Ultrasensitive assay for detection of serum paraoxonase by modulating the growth of fluorescent semiconductor nanoparticles

Serum paraoxonase (PON1) is an enzyme associated exclusively with high-density lipoproteins and seems to be an antiatherogenic agent that prevents initiation and progression of atherosclerosis. PON1 also hydrolyzes organophosphates, protecting the nervous system from those neurotoxic compounds. Furthermore, PON1 could be a potential indicator for predicting and preventing other diseases, such as coronary artery disease, different kinds of cancers, diabetes mellitus type 2, metabolic syndrome, neurological disorders, liver disorders, etc. Here we report an ultrasensitive assay to measure PON1 arylesterase activity relying on the enzymatic modulation of the growth of fluorescent CdS nanoparticles (NP). The lowest PON1 activity that could be detected by our system was 0.625 mU mL(-1), with a dynamic range up to 5 mU mL(-1). This new system leads to an improvement of the limit of detection by around 15 times, compared to the conventional assays to determine PON1 arylesterase activity. This new system was also applied to determine PON1 arylesterase activity in human serum by the standard addition method. Furthermore, experiments with diluted serum spiked with PON1 demonstrated recovery of PON1 activity near 100%.     

Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.     

Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched‐cohort and population‐based study in Taiwan

The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population‐based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow‐up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26–4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03–1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09–4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD.     

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.     

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.     

Paraoxonase 1-bound magnetic nanoparticles: preparation and characterizations

This is most probably the first time that covalently binding of Human serum paraoxonase 1 (PON1) to superparamagnetic magnetite nanoparticles via carbodiimide activation was investigated and presented in this study. PON1 was purified from human serum using ammonium sulfate precipitation and hydrophobic interaction chromatography (Sepharose 4B, L-tyrosine, 1-Napthylamine) and magnetic iron oxide nanoparticles were prepared by co-precipitation Fe(+2) and Fe(+3) ions in an ammonia solution at room temperature. X-ray diffraction (XRD) and the magnetic measurements showed that the nanoparticles are magnetite and superparamagnetic, respectively. Direct measurements by dynamic light scattering revealed that the hydrodynamic size was 16.76 nm with polydispersity index (PDI: 0.234). The analysis of Fourier transform infrared spectroscopy revealed that the PON1 was properly bound to magnetic nanoparticles replacing the characteristic band of -NH2 at 1629 cm(-1) with the protein characteristic band at 1744 cm(-1) and 1712 cm(-1). Magnetic measurements determined that PON1-bound nanoparticles have also favorable superparamagnetic properties with zero coercivity and remanence though a slightly smaller saturation magnetization due to the decrease of magnetic moment in the volume friction. The kinetic measurements indicated the PON1-bound nanoparticles retained 70% of its original activity and exhibited an improved stability than did the free enzyme. The PON1 enzyme is seen to be quite convenient to bind superparamagnetic nanoparticles as support material.     

Role of turmeric in oxidative modulation in end‐stage renal disease patients

Oxidative stress is considered as a major player in uremia‐associated morbidity and mortality in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of turmeric on oxidative stress markers in HD patients. This study was a prospective and double‐blind randomized clinical trial. Fifty HD patients aged 18–60 years were recruited after fulfilling the inclusion criteria. Patients were randomly categorized into 2 groups: trial group received turmeric and control group received placebo for 8 weeks. Each patient in the trial group received turmeric, whereas the control group received starch for the same 8 weeks. Plasma malondialdehyde (MDA), red blood cell (RBC) antioxidant enzyme activities as glutathione peroxidase (GPX), glutathione reductase (GR), and catalase (CAT), cholesterol, high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol, triglyceride, albumin, and hemoglobin were also measured before and after study. Although MDA level was reduced in both groups, the ratio of decrease was significantly higher in the turmeric group (0.2 vs. 0.1, P = 0.040). Three enzymes of GPX, GR, and CAT levels were increased in both groups; the ratio of increased was significantly higher in the turmeric group for the CAT enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in the turmeric group compared with the control group was observed (P = 0.001). Regular ingestion of turmeric reduces plasma MDA and increases RBC CAT activity and plasma albumin levels in HD patients. Turmeric showed no adverse effects.     

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.     

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients

Introduction: 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. Methods: 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. Findings: 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. Discussion: 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.     

Cirrhosis Ameliorates Renal Osteodystrophy in Patients on Regular Hemodialysis

Cirrhosis (Cir) is often associated with chronic renal failure (CRF) in Egyptian patients on regular hemodialysis (RHD). This is largely attributed to hepatosplenic schistosomiasis and concomitant Hepatitis C viral infection. As the liver has a major role in vitamin D3 activation, we designed this study to envisage the impact of Cir on renal osteodystrophy (ROD). It included 130 consecutive age‐ and gender‐matched subjects in 4 categories. Group I: 39 patients (34 male and 5 female; mean age 48.8 years) with Cir normal renal function; group II: 37 patients (30 male and 7 female; mean age 49.0 years) with CRF and normal liver function, on RHD for a mean duration of 6 ± 3.9 years; group III: 41 patients (30 male and 11 female; mean age 50.7 years) with CRF and concomitant Cir, stable on RHD for a mean duration of 7.0 ± 4.0 years; and group IV: 16 normal volunteers (13 male and 3 female; mean age 46.3 years). The prevalence of diabetes as well as previous infection with schistosomiasis was similar in all patient groups and that of HCV infection was alike in groups I and III. In all subjects, conventional parameters of liver and renal function were tested; in addition to measurement of serum total protein, albumin, calcium, phosphate, total and bone‐specific alkaline phosphatase (B‐ALP), parathormone (PTH), 5‐hydroxycholecalciferol (5HD), 1,25‐dihydroxycholecalciferol (1,25HD), Cross Laps (CXL) as a marker of bone resorption, and aminoterminal propeptide of type I procollagen (PINP) as a measure of bone formation. Bone mineral density (BMD) was measured by either Dual Energy X‐ray Absorptiometry (DEXA) or Computerized Tomography (CT). Group II patients displayed the typical CRF profile comprising hypocalcemia, hyperphosphatemia, increased total and bone‐specific alkaline phosphatases, high PTH and 25HD, low 1,25HD, increased PINP as well as CXL, and generally decreased BMD. Cir (Group III) significantly (p value at least <0.5) modified this profile in several aspects: it checked hypocalcemia (mean 8.8 vs. 7.9 mg/dL in groups II and III, respectively), hyperphosphatemia (5.15 vs. 4.9 mg/dL), and the elevation of B‐ALP (62 vs. 30.5 μg/L) and PTH (89 vs. 78 pg/mL). It lowered the serum level of 25HD (18.7 vs. 13.7 ng/mL), augmented the deficiency of 1,25HD (13.4 vs. 8.0 pg/mL), did not appreciably affect the increase in bone formation (PINP 77.9 vs. 75.5 ng/mL), but ameliorated its excessive resorption (CXL 21 860 vs. 30 328 pmol/L) noticed in group II. This was associated with amelioration of the dialysis‐associated osteopenia (70 vs. 33.5%) and increased incidence of osteosclerosis (30 vs. 61%), as measured by bone mineral density. Conclusion: Our data indicate that Cir ameliorates ROD through decreased bone resorption. This is associated with better tolerance to 1,25HD deficiency, which initiates the cascade of hypocalcemia, hyperparathyroidism, and increased bone resorption in CRF. Such tolerance may reflect upregulation of vitamin D receptors as a consequence of the humoral perturbation supervening in Cir, involving IGF‐1, estrogens, or other vitamin D metabolites as 24,25 HD.     

Neither oxidized nor anti-oxidized low-density lipoprotein level is associated with atherosclerosis or mortality in hemodialysis patients

It is anticipated that oxidized low‐density lipoprotein (oxLDL) and anti‐oxLDL are associated with atherosclerosis and mortality. However, data on this issue are controversial and limited. We aimed to investigate the effect of these two markers on the extent and progression of atherosclerosis and mortality in a group of hemodialysis patients. In this prospective observational study with a follow‐up of 36 months, 124 hemodialysis patients were studied. Ninety‐five patients underwent carotid intima media thickness (CA‐IMT) measurement by B‐Mode ultrasonography both at baseline and at the end of the study. oxLDL and anti‐oxLDL were measured by enzyme‐linked immunosorbent assay. The extent and progression of CA‐IMT, along with overall and cardiovascular mortality, were assessed. The mean age at baseline was 54.0 ± 14.8 years, 57.3% male and 20% diabetic. The mean oxLDL and anti‐oxLDL levels were 8.11 ± 3.16 mU/L and 1.30 ± 0.31, respectively. Baseline mean CA‐IMT was 0.82 ± 0.20 mm. Fifteen patients died during a follow‐up period of 28.5 ± 6.6 months, 11 from cardiovascular causes. Only oxLDL, not anti‐oxLDL, was correlated with the extent of atherosclerosis at baseline. However, both had no role in the progression of atherosclerosis. Also, in unadjusted and adjusted models, both parameters were not associated with overall or cardiovascular mortality. Neither oxLDL nor anti‐oxLDL level is associated with the progression of atherosclerosis or mortality in hemodialysis 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.     

Genetic polymorphisms and the risk of progressive renal failure in elderly Hungarian patients

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end‐stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T‐786C, endothelin‐1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase‐1 Q192R and M55L, angiotensinogen M235T, angiotensin‐converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real‐time polymerase chain reaction with melting‐point analysis, and two via allele‐specific amplification and gel electrophoresis. Control group patients were in Hardy‐Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis‐dependent ESRD.     

Oxidized low‐density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: Influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene

Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low‐density lipoprotein (ox‐LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox‐LDL and adiponectin were measured using enzyme‐linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox‐LDL/low‐density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A‐I, apo B, ox‐LDL, and TC/high‐density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox‐LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).     

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.     

Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities

Inflammation and lipid abnormalities are two important risk factors for cardiovascular disease in hemodialysis (HD) patients. The present study was designed to investigate the effects of flaxseed consumption on systemic inflammation and serum lipid profile in HD patients with lipid abnormalities. This was an unblinded, randomized clinical trial. Thirty HD patients with dyslipidemia (triglyceride >200 mg/dL and/or high‐density lipoprotein‐cholesterol (HDL‐C) <40 mg/dL) were randomly assigned to either a flaxseed or control group. Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks, whereas patients in the control group received their usual diet, without any flaxseed. At baseline and at the end of week 8, 7 mL of blood was collected after a 12‐ to 14‐hour fast and serum concentrations of triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol (LDL‐C), HDL‐C, and C‐reactive protein (CRP) were measured. Serum concentrations of triglyceride (P < 0.01), total cholesterol (P < 0.01), LDL‐C (P < 0.01), and CRP (P < 0.05) decreased significantly in the flaxseed group at the end of week 8 compared with baseline, whereas serum HDL‐C showed a significant increase (P < 0.01). These changes in the flaxseed group were significant in comparison with the control group. The study indicates that flaxseed consumption improves lipid abnormalities and reduces systemic inflammation in HD patients with lipid abnormalities.     

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.     

The effect of zinc deficiency on salt taste acuity,preference, and dietary sodium intake in hemodialysis patients

Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross‐sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3‐day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non‐zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non‐zinc deficient group (2.68 ± 1.02 kg vs. 3.18 ± 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.     

Effects of music on complications during hemodialysis for chronic renal failure patients

The study was planned as a case‐control study to examine the effects of music on some of the complications experienced by chronic renal failure (CRF) patients during hemodialysis. A total of 60 patients (30 intervention and 30 control) diagnosed with end‐stage renal failure undergoing hemodialysis treatment participated in this study. The study was conducted in Manisa Merkez Efendi State Hospital Hemodialysis Unit and Manisa Özel Anemon Hemodialysis between April 2012 and July 2012. The intervention group listened 30 minutes in each session (12 total sessions) Turkish art music at the beginning of the third hour of their hemodialysis sessions. Patient Information Form and visual analog scale to assess pain, nausea, vomiting, and cramps during hemodialysis session were used. For the analysis of data, the number, percentage, chi‐square test, and significance test of independent group differences between two averages were conducted. According to the findings of the study, the average of the intervention and control group ages, respectively, was 50.86 ± 11.3 and 55.13 ± 9.68. The primary duration of hemodialysis treatment for both intervention and control groups was “1 year and above” (70.0%). The intervention group's pain and nausea scores were lower than the control group for all 12 sessions. The difference between the intervention and the control group's pain scores was significant (P < 0.05). However, in pain scores from the first session to 12th session, continuous decreasing trend was not observed. According to the results, music can be used as an independent nursing practice for reduction of complications for CRF patients receiving hemodialysis treatment.     

Neutrophil and monocyte activation in chronic kidney disease patients under hemodialysis and its relationship with resistance to recombinant human erythropoietin and to the hemodialysis procedure

The aim of the present work was to further clarify leukocyte activation due to hemodialysis (HD) procedures and to investigate its relationship with recombinant human erythropoietin resistance. Therefore, we studied the expression of CXCR1 and CD11b on neutrophils, as well as the monocyte expression of CD11b, HLA‐DR, and CD14. We studied 34 chronic kidney disease (CKD) patients under HD and recombinant human erythropoietin treatment (26 responders and 8 nonresponders to recombinant human erythropoietin therapy). All CKD patients' blood samples were collected before and immediately after the HD procedure. Eighteen healthy individuals (blood donors) were also studied as a control group. Hematological data, neutrophil (CD11b and CXCR1), and monocyte (CD11b, HLA‐DR, and CD14) cell surface markers were measured in all patients (before and after the HD procedure) and controls. When compared with the controls, CKD patients presented a significant decrease in CXCR1 neutrophil expression, and in CD14 monocyte expression, accompanied by a significant increase in HLA‐DR monocyte expression. When comparing the 2 groups of patients, we found that nonresponders showed an additional decrease in CXCR1 neutrophil expression. After the HD procedure, a statistically significant increase in CD14 and CD11b monocyte surface markers and a decrease in CXCR1 neutrophil expression and in HLA‐DR monocyte expression was found. These data further strengthen our previous studies, showing that neutrophils and monocytes are activated in CKD patients, particularly in nonresponder patients. Moreover, this activation is due, at least in part, to the HD procedure, although we should not exclude that it can also be due to the enhanced inflammatory process observed in nonresponder patients.