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 factors for progression of aortic arch calcification in patients on maintenance hemodialysis and peritoneal dialysis

Vascular calcification is accelerated during dialysis and is known to be an important risk factor for cardiovascular disease. Progression of aortic arch calcification (AoAC) can be simply estimated with an AoAC score (AoACS) using plain chest radiography. The objective of this study was to evaluate risk factors for AoAC progression. The enrolled subjects were 125 newly treated hemodialysis patients and 59 peritoneal dialysis patients. In the patients who had undergone chest radiography before initial dialysis therapy and every year, we estimated AoACS and then divided the patients into two groups based on the presence or absence of AoAC progression. We also compared the baseline clinical and biochemical profiles in the two groups. Eighty‐five (46.2%) were men (mean age, 58.6 ± 12.7 years). Seventy‐six patients (41.3%) had AoAC before initial dialysis, with a mean AoACS of 13.0 ± 20.4%. The mean duration of follow‐up was 2.7 ± 1.0 years. Half of the patients (50%) had progressive AoAC. Age >65 years (p = 0.003), dialysis duration (p = 0.004), diabetes (p = 0.015), and the presence of AoAC at baseline (p = 0.001) were related to AoAC progression. No significant association was found between AoAC progression and the baseline clinical parameters, including gender, obesity, hypertension, and dialysis modality. In a multivariate analysis, dialysis duration (p = 0.003) and the presence of AoAC at baseline (p < 0.001) were independent risk factors for AoAC progression in patients undergoing dialysis. The duration of dialysis and the presence of AoAC before initial dialysis were significantly related to the progression of AoAC in these patients. The results suggest that patients should be carefully managed from the predialysis stage to prevent AoAC progression and to reduce cardiovascular morbidity.     

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.     

Impact of arterial microcalcification of the vascular access on cardiovascular mortality in hemodialysis patients

Gross vascular calcification seen on imaging studies is common in hemodialysis (HD) patients, and is a significant predictor for cardiovascular mortality in HD patients. We have reported that arterial microcalcification (AMiC) of the vascular access is associated with increased aortic stiffness. This study investigated the impact of vascular access AMiC on cardiovascular mortality in HD patients. The study included 149 HD patients (mean age: 59.1 ± 13.9 years, 86 men and 63 women, 65.8% diabetic) who underwent vascular access surgery. Radial or brachial artery specimens were obtained intraoperatively, and pathologic examination was performed using von Kossa stain to identify AMiC. We compared all‐cause and cardiovascular mortality between patients with and without AMiC. The mean follow‐up was 37.8 ± 34.5 months, and AMiC was present in 38.8% (n = 57) of patients. The presence of diabetes (odds ratio: 16.49, 95% confidence interval: 1.81–150.36, P = 0.013) was the only independent risk factor for vascular access AMiC. During the observational period, there were 27 cardiovascular deaths. Kaplan–Meier analysis showed an increased cardiovascular mortality risk (log rank = 4.83, P = 0.028) in AMiC patients, and Cox regression analysis confirmed that AMiC was an independent predictor for cardiovascular mortality (hazard ratio: 2.35, 95% confidence interval: 1.09–5.09, P = 0.030). In conclusion, vascular access AMiC is a strong risk factor for cardiovascular mortality in HD patients.     

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.     

Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1–21.2 years) receiving hemodialysis for ≥2 months. Inflammation was assessed by serum IL‐6, IL‐8, and C‐reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time‐averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice‐weekly; mean single pool Kt/V 1.48±0.13; and mean normalized protein catabolic rate 1.27±0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1±2.1 vs. 15.4±3.1 months; P=0.03), had longer dialysis vintage (49.4±15.3 vs. 17.2±10.5 months, P=0.0002), lower serum cholesterol (122±17.7 vs. 160.4±10.6 mg/dL, P=0.02), and higher phosphorus (9.05±1.2 vs. 6.1±0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL‐6 and IL‐8 levels compared with healthy norms; the mean IL‐6, IL‐8, and C‐reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.     

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Atherosclerotic cardiovascular disease is an important cause of mortality and morbidity in hemodialysis patients. Iron accumulation in arterial wall macrophages is increased in atherosclerotic lesions. Hepcidin is a key hepatic hormone regulating iron balance. It inhibits iron release from macrophages and iron absorption from enterocytes by binding and inactivating the cellular iron exporter ferroportin. The aim of this study is to investigate the relation of hepcidin‐25, iron parameters, and atherosclerosis measured by carotid intima media thickness (CIMT) in hemodialysis patients. Eighty‐two hemodialysis patients were enrolled in this cross‐sectional study. Predialysis blood samples were centrifuged at 1500 g and 4°C for 10 minutes and stored at ?80°C for the measurement of hepcidin‐25. DRG hepcidin enzyme‐linked immunosorbent assay kit was used for the measurement of hepcidin‐25. Ultrasonographical B‐mode imaging of bilateral carotid arteries was performed with a high‐resolution real‐time ultrasonography (Mindray DC7). Mean age of the study population was 57.90 ± 16.08 years and 43.9% were men. Total study population was grouped into two according to median value of hepcidin‐25. There was no difference between groups with respect to age, dialysis vintage, and C‐reactive protein. CIMT was found to be statistically significantly higher in low hepcidin‐25 group. In correlation analysis, CIMT was found to be correlated with age (P < 0.01, R = 0.33) and hepcidin‐25 (P < 0.01, R = 0.46). In linear regression analysis, age (β = 0.31) and hepcidin‐25 (β = 0.44) were found to be the determinants of CIMT in hemodialysis patients. Our results implicate that hepcidin may take part in pathophysiology of atherosclerosis and cardiovascular disease in hemodialysis patients.     

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross‐sectional, 1‐year,retrospective cohort study

Introduction This study aimed to evaluate the association between proton pump inhibitor (PPI) use and serum magnesium levels, and the role of hypomagnesemia and PPI use as a risk factor for mortality in hemodialysis patients. Methods An observational study, including a cross‐sectional and 1‐year retrospective cohort study. The study comprised 399 hemodialysis patients at a single center, and was conducted from January to September 2014. Multiple linear regression analysis was used to investigate the independent relationship between serum magnesium levels and baseline demographic and clinical variables, including PPI and histamine‐2 receptor antagonist use. Cox regression model was used to identify lower serum magnesium level and PPI as a predictor of 1‐year mortality. Findings Serum magnesium levels were lower with PPI use than non‐PPI use (2.39 ± 0.36 vs. 2.56 ± 0.39 mg/dL, P < 0.001). Multiple linear regression analysis showed that PPI use, low serum albumin levels, and low serum potassium and high‐sensitivity C‐reactive protein (hs‐CRP) levels were significantly associated with low serum magnesium levels. A total of 29 deaths occurred during the follow‐up period. According to Cox regression analysis stratified by hs‐CRP, only high serum hs‐CRP levels (>4.04 mg/L) in association with low serum magnesium levels was an independent risk factor for 1‐year mortality (hazard ratio: 2.92; 95% CI: 1.53–6.40, P < 0.001). Discussion Serum magnesium levels are lower in PPI use. In the inflammatory state, a low serum magnesium level is a significant predictor of mortality in hemodialysis patients.     

Integration of clinical and imaging data to predict death in hemodialysis patients

In a prior publication, we demonstrated that a model integrating clinical and simple imaging data predicted the presence and severity of coronary artery calcification in prevalent hemodialysis patients. Herein we report the ability of the same model to predict all‐cause death. We assessed all‐cause mortality in 141 consecutive maintenance hemodialysis patients from two dialysis centers followed for a median of 79 months from enrollment. Patients were risk stratified according to a simple cardiovascular calcification index (CCI) that included patient's age, dialysis vintage, calcification of the cardiac valves, and abdominal aorta. The mean patients’ age was 55 ± 14 years. Abdominal aorta calcification was present in 57% of the patients, and 44% and 38% had aortic and mitral valve calcification, respectively. During follow‐up, 75 deaths (93 deaths per 1000 person‐years) were recorded. The CCI was linearly associated with risk of death, such that the unadjusted hazard risk (HR) increased by 12% for each point increase in CCI (P < 0.001). Further adjustments for age, sex, study center, diabetes mellitus, history of cardiovascular disease, hypertension, congestive heart failure, left ventricular hypertrophy, systolic, and diastolic blood pressure did not substantially change the strength of this association (HR 1.10; 95%CI: 1.00–1.21; P = 0.03). The CCI is a simple clinical model that can be used to risk stratify maintenance hemodialysis patients.     

Nutritional education for management of osteodystrophy: Impact on serum phosphorus,quality of life,and malnutrition

Introduction Osteodystrophy management includes dietary phosphorus restriction, which may limit protein intake, exacerbate malnutrition‐inflammation syndrome and mortality among hemodialysis patients. Methods A multicenter randomized controlled trial was conducted in Lebanon, to test the hypothesis that intensive nutrition education focused on phosphorus‐to‐protein balance will improve patient outcomes. Six hemodialysis units were randomly assigned to the trained hospital dietitian (THD) protocol (210 patients). Six others (184 patients) were divided equally according to the patients’ dialysis shifts and assigned to Dedicated Dietitian (DD) and Control protocols. Patients in the THD group received nutrition education from hospital dietitians who were trained by the study team on renal dietetics, but had limited time for hemodialysis patients. Patients in the DD group received individualized nutritional education on dietary phosphorus and protein management for 6 months (2‐hour/patient/month) from study renal dietitians. Patients in the control group continued receiving routine care from hospital dietitians who had limited time for these patients and were blinded to the study. Serum phosphorus (mmol/L), malnutrition‐inflammation score (MIS), health‐related quality of life (HRQOL) index and length of hospital stay (LOS) were assessed at T0 (baseline), T1 (postintervention) and T2 (post6 month follow up). Findings Only the DD protocol significantly improved serum phosphorus (T0:1.78 ± 0.5, T1:1.63 ± 0.46, T2:1.69 ± 0.53), 3 domains of the HRQOL and maintained MIS at T1, but this protective effect resolved at T2. The LOS significantly dropped for all groups. Discussion The presence of competent renal dietitians fully dedicated to hemodialysis units was superior over the other protocols in temporarily improving patient outcomes.     

Hemodialysis decreases carotid‐brachial and carotid‐femoral pulse wave velocities: A 5‐year follow‐up study

Aortic stiffness is a prognostic parameter associated with patient mortality. Vascular access creation has been shown to have effects on arterial stiffness both in the aorta and in the upper limb arteries in chronically hemodialyzed patients (CHPs). However, no longitudinal studies have been conducted in order to characterize the evolution of arterial stiffness in CHPs. The aims of this work were (a) to measure baseline pulse wave velocity (PWV) in the carotid‐femoral and in right and left carotid‐brachial pathways in a cohort of CHP and (b) to conduct a 5‐year prospective study on the same cohort to determine possible time‐related differences. Pulse wave velocity was measured both in the carotid‐femoral and in the carotid‐brachial pathways, and clinical and biochemical parameters were collected in 25 CHPs, which were followed up after a 5‐year lapse. Right and left carotid‐brachial pathway PWV values showed significant decreases after the 5‐year follow‐up, independently of the presence of the vascular access (P < 0.001). Additionally, baseline carotid‐brachial PWV was significantly higher (P < 0.001) than values measured 5 years later for upper limbs with vascular access (11.97 ± 2.97 m/sec vs. 6.76 ± 1.48 m/sec, respectively) and without vascular access (12.25 ± 2.38 m/sec vs. 7.18 ± 1.88 m/sec, respectively). Similarly, PWV values in the carotid‐femoral pathway decreased significantly (P < 0.001) over the same period (13.27 ± 2.96 m/sec vs. 9.75 ± 2.99 m/sec, respectively). The 5‐year follow‐up of PWV showed significant decreases in both carotid‐brachial and carotid‐femoral pathways. The general changes in arterial stiffness could be related to the vascular access creation, hemodialysis therapy, and to the improvement of arterial pressure management.     

Association of coronary artery calcium score and vascular dysfunction in long‐term hemodialysis patients

Long‐term hemodialysis patients are prone to an exceptionally high burden of cardiovascular disease and mortality. The novel temperature‐based technology of digital thermal monitoring (DTM) of vascular reactivity appears associated with the severity of coronary artery disease in asymptomatic population. We hypothesized that in hemodialysis patients, the DTM and coronary artery calcium (CAC) score have a gradient association that follows that of subjects without kidney disease. We examined the cross‐sectional DTM‐CAC associations in a group of long‐term hemodialysis patients, and their 1:1 matched normal counterpart. Area under the curve for temperature (TMP‐AUC), the surrogate of the DTM index of vascular function, was assessed after a 5‐minute arm‐cuff reactive hyperemia test. Coronary calcium score was measured via electron beam computed tomography or multidetector computed tomography scan. We studied 105 randomly recruited hemodialysis patients (age: 58 ± 13 years, 47% men) and 105 age‐ and gender‐matched controls. In hemodialysis patients vs. controls, TMP‐AUC was significantly worse (114 ± 72 vs. 143 ± 80, P = 0.001) and CAC score was higher (525 ± 425 vs. 240 ± 332, P < 0.001). Hemodialysis patients were 14 times more likely to have CAC score >1000 as compared with controls. After adjustment for known confounders, the relative risk for case vs. control for each standard deviation decrease in TMP‐AUC was 1.46 (95% confidence interval: 1.12–1.93, P = 0.007). Vascular reactivity measured via the novel DTM technology is incrementally worse across CAC scores in hemodialysis patients, in whom both measures are even worse than their age‐ and gender‐matched controls. The DTM technology may offer a convenient and radiation‐free approach to risk‐stratify hemodialysis patients.     

Left ventricular mass index and aortic arch calcification score are independent mortality predictors of maintenance hemodialysis patients

To analyze predictive factors for all‐cause mortality, cardiovascular (CV) mortality, nonfatal CV events (CVE) in maintenance hemodialysis (MHD) patients, and to compare the effects of standard hemodialysis (HD) and online hemodiafiltration (HDF) on these factors and outcomes. A total of 333 MHD patients were prospectively followed up for 50 ± 15 months and all‐cause death, CV death and CVE were registered. At the baseline, demographic, clinical, and laboratory data of the whole population were recorded. Then, patients were stratified into two groups according to the dialysis modalities, HD (n = 268) and HDF (n = 65). At the end of 6th month, clinical and laboratory data were recorded again. The predictive factors at baseline for all‐cause mortality, CV mortality, and CVE were analyzed by Cox regression. The effects of HD and HDF on these factors at the 6th month and long‐term outcomes were compared by t‐test and Kaplan–Meier method, respectively. Age, gender, left ventricular mass index (LVMI), aortic arch calcification score (AoACS), hemoglobin (Hb) <10 g/dL, and ferritin >500 ng/mL maintained independent associations with all‐cause mortality. C‐reactive protein (CRP), LVMI, AoACS, and Hb <10 g/dL were associated with CV mortality. Prior cardiovascular disease (CVD), AoACS and LVMI were independent predictors of nonfatal CVE. Higher body mass index (BMI), body weight, total serum cholesterol, Hb concentration, and lower CRP level, LVMI, and AoACS were found in patients on HDF at the end of the 6th month. Improved outcomes with longer survival time for all‐cause mortality, CV mortality, and CVE were found in HDF group. Age, gender, LVMI, AoACS, Hb, and ferritin were predictors of all‐cause mortality in MHD patients. CRP, LVMI, AoACS, and Hb were associated with CV mortality. Prior CVD, AoACS, and LVMI were independent predictors of nonfatal CVE. HDF could improve BMI, body weight, total serum cholesterol, Hb, CRP, LVMI, AoACS, and long‐term outcomes, including all‐cause mortality, CV mortality, and CVE.     

Myocardial contractile function and intradialytic hypotension

Dialysis‐induced hypotension remains a significant problem in hemodialysis (HD) patients. Numerous factors result in dysregulation of blood pressure control and impaired myocardial reserve in response to HD‐induced cardiovascular stress. Episodic intradialytic hypotension may be involved in the pathogenesis of evolving myocardial injury. We performed an initial pilot investigation of cardiovascular functional response to pharmacological cardiovascular stress in hypotension‐resistant (HR) and hypotension‐prone (HP) HD patients. We studied 10 matched chronic HD patients (5 HP, 5 HR). Dobutamine‐atropine stress (DAS) was performed on a nondialysis short interval day, with noninvasive pulse‐wave analysis using the Finometer^® to continuously measure hemodynamic variables. Baroreflex sensitivity was assessed at rest and during DAS. Baseline hemodynamic variables were not significantly different. The groups had differing hemodynamic responses to DAS. The Mean arterial pressure was unchanged in the HR group but decreased in HP patients (?13.6 ± 3.5 mmHg; P<0.001). This was associated with failure to significantly increase cardiac output in the HP group (cf. increase in cardiac output in the HR group of +33.4 ± 6%; P<0.05), and a reduced response in total peripheral resistance (HP ?10.3 ± 6.8%, HR ?22.7 ± 2.9%, P=NS). Baroreflex sensitivity was not significantly different between groups at baseline or within groups with increasing levels of DAS; however, the mean baroreflex sensitivity was higher in HR cf. HP subjects throughout pharmacological stress (P<0.05). Hypotension‐prone patients appear to have an impaired cardiovascular response to DAS. The most significant abnormality is an impaired myocardial contractile reserve. Early identification of these patients would allow utilization of therapeutic strategies to improve intradialytic tolerability, potentially abrogating aggravation of myocardial injury.     

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.     

Efficacy of losartan for improving insulin resistance and vascular remodeling in hemodialysis patients

Insulin resistance and vascular remodeling are prevalent and predict cardiovascular mortality in hemodialysis patients. Angiotensin II (Ang II) may be involved in both pathogenesis. In the present study, we investigated the effects of the Ang II receptor blocker losartan on insulin resistance, arterial stiffness, and carotid artery structure in hemodialysis patients. Seventy‐two hemodialysis patients were randomly assigned to receive either losartan 50 mg qd (n = 36) or β‐blocker bisoprolol 5 mg qd (n = 36). At the start and at month 12, ambulatory blood pressure (BP) monitoring, aortic pulse wave velocity (PWV) measurements, and carotid artery ultrasound were performed, and homeostasis model assessment index of insulin resistance (HOMA‐IR) was determined. During the study period, bioimpedance method was used to evaluate volume status every 3 months. Home‐monitored BPs were measured at least monthly. Ambulatory BP decreased significantly and similarly by either losartan or bisoprolol. Decreases in PWVs in losartan group at the end of month 12 were significantly greater than changes in PWV in bisoprolol group (0.9 ± 0.3 vs. 0.4 ± 0.5 m/s, P = 0.021). Common carotid artery intima‐media cross‐sectional area decreased significantly only in patients treated with losartan (20.3 ± 4.9 vs. 19.1 ± 5.1 mm², P = 0.001), and HOMA‐IR was also reduced in losartan group only (1.9 ± 1.0 vs. 1.7 ± 0.8, P = 0.003). Multiple regression analysis showed significant correlations between changes in PWV and changes in HOMA‐IR. With comparable BP‐lowering efficacy, losartan achieved better improvement in insulin sensitivity, arterial stiffness, and carotid artery hypertrophy in hemodialysis patients. The regression of arterial stiffness may be in part through attenuation in insulin resistance.     

Dipyridamole stress echocardiography in diagnosis and prognosis of hemodialysis patients with asymptomatic coronary disease

The prevalence of coronary artery disease (CAD) is high in hemodialysis (HD) patients. The aim of the study was to assess the diagnostic and prognostic value of dipyridamole stress echocardiography (DSE) in nondiabetic HD patients without signs or symptoms of CAD. In 51 out of 158 evaluated HD patients (21 females, age 67 [33–85] years, HD duration 38 [9–271] months), resting echocardiography and DSE were performed. Exclusion criteria were known CAD, diabetes mellitus, and pulmonary and oncologic pathologies. Logistic regression analysis was carried out to identify predictors of abnormal DSE response, while Cox regression analysis was performed to determine variables associated with total and cardiovascular mortality, after 43.3 (11–60) months of follow‐up. Seven patients (14%) showed a positive response to DSE (DSE+). In 5/7, CAD was documented by angiography: All of them underwent coronary revascularization. DSE+ patients had significantly smaller body mass index than patients with a negative response (DSE‐): 21.7 ± 1.9 vs. 25.1 ± 3.4 kg/m² (p = 0.018). During follow‐up, 16 (31%) patients died. Older age hazard ratio [HR = 1.07; confidence interval (CI) = 1.01–1.12; p = 0.02] and higher plasma phosphate levels (HR = 10.41; CI = 2.30–47.17; p < 0.01) were predictors of total mortality. Male gender (HR = 22.7; CI = 1.45–354.4; p = 0.03), older age (HR = 1.24; CI = 1.03–1.50; p = 0.02), longer HD duration (HR = 1.13; CI = 1.01–1.26; p = 0.04), and positive response to DSE (HR = 5.82; CI = 1.04–32.65; p = 0.04) were associated with cardiovascular mortality. Ten percent of asymptomatic HD patients had significant CAD, but timely diagnosis did not seem to improve their prognosis. Total survival was associated with age and higher levels of plasma phosphate, while male gender, older age, longer HD duration, and DSE+ were predictors of cardiovascular mortality.     

Impact of inflammation on anti‐oxidative effects of vitamin E‐coated membrane dialyzer in patients on chronic hemodialysis

Hemodialysis (HD) with the use of vitamin E‐coated membrane (VEM) dialyzers is shown to exert anti‐inflammatory and antioxidative effects in patients with end‐stage renal disease on HD. However, the association of baseline inflammatory status with the antioxidative effects of VEM has not been investigated thus far. Thirty‐five stable end‐stage renal disease patients treated with VEM for 6 months were enrolled in the present prospective, observational cohort study. For the previous 3 months minimum, 17 (48%) patients were dialyzed with a cellulose, eight (23%) patients with a hemophane, and 10 (29%) patients with a polysulfone 1.2 to 1.5 m² hollow fiber dialyzer. The effects of treatment on oxidized low‐density lipoprotein (oxLDL) were stratified according to half percentiles of baseline serum logC‐reactive protein and interleukin‐6, and the association between treatment goal, arbitrarily defined as a minimum 30% decrease in baseline oxLDL, was assessed with the use of logistic regression analysis. The higher C‐reactive protein and interleukin‐6 half percentiles were independently and additively associated with a higher odds ratio for achieving treatment goal. Adjustment for baseline oxLDL, age, sex, HD duration, smoking, and body mass index did not attenuate the odds ratios, whereas the history of diabetes, as primary renal disease, significantly decreased the odds ratio for achieving treatment goal. Increased baseline C‐reactive protein and interleukin‐6 are independent, additive factors associated with the effect of VEM on oxLDL in HD patients.     

Occult hepatitis B among patients with chronic renal failure on hemodialysis from a capital city in northeast Brazil

Occult hepatitis B (OHB) is characterized by the presence of HBV‐DNA in the absence of HBsAg in the serum of patients. Hemodialysis patients are at high risk for hepatitis B virus and there are few data on the prevalence of OHB in this population, mainly in Brazil. Thus, the aim of this study was to determine the prevalence of OHB in patients undergoing hemodialysis. A cross‐sectional study was performed, including 301 patients on chronic hemodialysis at two dialysis centers in São Luís (Maranhão), northeast Brazil. Serological tests were performed for HBsAg, anti‐HBc, anti‐HBs, and anti‐HCV using enzyme immunoassays (ELISA); HBV‐DNA and HCV‐RNA were studied by real‐time PCR. The mean age was 49 ± 15 years, and 128 (42%) were female. Serological tests confirmed that all samples were HBsAg negative. Anti‐HBc was positive in 114 (38%) patients, anti‐HBc and anti‐HBs were simultaneously positive in 104 (35%), and anti‐HBc alone was positive in 10 (3%). Tests were negative for anti‐HBc and anti‐HBs in 55 patients (18%). Anti‐HBs was the only positive marker in 132 (44%) patients. Anti‐HCV was positive in 15 (5%) patients with HCV‐RNA present in 14 of them (93%). HBV‐DNA was positive in seven cases (2.3%). There was no association of HBV‐DNA with age, gender, time on dialysis, previous kidney transplant, or HBV serological pattern, but there was a positive correlation with the presence of anti‐HCV (P < 0.001). OHB in chronic renal failure patients on hemodialysis appears to be a relevant finding, suggesting that studying HBV‐DNA in this population using sensitive molecular tests should be a recommended course of action, especially in candidates for renal transplant.