Evaluation of association between atherogenic index of plasma and intima‐media thickness of the carotid artery for subclinic atherosclerosis in patients on maintenance hemodialysis

Incidence of cardiovascular diseases in the patients having chronic kidney disease (CKD) is between 25% and 60%. This increased rate is proposed to be associated with “accelerated atherosclerosis.” Increased carotid intima‐media thickness (CIMT) is a subclinical atherosclerosis marker. Small‐dense low‐density lipoprotein particles are a strong risk factor for atherosclerosis. It was shown that atherogenic index of plasma (AIP = log(TG/HDL‐c)) is correlated with size of the lipoprotein particles. We investigated the correlation between AIP and CIMT which is a subclinical atherosclerosis marker, in hemodialysis (HD) patients. A total of 62 persons with 31 patients under HD therapy and 31 volunteers were included in the study. In all the participants, CIMT was measured and AIP were calculated. AIP and CIMT values of the participants were compared with blood pressures, lipid profiles and the other risk factors. AIP (0.39 ± 0.32) and CIMT (0.57 ± 0.13) were found significantly higher in the patient group than in the controls (0.04 ± 0.36 and 0.45 ± 0.119, respectively); (P = 0.0001 and 0.0001, respectively). There was a significant correlation between AIP and increased CIMT in the patient group (P = 0.0001, r = 0.430). Among the lipid parameters, the strongest correlation was found between CIMT and AIP. We demonstrated the significant increase of AIP and CIMT in HD patients. A correlation was found between AIP and CIMT. AIP was found to show a correlation with a greater number of risk factors, both classical and CKD specific, than CIMT. These data suggest that AIP might be a method which can be used both in diagnosis of subclinical atherosclerosis and in deceleration processes of its progression.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Oxidative DNA damage correlates with carotid artery atherosclerosis in hemodialysis patients

Oxidative stress is accepted as a nonclassical cardiovascular risk factor in chronic renal failure patients. The aim of this study was to evaluate the relation between oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine/deoxyguanosine [8‐OHdG/dG] ratio), oxidative stress biomarkers, antioxidant enzymes, and carotid artery intima‐media thickness (CIMT) in hemodialysis (HD) patients. Forty chronic HD patients without known atherosclerotic disease and 48 age‐ and sex‐matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8‐OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. 8‐OHdG/dG ratios and MDA levels were higher; SOD and GPx activities were lower in HD patients compared to controls. HD patients had significantly higher CIMT compared to controls (0.61 ± 0.08 vs. 0.42 ± 0.05, p < 0.001). There was a significant positive correlation between CIMT and 8‐OHdG/dG ratio (r = 0.57, p < 0.01) and MDA levels (r = 0.41, p < 0.01), while there was a significant negative correlation between CIMT and SOD (r = ?0.47, p < 0.01) and GPx levels (r = ?0.62, p < 0.01). It is firstly demonstrated that CIMT is positively correlated with oxidative DNA damage in HD patients without known atherosclerotic disease.     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

应用无创性影像学方法探讨冠状动脉和颅脑动脉粥样硬化相关性及临床价值

目的：探讨冠状动脉和颅脑动脉粥样硬化相关性及其临床应用价值。方法：选取疑似冠心病患者90例,分别进行CT血管造影、颈动脉超声、经颅多普勒超声检查,统计对比相关指标。结果：经CCTA评估轻度狭窄31例、中度狭窄32例、重度狭窄27例;冠状动脉狭窄程度不同患者颈动脉超声检查IMT、斑块数目差异、TCD颅内血管PI、RI指标差异具有统计学意义（P＜0.05）。结论：冠状动脉与颅脑动脉粥样硬化具有一致性,因此冠心病患者应积极诊断、治疗脑血管疾病。     

Important role of blood rheology in atherosclerosis of patients with hemodialysis

Concerning a role of blood rheology for atherosclerosis in patients with hemodialysis (HD), little data are available. It may be due to the fact that the method for evaluating rheologic properties of circulating blood has been limited. We examined blood rheology in 118 HD patients by using microchannel array flow analyzer that makes it possible to directly observe the flow of blood cell elements through the microchannel. Transit time (T(B)) of heparinized whole blood through slit pores (7 x 30 microm) was used as an index of rheology and related with various inflammatory biomarkers such as high-sensitive CRP (hsCRP), monocyte chemotactic protein-1, osteopontin, or fibrinogen (Fg). Moreover, as a surrogate marker of atherosclerosis, carotid intima-media thickness (IMT) and aortic stiffness evaluated by brachial-ankle pulse-wave velocity (baPWV) were studied. In HD patients, T(B) had strong positive correlations with hsCRP (r = 0.427; p < 0.00001), Fg (r = 0.452; p < 0.00001), and osteopontin (r = 0.227; p < 0.0134). Further, T(B) was significantly well correlated with IMT (r = 0.400; p < 0.0001) and PWV (r = 0.470; p < 0.0001). Multivariate regression analysis showed that baPWV, IMT, Fg, hematocrit, white blood cell count, and CRP were chosen as significant explanatory factors for T(B.) These results suggest that blood rheology may play an important role for atherosclerosis in patients with HD.     

Increased leukocyte aggregates are associated with atherosclerosis in patients with hemodialysis

Little data are available on the role of blood rheology in atherosclerosis in hemodialysis (HD) patients. This study sought to assess the relationship between leukocytes conjugated with platelets (leukocyte aggregates [LA]) and atherosclerosis in patients with HD. The present study included 118 patients on HD. As surrogate markers of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were measured. As an assessment of LA, a method, microchannel array flow analyzer, which makes it possible to directly observe the flow of blood cell elements through the microchannel, was used. We measured a number of LA during 50 μL flow of whole blood through microchannels. In 12 age-matched healthy individuals, a number of LA during 50 μL flow of whole blood was 25.7±5.4, whereas in HD patients it was significantly increased up to 48.2±16.4 (P<0.001). Flow cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates were positively associated with plasma levels of fibrinogen (P<0.01), or serum high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001). In conclusion, we demonstrated hemorheologically that monocyte-platelet conjugates play an important role in aortic stiffness and IMT in HD patients.     

Intima-media thickness of carotid arteries and erectile dysfunction in hemodialysis patients

The prevalence of erectile dysfunction (ED) in hemodialysis (HD) is extremely high. The objective of this study was to evaluate the association between the intima-media thickness of carotid arteries and ED in HD patients. The survey was organized as a cross-sectional study in men aged up to 65 years, in the HD. All respondents voluntarily completed the questionnaire of the International Index of Erectile Function-5, adjusted for the Serbian language, verified routine laboratory analysis, calculated body mass index, demographic structure, duration of dialysis, the presence of hepatotropic viruses and erythropoietin therapy, smoking and drinking alcohol, determined the quality of HD, verified significantly comorbidities and measured the intima-media thickness of carotid artery using the Doppler method. The prevalence of ED in our study was 82.2%. Erectile dysfunction significantly more prevalent in older (P = 0.001) and obese patients (P = 0.047). It is significantly represented in patients with cardiovascular disease (P = 0.006), in those who consume alcohol (P = 0.04) and patients with higher values of intima-media thickness of carotid arteries (P = 0.007). Spearman's coefficient of linear correlation (ρ=-0.34, P=0.006) and linear regression (b=-2.02, P<0.001) indicated a negative association between intima-media thickness and the International Index of Erectile Function score. The prevalence of ED in our patients was 82.2%, more common in older and obese patients, a significant determinant of alcohol consumption and cardiovascular disease. Increased thickness of the intima media of the carotid arteries was associated with a higher incidence of ED.     

Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3‐dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3‐dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima‐medial thickness, brachial‐ankle pulse wave velocity, ankle‐brachial pressure index, and the cardio‐ankle vascular index. Log‐transformed Kyn/Trp ratio was significantly correlated with log‐transformed time on HD (ρ=0.28, P<0.01), log‐transformed highly sensitive C‐reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=?0.13, P<0.05). A significant association was found between log‐transformed Kyn/Trp ratio and mean carotid artery intima‐medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima‐medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle‐brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.     

Pre‐ and Post Hemodialysis Procalcitonin Levels and Their Relationships with Immunoregulatory,Proinflammatory Cytokines in Chronic Hemodialysis Patients

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Arteriosclerosis is characterized by stiffening of arteries. Metabolic, inflammatory, and hemodynamic alterations cause structural changes and vascular complications in end‐stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty‐two patients (16 men and 16 women) on chronic HD with a mean age of 42.2 ± 19.3 (range, 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high‐resolution echo‐tracking system. Einc measurement was calculated from transcutaneous measurements of carotid arterial internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance (CCC) and distensibility (CCD) were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Serum levels of calcium (Ca), phosphorus (P), parathormone (PTH), ferritin, C‐reactive protein (CRP), predialysis systolic blood pressure (SBP), predialysis diastolic blood pressure (DBP), pulse pressure (PP), age, HD duration, CCC, and CCD were correlated with Einc in all patients. A significant positive correlation was found between Einc and age (r = 0.40, p < 0.02), SBP (r = 0.39, p < 0.02), PP (r = 0.40, p < 0.02), Ca (r = 0.43, p < 0.01), CRP (r = 0.38, p < 0.02). As expected, Einc was correlated inversely with CCD (r = ?0.77, p < 0.0001). The correlation between Einc and HD duration, DBP, ferritin, P, PTH, and CCC was not significant. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP and PP) but also to metabolic (increased Ca) and inflammatory (increased CRP) responses. Carotid Einc is an accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca‐containing P binder should be used carefully in HD patients.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Manual and automated media and intima thickness measurements of the common carotid artery

The intima-media thickness (IMT) of the common carotid artery (CCA) is widely used as an early indicator of the development of cardiovascular disease (CVD). It was proposed but not thoroughly investigated that the media layer (ML) thickness (MLT), its composition, and its texture may be indicative of cardiovascular risk and for differentiating between patients with high and low risk. In this study, we investigate an automated method for segmenting the ML and the intima layer (IL) and measurement of the MLT and the intima layer thickness (ILT) in ultrasound images of the CCA. The snakes segmentation method was used and was evaluated on 100 longitudinal ultrasound images acquired from asymptomatic subjects, against manual segmentation performed by a neurovascular expert. The mean ± standard deviation (sd) for the first and second sets of manual and the automated IMT, MLT, and ILT measurements were 0.71 ± 0.17 mm, 0.72 ± 0.17 mm, 0.67 ± 0.12 mm; 0.25 ± 0.12 mm, 0.27 ± 0.14 mm, 0.25 ± 0.11 mm; and 0.43 ± 0.10 mm, 0.44 ± 0.13 mm, and 0.42 ± 0.10 mm, respectively. There was overall no significant difference between the manual and the automated IMC, ML, and IL segmentation measurements. Therefore, the automated segmentation method proposed in this study may be used successfully in the measurement of the MLT and ILT complementing the manual measurements. MLT was also shown to increase with age (for both the manual and the automated measurements). Future research will incorporate the extraction of texture features from the segmented ML and IL bands, which may indicate the risk of future cardiovascular events. However, more work is needed for validating the proposed technique in a larger sample of subjects.     

高频超声对糖尿病患者颈动脉功能改变的评价

为研究应用高频超声研究糖尿病患者颈动脉功能的改变,应用高频超声对65例2型糖尿病患者（分糖尿病无高血压组n=30和糖尿病合并高血压组n=35）以及40例健康人进行颈动脉的二维超声检测,记录颈动脉内中膜厚度（IMT）;应用M_型超声记录颈总动脉前后壁在收缩期和舒张期的运动幅度变化,测量收缩期和舒张期的内径,计算僵硬度指数口、扩张性（distensibility）和顺应性（compliance）,经心率和脉压矫正后的前壁加速度（ACi）、减速度（DCi）等参数。发现两组糖尿病患者IMT、僵硬度指数明显高于正常对照组（P〈0.01,扩张性和顺应性降低（P〈0.01,加速度和减速度降低（P〈0.01,且糖尿病合并高血压组IMT和僵硬度指数明显高于糖尿病无高血压组,扩张性和顺应性及加速度和减速度明显低于糖尿病无高血压组。IMT与年龄、僵硬度指数、扩张性和顺应性及加速度和减速度间有相关性。高频超声对评价糖尿病患者颈动脉血管功能变化有重要的实用价值。     

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy‐one chronic HD patients and 65 age‐ and sex‐matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high‐performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.     

Effects of enoxaparin on myeloperoxidase release during hemodialysis

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin‐binding protein. We studied if low‐molecular‐weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin‐grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin‐anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6‐fold at 10 minutes and 3.3‐fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin‐free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose‐dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.     

Positive association between plasma levels of oxidized low‐density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end‐stage renal disease

End‐stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low‐density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized‐LDL (ox‐LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox‐LDL levels, plasma MPO levels, and serum high‐sensitivity C‐reactive protein (hs‐CRP) levels during initial HD in patients with diabetic ESRD. Patients (n = 28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox‐LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme‐linked immunosorbent assay kit. Plasma ox‐LDL levels and MPO levels after a single HD session increased significantly (ox‐LDL, P < 0.005; MPO, P < 0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre‐HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox‐LDL levels during HD (R = 0.62, P = 0.0029). No significant change was observed in serum hs‐CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox‐LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox‐LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.     

Uremic hyperhomocysteinemia: a randomized trial of folate treatment for the prevention of cardiovascular events

Homocysteine is a risk factor for atherosclerosis in the general population, and serum homocysteine levels are almost universally elevated in chronic renal failure patients. When such patients are treated with dialysis, cardiovascular disease accounts for more than 50% of their mortality, which, in some proportion, may be pathophysiologically related to the elevated serum homocysteine levels. From April 2003 to March 2005, we conducted a 2-year, double-blind, randomized, placebo-controlled trial of 186 patients with end-stage kidney disease due to any cause, who were older than 18 years and stable on hemodialysis. Patients were assigned to receive either oral folic acid 10 mg 3 times a week immediately after every dialysis session under nurse supervision or an identical-appearing placebo for the entire study. On admission, plasma total homocysteine (tHcy) levels were above 13.9 micromol/L in 96.7% of patients (median 25.0 micromol/L, range 9.3-104.0 micromol/L). In the placebo group, tHcy levels remained elevated at 6, 12, and 24 months, while oral folate significantly decreased tHcy to a median value of 10.5 (2.8-20.3) micromol/L, (p<0.01). During the study, 38 patients (folic acid group 17 vs. placebo group 21; p=0.47) died from cardiovascular disease. Kaplan-Meier life table analysis dealing with the incidence of cardiovascular events, both fatal and nonfatal (myocardial infarction, arrhythmias, angina, heart failure, cerebrovascular accident), showed that 2 years of folic acid treatment and the lowering of the homocysteine blood levels had no effect on cardiovascular events (p=0.41; hazard ratio 1.24, 95% CI 0.74-2.10). However, the carotid artery intima-media wall thickness measured in a blinded fashion decreased from 1.94 +/- 0.59 mm to 1.67 +/- 0.38 mm (p<0.01) after 2 years of folate therapy. In this short-term study of uremic patients, 2 years of folic acid supplementation normalized the tHcy blood levels in 92.3% of patients but did not change the incidence of cardiovascular events compared with the control group. However, ultrasonography of the common carotid arteries performed at entry and 24 months later showed a significant decrease in intima-media thickness with folate supplementation. This suggests that early folate supplementation may benefit patients with chronic renal failure by preventing cardiovascular deterioration.     

Changes of Plasma Amino Acid Profile in Hemodialysis Patients

Background:  The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP, and interleukin-6 (IL-6) in HD patients.
Methods:  The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who were treated by on standard HD for at least 6 months. The patients were divided in two groups, depending on the presence (HCV+) or absence (HCV–) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured, and the values were compared with 22 healthy controls.
Results:  The median of hsCRP, IL-6, and the hsCRP/IL-6 ratio were: 3.5 vs. 2.1 mg/L, p < 0.05; 4.3 vs. 0.9 pg/mL, p < 0.0001; and 0.8 vs. 2.7 pg/mL, p < 0.0001 for patients and controls, respectively. Age, gender, S-Alb, IL-6, and hsCRP did not differ between the HCV+ and HCV– patients. However, HCV+ patients had higher ALT (29 ± 21 vs. 21 ± 25 UI/L) and had been a longer time on HD (6.1 ± 3.0 vs. 4.0 ± 2.0 years) (p < 0.0001), respectively. Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs. 0.9; p < 0.05) as compared to the HCV group.
Conclusion:  The finding that the hsCRP/IL-6 ratio was lower in HCV+ patients than in HCV– patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP may be required to define inflammation in HD patients.     

Implantable cardioverter defibrillator in maintenance hemodialysis patients with ventricular tachyarrhythmias: A single-center experience

Patients with hemodialysis (HD) are at risk of death due to cardiac arrhythmias, worsening congestive heart failure (CHF), and noncardiac causes. This study reviews our experience with the use of implantable cardioverter defibrillators (ICDs) in patients with ventricular tachycardia who are under maintenance HD. We retrospectively reviewed 71 consecutive patients who underwent an ICD implantation in our hospital. There were 11 patients under maintenance HD and 60 patients without HD. The group of patients with HD (HD group) was compared with the patients without HD (control group). The mean follow-up period was 30±9 vs. 39±4 months in the HD group vs. the control group, respectively. Among these patients, 6 in the HD group and 26 in the control group received appropriate ICD therapies. There was no difference in appropriate ICD therapy, time to the first therapy, and electrical storm between the 2 groups. In the HD group, 1 patient underwent surgical removal of the ICD system due to infective endocarditis. There were 5 deaths in the HD group (4 from CHF) and 8 deaths in the control group (4 from CHF). There were no sudden cardiac deaths or arrhythmic deaths in both groups of patients during the follow-up period. However, the overall death rate was significantly higher in the HD group (P<0.01). In HD patients, ICD therapy prevented arrhythmic death, but their rate of nonarrhythmic adverse outcomes was high. This risk-benefit association should be considered before implantation of the device.