Atherosclerosis In Hemodialysis Patients Research Articles

#2647 Assessing atherosclerosis using epicardial adipose tissue in hemodialysis patients: a meta-analysis

Abstract Background and Aims Hemodialysis (HD) patients had higher cardiovascular mortality due to accelerated atherosclerosis in such patients. Epicardial adipose tissue (EAT) thickness is a marker of atherosclerosis and independent predictor of coronary artery disease. The potential use of EAT as an imaging biomarker for cardiovascular disease risk stratification has attracted attention in the recent times. EAT's value in cases of HD hasn't been thoroughly analyzed, though. A meta-analysis of the literature assessing the mean differences in EAT value between HD patients and healthy controls was conducted. Method Pubmed, Google Scholar and Embase databases were searched from inception till 15 January 2024 for studies that measured EAT thickness of adult patients with HD and matched healthy controls. Outcomes included mean difference (MD) and 95% confidence interval (CI) of EAT thickness between the HD patients and the healthy controls. The results were combined using a fixed or random effect model as per heterogeneity among the included studies in Revman 5.4 software. The between-study heterogeneity of effect size was quantified using the Q statistic and I2. The results were represented in forest plots. Statistical significance was determined as P value of less than 0.05. Results Eight studies comprising 757 patients were included in this analysis. EAT thickness were significantly higher in HD patients as compared to healthy controls [MD: 1.88, Confidence Interval (CI): 0.74-3.02, I2 = 98%, P value = 0.001] (Fig. 1). Conclusion This meta-analysis concluded that HD patients are independently associated with higher EAT as compared to healthy controls. The utility of EAT as an imaging biomarker for predicting atherosclerosis in HD patients is promising. EAT represent readily available clinical markers useful in estimating risk of cardiovascular mortality in HD patients.

Combined Prognostic Value of Preprocedural Protein-Energy Wasting and Inflammation Status for Amputation and/or Mortality after Lower-Extremity Revascularization in Hemodialysis Patients with Peripheral Arterial Disease.

Protein-energy wasting is associated with inflammation and advanced atherosclerosis in hemodialysis patients. We enrolled 800 patients who had undergone successful lower-extremity revascularization, and we investigated the association among the Geriatric Nutritional Risk Index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in predicting amputation and mortality. They were divided into lower, middle, and upper tertiles (T1, T2, and T3) according to GNRI and CRP levels, respectively. Regarding the results, the amputation-free survival rates over 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p < 0.0001 for both). A reduced GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p = 0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95% CI 1.30-2.70, p = 0.0007 for T3 vs. T1) independently predicted amputation and/or mortality. When the two variables were combined, the risk was 3.77-fold higher (95% CI 1.97-7.69, p < 0.0001) in patients who occupied both T1 of the GNRI and T3 of CRP than in those who occupied both T3 of the GNRI and T1 of CRP. In conclusion, patients with preprocedurally decreased GNRI and elevated CRP levels frequently experienced amputation and mortality, and a combination of these two variables could more accurately stratify the risk.

Combined predictive value of pre-procedural protein-energy wasting and inflammation status for amputation and/or mortality after lower extremity revascularization in patients on hemodialysis

Abstract Background Although lower extremity revascularization has been commonly performed in chronic hemodialysis (HD) patients with peripheral artery disease (PAD), poorer prognosis after revascularization still remains major problems. Recently, protein-energy wasting (PEW) or malnutrition have been considered to be strongly associated with chronic inflammation and advanced atherosclerosis in HD patients. We investigated the association of geriatric nutritional risk index (GNRI) as a surrogate marker of the PEW, C-reactive protein (CRP) and their joint role with prediction of amputation and/or mortality after lower extremity revascularization in HD patients. Method We enrolled a total of 800 HD patients (age 67±10 years, diabetes 63.3% and critical limb ischemia 52.9%) who successfully underwent lower extremity revascularization [535 with endovascular therapy (EVT) and 265 with bypass surgery]. Patients were divided into tertiles according to pre-procedural GNRI levels; tertile 1 (T1): &amp;lt;88.1, T2: 88.1-96.7and T3: &amp;gt;96.7, and CRP levels; T1: &amp;lt;2.0mg/l, T2: 2.0-12.6mg/l and T3: &amp;gt;12.6mg/l, respectively. Primary outcome was amputation-free survival (AFS). They were followed up for up to 8 years. Results During follow-up period (median: 43 months), 56 (7.0%) patients needed major amputation and 183 (22.9%) patients died. Kaplan-Meier analysis shows that the AFS rates for 8 years were 47.0%, 56.9% and 69.5% in T1, T2 and T3 of GNRI, and were 65.8%, 58.7% and 33.2% in T1, T2 and T3 of CRP, respectively (p&amp;lt;0.0001 in both). After adjustment for male, age, previous coronary artery disease, procedure (EVT vs. bypass surgery), below-knee artery disease and ulcer/gangrene as covariates with p&amp;lt;0.05 by univariate analysis, declined GNRI [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.57-3.07, p&amp;lt;0.0001 for T1 vs. T3] and elevated CRP (HR 1.78, 95%CI 1.24-2.59, p=0.0016 for T3 vs. T1) were identified as independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk of amputation and/or mortality was 3.77-fold higher (95%CI 1.97-7.69, p&amp;lt;0.0001) in the group with T1 of GNRI and T3 of CRP than in that with T3 of GNRI and T1 of CRP (Figure). Addition of GNRI and CRP in a predicting model with established risk factors improved C-statistics (0.661 to 0.716, p=0.0021) greater than that of each alone. Conclusion Among HD patients undergoing lower extremity revascularization for PAD, those with pre-procedural declined GNRI and elevated CRP frequently experienced amputation and/or mortality, furthermore, combination of both variables could more accurately stratify the risk of amputation and/or mortality.

Study of the Relation between Atherosclerosis and Serum Level of 25(OH) Vitamin D among Maintenance Hemodialysis Patients

Abstract Background Cardiovascular (CV) disease is considered the main cause of exceedingly high overall mortality observed in hemodialysis patients. A number of studies have shown variable results on the relationship between 25 (OH) D deficiency and subclinical atherosclerosis. Aim and objectives To measure the relationship of serum 25(OH) D with Carotid intima-media thickness (cIMT) as a surrogate marker for the presence of atherosclerosis in hemodialysis patients, Subjects and methods This was a cross sectional study, was conducted on 90 patients (ESRD) undergoing hemodialysis in The National Institute of Nephrology and Urology divided into two groups: (Group A); included 45 ESRD patients on maintenance hemodialysis with normal carotid intima media thickness, (Group B): included 45 ESRD patients on maintenance hemodialysis with increased carotid intima media thickness during a period of 6 months. Result There were highly significant difference between both groups as regard 1, 25(OH) 2D, ng/ml. Conclusion Our findings suggested that vitamin D deficiency is not an independent predictor of subclinical atherosclerosis in elderly patients after adjusting confounding factors. Future studies to address the association between serum 25(OH) D and the cIMT need to be explored carefully. Finally we came to the conclusion that in patients on HD, the deficiency of vitamin D is related to rising of ESR asan inflammatory marke,

Malnutrition leads to the progression of coronary artery calcification in hemodialysis patients.

Malnutrition is considered a risk factor for cardiovascular disease in patients with chronic kidney disease. However, no in vivo studies have reported on using optical coherence tomography to evaluate the effect of nutritional status on coronary atherosclerosis in hemodialysis patients. We aimed to conduct a detailed analysis of the effect of nutritional status on the coronary arteries in hemodialysis patients. Among 64 hemodialysis patients who underwent percutaneous coronary interventions, 41 that underwent optical coherence tomography imaging were included in this study. And, among them, 24 patients that could also be evaluated using OCT also at the 6-month follow-up were included in this study. The patients were divided into two groups based on nutritional evaluation using the geriatric nutritional risk index. Culprit and non-culprit lesions were evaluated at baseline and after 6 months. In the culprit lesions at baseline, the length of the lipid plaque was significantly smaller in the malnutrition group. In contrast, the thickness and length of the calcified plaque and the angle of the calcified nodule were significantly larger (each p < 0.01). In the non-culprit lesions, the 6-month change in the angle of the calcified plaque was significantly greater in the malnutrition group (p = 0.02). The significant factors that affected the change in the angle of calcification were "malnutrition at geriatric nutritional risk index" [odds ratio, 8.17; 95% confidence interval, 1.79 to 37.33; p < 0.01] and "serum phosphorus level" (odds ratio, 3.73; 95% confidence interval, 1.42 to 9.81; p < 0.01). Appropriate management of nutritional status is crucial for suppressing the progression of coronary artery disease in hemodialysis patients.

The association between platelet to lymphocyte ratio and neutrophil to lymphocyte ratio with inflammatory factors in hemodialysis patients

Introduction: Chronic inflammation is a major factor in the pathogenesis of atherosclerosis in hemodialysis patients compared to healthy individuals. Chronic inflammation is part of the malnutrition, atherosclerosis, and inflammation syndrome in advanced renal failure. Objectives: In this study, the relationships of platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) with the inflammatory factors were investigated. Patients and Methods: This cross-sectional study was conducted on 108 hemodialysis patients who were on dialysis for more than three months. For patients, serum levels of urea, creatinine (Cr), sodium, potassium, calcium, phosphate, parathyroid hormone, total cholesterol, triglyceride, ferritin, 25-hydroxy vitamin D, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood cell count were assessed before dialysis since serum urea was examined again after dialysis too. Results: The mean age of the patients (58 male and 50 female) was 63.43±14.65 years. The median values for NLR and PLR were 2.25 and 114.7, respectively. ESR was significantly higher in hemodialysis patients with NLR &gt;2.25 (46.7±29.7 versus 36±22.7) and in those with PLR &gt;114.7 (47.09±27.8 versus 35.6±24.8). Plasma hemoglobin and serum 25-hydroxy vitamin D levels were observed to be lower (10.37±1.6 versus 11.7±1.8 and 33.1±2.5 versus 37.9±15.2) in patients with PLR &gt;114.7. Bivariate correlation showed that PLR and NLR had positive significant correlation with ESR while PLR had a significant negative correlation with values of blood 25-hydroxy vitamin D hemoglobin and Cr. Conclusion: Due to availability and affordability of PLR and NLR, they could be used for early assessment of inflammation in end-stage renal disease (ESRD) patients. PLR may be better predictor than NLR (to detect inflammation.

Possible effect of dialysis membrane in polymethylmethacrylate on clinical variables associated with atherosclerosis development in chronic renal failure patients

Background: Chronic hemodialysis patients have higher cardiovascular morbidity compared to the general population. A number of studies have suggested that patients undergoing hemodialysis with polymethylmethacrylate (PMMA) membranes have a better outcome compared to other membranes. Methods: We performed a retrospective, multicenter study to evaluate the impact of PMMA membranes compared to other types of membranes on clinical parameters considered important risk factors for the development of cardiovascular disease in chronic kidney disease patients. Results: The study included 104 patients (52 patients on PMMA and 52 patients on other membranes) from ten dialysis centers, monitored for 24 months. HDL cholesterol (mg/dL) increased significantly in the PMMA group (41.4 ± 10.8 to 44.1 ± 13.5, p = 0.0467), but not in the control group (41.8 ± 13.8 to 39.4 ± 9.6, p = 0.8628). At 24 months total cholesterol and triglycerides (mg/dl) were significantly lower in the PMMA group than in the control group (142.4 ± 43.8 vs. 166.1 ± 43.4, p = 0.0321 and 106 (76.5-176) vs. 170 (118-254), p = 0.014), respectively. Serum creatinine (mg/dL) increased significantly from baseline to 24months in the PMMA group (9.20 ± 2.5 to 9.47 ± 2.3, p = 0.0291), but not in the patients treated with other membranes (8.39 ± 2.6 to 8.37 ± 2.3, p = 0.2743). In addition creatinine was significantly higher in the PMMA group compared to the other group (9.47 ± 2.3 vs. 8.37 ± 2.3, p = 0.0493). WBCs (109/L) increased significantly in the control group (6151 ± 1846 to 6672 ± 1872, p = 0.0457) but not in the PMMA group (6326 ± 2113 to 6152 ± 1832, p = 0.8981). At 24 months platelets (109/L) and CRP (ng/dL) were significantly lower in the PMMA group compared to the control group (185 (144-222) vs. 210 (173-259), p = 0.0498 and 0.70 (0.30-1.59) vs. 3.76 (0.46-10.2), p = 0.023, respectively). Iron and transferrin (μ g/dL) decreased signifi cantly in the patients treated with other membrane (62.5 ± 30.4 to 52.6 ±19.0, p = 0.0113 and 178 (157-218) to 170 (124-203), p = 0.0019, respectively), but not in the PMMA group. Conclusion: This retrospective study of data from 104 patients shows a favorable effect of PMMA on clinical variables considered relevant for the development of atherosclerosis in hemodialysis patients.

INVESTIGATION OF THE CLINICAL FACTOR ASSOCIATED WITH INTRADIALYTIC HYPOTENSION: INSIGHT FROM KIDS REGISTRY

Objective: Intradialytic hypotension (IDH) is a major complication during hemodialysis (HD)session, associated with increased risk of cardiovascular events and mortality. Its pathophysiology is believed to be multifactorial and remains not well elucidated. The aim of this study is to investigate the clinical factor associated with IDH. Design and method: The KIDS Registry is a prospective cohort study in patients with maintenance dialysis at 4 facilities in Kagoshima Prefecture in Japan were consecutively enrolled (531 patients) June 2015 to the present. 345 patients who were finished over 1-year follow-up and available blood pressure data during HD were made to be an analysis subject, and divided into two groups according to the severity of decrease in systolic blood pressure (SBP) during HD; hypotension (IDH group, n = 148) and non-hypotension (non-IDH group, n = 197) groups showing an SBP decrease during HD of 20 mmHg or more, and less than 20 mmHg, respectively, compared with the SBP value before HD. Results: Prior peripheral vascular disease (PVD), history of diabetes mellitus (DM), history of hypertension and pre-urea nitrogen value were significantly higher in hypotension group than in non-hypotension group. We performed multivariate logistic regression to test for the independent contribution to IDH. Prior PVD(Odds Ratio (OR): 1.77, 95% Confidence Interval (CI): 1.01 to 3.09), history of DM (OR: 2.34, 95%CI: 1.39 to 3.93), and pre-urea nitrogen value (OR: 1.03, 95%CI: 1.01 to 1.05) were independent associating factors to IDH after adjusted by several clinical relevant factors. Conclusions: Atherosclerotic disease such as PVD and DM which was the important disease leading to atherosclerosis were significant associating factors with IDH. IDH may be associated with atherosclerosis in HD patients.

P1256THE ASSOCIATION PROTEIN-ENERGY WASTING AND INFLAMMATION STATUS WITH MORTALITY AFTER LOWER EXTREMITIES REVASCULARIZATION IN PATIENTS ON HAEMODIALYSIS

Abstract Background and Aims Although lower extremity revascularization has been commonly performed in chronic haemodialysis (HD) patients with peripheral artery disease (PAD), poorer prognosis still remains major problems in such population. Recently, protein-energy wasting (PEW) or malnutrition have been considered to be strongly associated with chronic inflammation and advanced atherosclerosis in HD patients. We investigated the association of geriatric nutritional risk index (GNRI) as a surrogate marker of the PEW, C-reactive protein (CRP) and these joint role with prediction of amputation and/or mortality after lower extremity revascularization in chronic HD patients. Method We enrolled a total of 862 HD patients (age 67±10 years, diabetes 62.9%, critical limb ischemia 53.5%) who successfully underwent lower extremity revascularization (552 with endovascular therapy and 310 with bypass surgery). Patients were divided into tertiles according to GNRI levels; tertile 1 (T1): &amp;lt;80.0, T2: 80.0-96.6and T3: &amp;gt;96.6, and CRP levels; T1: &amp;lt;2.0mg/l, T2: 2.0-12.6mg/l and T3: &amp;gt;12.6mg/l, respectively. They were followed up for up to 8 years. Results During follow-up period (median: 43 months), 63 (7.3%) patients needed major amputation and 202 (23.4%) patients died. Kaplan-Meier analysis shows that amputation-free survival rates for 8 years were 47.5%, 51.6% and 66.5% in T1, T2 and T3 of GNRI, and were 65.8%, 58.7% and 33.2% in T1, T2 and T3 of CRP, respectively (p&amp;lt;0.0001 in both). After adjustment for age, previous coronary artery disease and critical limb ischemia as covariates with p&amp;lt;0.05 by univariate analysis, declined GNRI [hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.57-3.07, p&amp;lt;0.0001 for T1 vs. T3] and elevated CRP (HR 1.78, 95%CI 1.24-2.59, p=0.0016 for T3 vs. T1) were identified as independent predictors of amputation and/or mortality. In the combined setting of both variables, the risk of amputation and/or mortality was 3.77-fold higher (95%CI 1.97-7.69, p&amp;lt;0.0001) in theT1 of GNRI with T3 of CRP than in the T3 of GNRI with T1 of CRP. Similar results were obtained for amputation and mortality, respectively (Figure). Conclusion Among HD patients undergoing lower extremity revascularization, those with pre-procedural declined GNRI and elevated CRP frequently experienced amputation and/or mortality, furthermore, combination of both variables could stratify the risk of amputation and/or mortality.

Platelet Lymphocyte Ratio is Associated With Carotid Atherosclerosis in Hemodialysis Patients

Objective: We aimed to demonstrate whether there is a correlation between Platelet Lymphocyte Ratio (PLR) and carotid intima-media thickness (CIMT) which is an early marker of atherosclerosis in patients receiving dialysis where there is a chronic inflammatory process in the body.Methods: 53 patients receiving dialysis 3 days a week and 54 persons as the control group were included. The exclusion criteria were determined as infection, using drugs that increase or decrease the number of leukocytes such as steroids, antithyroid, chronic liver diseases, rheumatic disease, maling disease and prior cardiovascular or cerebrovascular diseases. Patients’ age, gender, body mass index, hemogram and biochemical parameters were recorded. CIMT values were measured by Carotid Doppler examination.Results: When the two groups were compared; there was no significant difference between them in terms of age, gender, blood pressures, DM, ejection fractions, lipid levels. PLR, neutrophil-to-lymphocyte ratio (NLR) and CIMT were significantly higher (p=0.009, p&amp;lt;0.001, p&amp;lt;0.001; respectively) in the dialysis patients group. A positive correlation was found between CIMT and PLR, NLR (r=0.59 p&amp;lt;0.001, r=0.38, p=0.004). As a result of the linear regression analysis, PLR (B:0.714, 95%CI:3.425/14.393, p=0.002) and NLR were found as independent predictors in showing CIMT. Conclusion: PLR is independently associated with subclinical atherosclerosis assessed by CIMT in people with dialysis patients

Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients.

The purpose of this study was to determine the prevalence of oral Candida spp. in HD patients and to investigate its relation with systemic inflammation and atherosclerosis. Microbiological samples were taken from buccal mucosa, palate, and dental prosthesis with a cotton swab. High-sensitivity CRP (hsCRP) and IL-6 were measured as inflammation markers. A total of 69 patients (58% male and median age 62 years) were enrolled in this study; 53.6% of total patients had oral Candida colonization. HsCRP and IL-6 levels were found to be significantly higher in the oral Candida colonization positive group than in the Candida colonization negative group (P = 0.002 and P = 0.01, respectively). HDL levels were significantly lower in the Candida colonization positive group (P = 0.03). Peripheral artery disease (P = 0.05) and oral Candida colonization (P = 0.002) were significantly associated with inflammation. In addition to conventional risk factors such as age (P = 0.03), diabetes (P = 0.001), and peripheral artery disease (P = 0.002), oral Candida colonization is associated with coronary artery disease (P = 0.04). Oral Candida colonization might be associated with chronic inflammation and development of atherosclerosis in HD patients.

Relationship between visceral obesity and atherosclerosis in hemodialysis patients

Objective: To evaluate the relationship between surrogate markers of visceral obesity[hypertriglyceridemic waist (HW) phenotype, visceral adiposity index (VAL), lipid accumulation product (LAP)]and atherosclerosis in hemodialysis patients. Methods: A multi-center cross-sectional study was carried out. A total of 961 maintenance hemodialysis (MHD) patients from 11 hemodialysis centers of Guizhou province between July 2016 and September 2017 were enrolled in the study. Anthropometric measures were performed in all subjects. Laboratory parameters including triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein-cholesterol were extracted from the medical records by researchers. Pearson correlation analysis was used to investigate the correlation between HW phenotype, VAI, LAP and plasma atherosclerotic index (AIP). Multivariate linear regression analysis was used to evaluate factors affecting AIP. Results: Totally, 585 men and 376 women aged 18-90 years, with a mean age of (56.08±15.42) years were recruited in the study. Pearson correlation analysis showed that VAI (men: r=0.82, women: r=0.84), LAP (men: r=0.73, women: r=0.74) and having HW phenotype (men: r=0.62, women: r=0.63) correlated positively with AIP (all P<0.001). Multivariate linear regression analysis showed that VAI (men: β=0.77, women: β=0.82) and LAP (men: β=0.73, women: β=0.73) were independent associated factors of AIP after adjustment of BMI, age, smoking and history of diabetes and hypertension (all P<0.001). Conclusions: Surrogate markers of visceral obesity such as having HW phenotype, VAI, LAP correlated positively with AIP. VAI, LAP has positive impacts on AIP independent of BMI, age, smoking and other traditional atherosclerosis risk factors.

Relation between high serum hepcidin-25 level and subclinical atherosclerosis and cardiovascular mortality in hemodialysis patients.

Objective:In hemodialysis (HD) patients, cardiovascular disease (CVD) is the major cause of mortality and morbidity. In atherosclerotic diseases, iron gets accumulated in the arterial wall. Hepcidin is an important hormone in iron metabolism. Furthermore, hepcidin is associated with atherosclerotic disease. Therefore, this study aims to investigate the relation of serum hepcidin-25 (SH-25) and sub-clinic atherosclerosis measured by carotid intima-media thickness (CIMT) and mortality in HD patients.Methods:We enrolled 82 HD patients in a cross-control study. We measured SH-25 using ELISA kit and CIMT using high-resolution real-time ultrasonography. After 4 years of first assessment, we investigated the relation between all-cause and cardiovascular mortality and SH-25 and CIMT.Results:Two patients were excluded because of renal transplantation. The survivors were younger (53.7±15.1 vs. 65.2±15.5; p<0.05) and CIMT was lower (0.83±0.2 vs. 0.95±0.2; p<0.05); however, there was no significant difference in SH-25 levels between the groups (29.1±13 vs. 32.4±22.4; p=0.767). The patients who died of CVD were significantly older (63.7±16.1 vs. 53.7±15.1; p<0.05) and had significantly higher CIMT (0.94±0.2 vs. 83±0.2; p<0.05). The SH-25 levels were statistically significantly higher in patients who died of CVD (40.3±25 vs. 29.1±13; p<0.05). Linear regression analysis showed a positive correlation between CIMT and SH-25 in the study population and in those who died from CVD (r=0.41; p<0.05 and r=0.606; p<0.05, respectively).Conclusion:This study suggests that hepcidin is effective in cardiovascular mortality and pathophysiology of subclinical atherosclerosis in HD patients.

Does Neutrophil to Lymphocyte Ratio Tell Something About Atherosclerosis in Hemodialysis Patients?

Does Neutrophil to Lymphocyte Ratio Tell Something About Atherosclerosis in Hemodialysis Patients?

OP-087 [AJC » Preventive cardiology] Profilin-1 as a New Potential Biomarker on Diagnosis of Early Atherosclerosis in Hemodialysis Patients

OP-087 [AJC » Preventive cardiology] Profilin-1 as a New Potential Biomarker on Diagnosis of Early Atherosclerosis in Hemodialysis Patients

Plasma Fibroblast Growth Factor-23 Level and its Relation to Carotid Artery Atherosclerosis in Hemodialysis Patients

Plasma Fibroblast Growth Factor-23 Level and its Relation to Carotid Artery Atherosclerosis in Hemodialysis Patients

Elevation of Platelet and Monocyte Activity Markers of Atherosclerosis in Haemodialysis Patients Compared to Peritoneal Dialysis Patients.

Purpose The predominant cause of mortality in dialysis patients are cardiovascular events. Platelet and monocyte activity markers play an important role in cardiovascular mortality and were assessed and related to dialysis quality criteria in haemodialysis (HD) and peritoneal dialysis (PD) patients. Methods For this prospective comparative study, HD patients (n = 41) and PD patients (n = 10) were included. In whole blood samples, surface expression of CD62P and CD40L on platelets, tissue factor binding on monocytes, and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of MCP-1, IL-6, TNFα, and soluble CD40L were analysed by enzyme-linked immunosorbent assay. Results Haemodialysis patients showed a significantly higher CD62P expression on platelets (p = 0.017), significantly higher amount of platelet-monocyte aggregates (p < 0.0001), and significantly more tissue factor binding on monocytes (p < 0.0001) compared to PD patients. In PD patients, a significant correlation between Kt/V and platelet CD40L expression (r = 0.867; 0.001) and between Kt/V and platelet CD62P expression (r = 0.686; p = 0.028) was observed, while there was no significant correlation between Kt/V and tissue factor binding on monocytes and platelet-monocyte aggregates, respectively. Conclusion Platelet and monocyte activity markers are higher in HD patients in comparison with those in PD patients, possibly suggesting a higher risk of cardiovascular morbidity and mortality.

New Insight into Atherosclerosis in Hemodialysis Patients: Overexpression of Scavenger Receptor and Macrophage Colony-Stimulating Factor Genes

Background: Scavenger receptors (SRs) play a pivotal role in atherogenesis. The mechanism of atherosclerosis, which is specific to hemodialysis (HD) patients, was studied on the basis of SR gene expressions. Methods: The gene expressions of SR type A (SR-A) and CD36 were studied in peripheral monocytes by real-time reverse transcription polymerase chain reaction. Data were compared between HD (n = 30) and age-matched control subjects (n = 10). Serum levels of macrophage colony-stimulating factor (M-CSF) were measured with enzyme-linked immunosorbent assay to test its role in SR expression. The statistical differences and associations between two continuous variables were assessed using the Mann-Whitney U test and Pearson's correlation coefficient, respectively. Results: The relative quantities of SR mRNAs were significantly greater in HD patients than in controls [median (interquartile range): SR-A, 1.67 (0.96-2.76) vs. 0.90 (0.60-1.04), p = 0.0060; CD36, 1.09 (0.88-1.74) vs. 0.74 (0.64-0.99), p = 0.0255]. The serum concentration of M-CSF was significantly higher in HD patients than in controls [1,121 (999-1,342) vs. 176 (155-202) pg/ml, p < 0.0001]. In addition, the relative quantity of M-CSF mRNA was significantly greater in HD patients than in controls [0.79 (0.42-1.53) vs. 0.42 (0.28-0.66), p = 0.0392]. The serum M-CSF levels were positively correlated with both the relative quantity of SR-A mRNA (r² = 0.1681, p = 0.0086) and that of CD36 mRNA (r² = 0.1202, p = 0.0284) in all subjects (n = 40). Conclusion: HD patients are predisposed to atherosclerosis as a consequence of their enhanced monocyte SR expressions. SRs and M-CSF are potential therapeutic targets for atherosclerosis in this high-risk population.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients.

Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

FGF-23 levels are associated with vascular calcification, but not with atherosclerosis, in hemodialysis patients.

High fibroblast growth factor-23 (FGF-23) levels are associated with mortality and cardiovascular events in patients with chronic kidney disease. The aim of this cross-sectional study was to investigate the relationship between plasma FGF-23 levels and coronary artery calcification and carotid artery intima-media thickness (CA-IMT) in hemodialysis (HD) patients. In this cross-sectional study, plasma intact FGF-23 levels were measured in 229 patients who underwent coronary artery calcification scores (CACs) determined by multi-slice computerized tomography and CA-IMT assessed by using high-resolution color Doppler ultrasonography. Median FGF-23 was 53.5 pg/ml (IQR 30.8-249.5). Median CACs was 98 (IQR 0-531), and the frequency of patients with severe calcification (CACs > 400) was 28.8%; 27.5% of cases had no calcification. Mean CA-IMT was 0.78 ± 0.20 mm, and the presence of carotid plaques was 51% with a mean length 2.1 mm. FGF-23 level was positively correlated with serum calcium (r = 0.337, p < 0.001), phosphate (r = 0.397, p < 0.001) and CACs (r = 0.218, p = 0.001). Neither CA-IMT nor the presence of carotid artery plaques correlated with FGF-23 levels. In adjusted ordinal regression analysis, FGF-23 level was an independent predictor for severe CACs together with age, gender, presence of diabetes, time on dialysis and CA-IMT (model r(2) = 0.44, p < 0.001). As a novel finding, the mean CACs was markedly higher in patients with FGF-23 level above median regardless of phosphate levels (p = 0.03). In HD patients, plasma FGF-23 level is superior to phosphate in the prediction of coronary artery calcification. However, FGF-23 is not associated with carotid artery atherosclerosis in HD patients.