blood pressure variability (BPV) is significantly associated with cardiovascular diseases (CVD) and mortality in hemodialysis patients. However, the relationship between blood pressure and CVD in hemodialysis patients is complex and affected by many factors. The present study aimed to assess the association of long‐term predialysis BPV with all‐cause mortality and major adverse cardiovascular events (MACE). One thousand seven hundred twenty‐seven patients receiving maintenance hemodialysis were recruited in nine hemodialysis centers. Predialysis BPV was assessed over 1‐year intervals. Outcomes included all‐cause mortality and MACE during follow‐up periods. The mean age of the final cohort was 59 years, of which 57% were males. Greater predialysis systolic BPV was associated with an increased risk of all‐cause mortality (adjusted hazard ratio, 1.101; 95% confidence intervals 1.064–1.140) and MACE (adjusted hazard ratio, 1.091; 95% confidence intervals 1.059–1.125). Results were similar when systolic BPV was stratified by baseline systolic blood pressure. In conclusion, greater predialysis BPV among hemodialysis patients was associated with all‐cause mortality and MACE. Strategies to reduce blood pressure variability might be beneficial for hemodialysis patients.

Relationship between Plasma Trimethylamine-N-Oxide and Cardiovascular Disease in Hemodialysis Patients

Relationship between Plasma Trimethylamine-N-Oxide and Cardiovascular Disease in Hemodialysis Patients

Correlation of Serum Adropin Levels with Risk Factors of Cardiovascular Disease in Hemodialysis Patients.

Background: Many preclinical studies have shown that adropin has physiological effects such as regulating glucose, lipid, and energy metabolism, protecting endothelial cells and antiatherosclerosis. Our aim is to explore whether adropin is correlated with risk factors of cardiovascular disease (CVD) in hemodialysis (HD) patients. Methods: We recruited 170 HD patients and 120 healthy controls. The serum adropin concentration and clinical characteristics were measured. Results: The serum adropin concentration in HD patients was significantly lower than that in healthy controls and which in HD patients with CVD or diabetes mellitus (DM) was significantly lower than that in patients without CVD or DM. The correlation analysis showed that serum adropin levels were correlated negatively with Age, CVD history, DM history, C-reactive protein, type B natriuretic peptide, phosphorus, intact parathyroid hormone, carotid artery plaque amount and carotid intima-media thickness (CIMT), left ventricular septal thickness (LVSTd), and left ventricular posterior wall thickness, whereas it was correlated positively with albumin, hemoglobin, serum creatinine and Kt/V, and ejection fraction value. Partial correlation analysis verified that serum adropin levels were correlated negatively with CIMT, and multiple linear regression analysis revealed that low serum adropin levels may be one independent predictors of CIMT. However, the partial correlation analysis and multiple linear regression analysis did not identify the significant correlation between serum adropin levels and LVSTd. Conclusions: Our study revealed that serum adropin level is significantly correlated with risk factors of CVD and low serum adropin levels may be a potential predictor of CVD in HD patients.

Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers

β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.

Monocyte-to-Lymphocyte Ratio, an Independent Risk Factor of Survival and Cardiovascular Disease in Hemodialysis Patients: Results from the International MONDO Consortium

Monocyte-to-Lymphocyte Ratio, an Independent Risk Factor of Survival and Cardiovascular Disease in Hemodialysis Patients: Results from the International MONDO Consortium

Calcification Biomarkers, Subclinical Vascular Disease, and Mortality Among Multiethnic Dialysis Patients

IntroductionVascular calcification and stiffness are associated with higher mortality and cardiovascular disease in hemodialysis patients, but the underlying mechanism is not well elucidated and previous studies have been contradictory. We sought to determine the association of circulating calcification biomarkers with calcification, stiffness, and mortality in a multiethnic incident dialysis population.MethodsAmong 391 incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, we examined the cross-sectional associations of baseline fibroblast growth factor 23 (FGF23), desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, and osteoprotegerin (OPG) according to total coronary artery calcium score (CAC, using the Agatston calcification criteria) at baseline, vascular stiffness (pulse wave velocity [PWV]) over 4 study visits, and all-cause mortality.ResultsPatients’ mean age was 55 years; 40% were female, 72% were African American, and 58% had diabetes. Higher OPG and FGF23 were associated with a 1.09-fold (per 5-pmol/l increase in OPG; 95% confidence interval [CI]: 1.01–1.17) and 1.12-fold (per increase of 100 log RU/ml in FGF23; 95% CI: 1.02‒1.34) higher prevalence of CAC, independent of demographics, comorbidities, dialysis factors, and serum klotho levels. Higher OPG was associated with higher baseline PWV. Higher FGF23 was associated with lower PWV over follow-up. dp-ucMGP and fetuin-A were not associated with either CAC or vascular stiffness. After adjustment, circulating biomarkers were not associated with mortality risk.ConclusionSeveral circulating calcification biomarkers were only modestly associated with subclinical cardiovascular disease in an incident multiethnic hemodialysis population; none were associated with mortality. Understanding whether these associations persist in larger, diverse hemodialysis populations is warranted before planning trials.

Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis

BackgroundChronic kidney disease (CKD) patients under hemodialysis show a higher risk of cardiovascular (CV) mortality and morbidity than the general population. This study aims to identify genetic markers that could explain the increased CV risk in hemodialysis. Methods A total of 245 CKD patients under hemodialysis were recruited and followed up for 5 years to record CV events. Genetic analysis was performed using single-nucleotide polymorphisms (SNPs) genotyping by Infinium Expanded Multi-Ethnic Genotyping Array (Illumina, San Diego, CA, USA) comparing patients with and without a history of CV events [161 cardiovascular diseases (CVDs) and 84 no CVDs]. The fixation index (Fst) measure was used to identify the most differentiated SNPs, and gene ontology analysis [Protein Analysis THrough Evolutionary Relationships (PANTHER) and Ingenuity Pathway Analysis (IPA)] was applied to define the biological/pathological roles of the associated SNPs. Partitioning tree analysis interrogated the genotype–phenotype relationship between discovered genetic variants and CV phenotypes. Cox regression analysis measured the effect of these SNPs on new CV events during the follow-up (FU).ResultsFst analysis identified 3218 SNPs that were significantly different between CVD and no CVD. Gene ontology analysis identified two of these SNPs as involved in cardiovascular disease pathways (Ingenuity Pathway) and heart development (Panther) and belonging to 2 different genes: Glucagon-like peptide-1 receptor (GLP1R) and Sarcoglycan delta (SGCD). The phenotype–genotype analysis found a higher percentage of CVD patients carrying the GLP1R rs10305445 allele A (P = 0.03) and lower percentages of CVD patients carrying the SGCD rs145292439 allele A (P = 0.038). Moreover, SGCD rs145292439 was associated with higher levels of high-density lipoprotein (P = 0.015). Cox analysis confirmed the increased frequency of CV events during the 5-year FU in patients carrying GLP1R rs1035445 allele A but it did not show any significant association with SGCD rs145292439.ConclusionsThis study identified GLP1R rs10305445 and SCGD rs145292439 as potential genetic markers that may explain the higher risk of CVD in hemodialysis patients.

Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients.

ObjectiveThe current study aimed to investigate the prevalence and risk factors of restless legs syndrome (RLS) in patients undergoing hemodialysis, as well as the mortality and risks of cardiovascular and cerebrovascular events.MethodsA total of 354 hemodialysis patients from four hospitals were enrolled. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria. The patients were evaluated face-to-face using the IRLSSG rating scale, Epworth Sleepiness Scale (ESS), Hamilton Anxiety Scale, Hamilton Depression Scale, and Pittsburgh Sleep Quality Index (PSQI). The patients were followed up for 9 months. Death was considered an endpoint event. The cardiovascular and cerebrovascular events were investigated.ResultsThe prevalence of RLS in hemodialysis patients was 40.7% and was associated with factors such as duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. The scores of the PSQI, ESS, and Hamilton Depression Scale in the RLS group were significantly higher than those in the non-RLS group (p < 0.05). During follow-ups, the incidence rate of cardiovascular diseases was 18.8% in the RLS group and 8.6% in the non-RLS group (p < 0.005). The IRLSSG rating scores were significantly higher in RLS patients with kidney transplantation failure compared with those without transplantation (p < 0.05).ConclusionThe prevalence of RLS was high in hemodialysis patients. The risk factors of RLS included duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. RLS affected sleep quality and emotion and increased the risk of cardiovascular diseases in hemodialysis patients. RLS was more severe in patients with kidney transplantation failure compared with those without transplantation.

P1514Evaluation of endothelial progenitor cells as cardiovascular prognostic biomarkers in hemodialysis patients

Abstract Background Endothelial cells arise from endothelial progenitor cells (EPCs), which reside in bone marrow vascular niches, and are classified according to specific functional differences. Oxidative stress and inflammation lead to endothelial dysfunction that is a critical event in the initiation and progression of atherosclerotic plaques. Patients with chronic renal failure frequently show endothelial dysfunction and are at a greatly increased risk of developing atherosclerosis. Owing to their ability to partially restore vascular damage, both the number and functional changes in EPCs may be considered as useful prognostic biomarkers of cardiovascular events in hemodialysis (HD) patients. Purpose This study investigated EPC features and several biomarkers of systemic vascular inflammation and carotid atherogenesis in hemodialysis (HD) patients. Methods We studied 104 HD patients (males=55 and females 49, mean age: 51±12 years) and 40 healthy controls (males=20/females=20; mean age: 52±11 years). Isolated EPCs were cultured in the fibronectin-covered culture dishes and counted. EPC markers were studied by flow cytometry (FACS) by using anti-CD34, anti-CD133 and anti-vascular endothelial growth factor receptor 2 (VEGFR-2) antibodies. Serum levels of intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), IL-6, TNF-α, and asymmetric dimethyl-arginine (ADMA) were measured by ELISA method. Carotid intima-media thickness (CIMT) and ratio (CIMR) were also evaluated. Results In our experimental conditions, EPC number was decreased in HD patients when compared to controls (p&lt;0.01). Expression of CD34 was significantly lower in the HD group (p&lt;0.01). Interestingly, EPCs were significantly inversely correlated with serum TNF-α levels in HD patients (r=−0.388, p&lt;0.01) but not in the control group (r=−0.133, p=NS). Furthermore, there was an inverse association between VEGFR-2 positive cells and serum TNF α levels (r=−0.401, p=0.002) in HD patients. In HD patients, there was a positive correlation between ICAM levels with CIMT (r=0.405, p=0.03) and CIMR was positively correlated with VCAM levels (r=0.377, p=0.01) and ADMA (r=0.233, p&lt;0.05). Conclusions Our study shows that EPC number was decreased in HD patients and it was associated with systemic inflammation. TNF-α could activate inhibitory actions on EPC in HD patients. A significant relationship was present between ICAM/VCAM and carotid atherosclerosis, while this was not evident with EPC number. These pathogenic mechanisms can contribute to the high incidence of cardiovascular diseases in HD patients. However, further larger studies should investigate this working hypothesis.

The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial.

Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients. We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200μgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12months of follow-up. There were 102 patients that were randomized. After 1year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1year was increased by 12% in the control group. At 1year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1year with no difference between groups. Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

Hyperhomocysteinemia Associated with Low Muscle Mass, Muscle Function in Elderly Hemodialysis Patients: An Analysis of Multiple Dialysis Centers.

Background The hyperhomocysteinemia was with high prevalence and has been considered as a risk factor for cardiovascular disease in hemodialysis patients. These patients also experienced a high risk of muscle wasting caused by the comorbidity, malnutrition, and low physical activity. We investigated the associations of homocysteinemia with muscle mass, muscle function in elderly hemodialysis patients. Methods A clinical cross-sectional study was conducted on 138 hemodialysis patients aged 65 years and above in seven hospital-based hemodialysis centers in Taiwan. The data on anthropometry, laboratory, and 3-day dietary intake was examined. The skeletal muscle mass (SMM) was measured by the bioelectrical impedance analysis; the SMM was adjusted by height or weight as SMMHt2 (kg/m2) and SMMWt (%). Muscle function was defined as handgrip strength (HGS) (kg) measured by handgrip dynamometer. Statistical analyses were conducted using simple regression and multivariable stepwise regression analysis. Results In the total sample, 74.6 % of hemodialysis patients were hyperhomocysteinemia (≥ 15 μmol/L). The means of SMMHt2, SMMWt, arm lean mass, hand grip strength, and muscle quality were 8.7 ± 1.2, 37.7 ± 5.6, 1.7 ± 0.5, 21.1 ± 7.4, and 10.0 ± 3.0, respectively. The multivariable stepwise regression analysis showed that homocysteinemia level was significantly inversely associated with SMMWt (B-coeff. = -0.03, p = 0.02) in hemodialysis patients above 65 years old, but not with muscle function. ConclusionsHyperhomocysteinemia is common and associated with decreased muscle mass in the elderly hemodialysis patients. Future studies are suggested to explore the impact of the homocysteine-lowering therapy on muscle decline.