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.     

Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients

Fibroblast growth factor-23 (FGF-23) has been suggested to play a role in vascular calcification in chronic kidney disease. Common carotid artery intima-media thickness (CIMT) assessment and common carotid artery (CCA) plaque identification using ultrasound are well-recognized tools for identification and monitoring of atherosclerosis. The aim of this study was to test that elevated FGF-23 levels might be associated with carotid artery atherosclerosis in maintenance hemodialysis (HD) patients. In this cross-sectional study, plasma FGF-23 concentrations were measured using a C-terminal human enzyme-linked immunosorbent assay kit. Carotid artery intima-media thickness was measured and CCA plaques were identified by B-Mode Doppler ultrasound. One hundred twenty-eight maintenance HD patients (65 women and 63 men, mean age: 55.5 ± 13 years, mean HD vintage: 52 ± 10 months, all patients are on HD thrice a week) were involved. The mean CIMT were higher with increasing tertiles of plasma FGF-23 levels (0.66 ± 0.14 vs. 0.75 ± 0.05 vs. 0.86 ± 0.20 mm, P<0.0001). Log plasma FGF-23 were higher in patients with plaques in CCA than patients free of plaques (3.0 ± 0.17 vs. 2.7 ± 0.23, P<0.0001). Significant correlation was recorded between log plasma FGF-23 and CIMT (r=0,497, P=0.0001). In multiple regression analysis, a high log FGF-23 concentration was a significant independent risk factor of an increased CIMT. Further studies are needed to clarify whether an increased plasma FGF-23 level is a marker or a potential mechanism for atherosclerosis in patients with end-stage renal disease.     

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.     

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.     

Effect of vitamin D supplementation on endothelial dysfunction in hemodialysis patients

Introduction: Patients with chronic kidney disease (CKD) commonly experience 25‐hydroxyvitamin D3 (25‐OH‐D3) deficiency, and these patients have a higher incidence of cardiovascular diseases (CVDs) due to endothelial dysfunction (ED). The aim of our study was to investigate the effect of 25‐OH‐D3 deficiency and its supplementation on ED in patients with CKD. Methods: Twenty‐nine uremic patients on dialysis and 20 healthy controls were evaluated for ED by high‐resolution Doppler ultrasonography of the brachial artery. In addition, 25‐OH‐D3‐deficient patients (25‐OH‐D3 < 30 nmol/L) with CKD and healthy controls were evaluated for ED before and after 8 weeks of oral vitamin D (cholecalciferol, 50,000 units) treatment. All subjects were evaluated for percent flow‐mediated dilatation (%FMD), percent endothelium‐independent nitroglycerin‐induced vasodilatation (%NID), and bilateral carotid intima‐media thickness (CIMT). Findings: Patients on dialysis had lower %FMD and %NID 6.11 [2.27–12.74] and 10.96 [5.43–16.4], respectively, than controls 15.84 [8.19–22.49] and 21.74 [12.49–29.4], respectively (P < 0.05). Patients on dialysis had higher left and right CIMT (0.79 ± 0.15 and 0.78 ± 0.14, respectively) than controls (0.60 ± 0.09 and 0.59 ± 0.09, respectively; P < 0.05). In 25‐OH‐D3‐deficient patients with CKD, after vitamin D treatment, %FMD was significantly increased in dialysis patients (10.25 [7.8–12.8]) compared to before supplementation (5.4 [2.77–6.15]; P < 0.001). Discussion: These results indicated that dialysis patients had significantly lower blood 25‐OH‐D3 levels and higher CIMT than healthy subjects. In addition, vitamin D supplementation improved ED and increased %FMD in dialysis patients. Our findings suggest that vitamin D supplementation in dialysis patients might prevent CVD.     

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.     

Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof‐of‐concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti‐Xa activity during hemodialysis (HD) sessions using a new heparin‐grafted HD membrane. In 45 stable HD patients, the use of a heparin‐grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse‐back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti‐Xa activity by 50%. Dose reductions were achieved with both types of heparin (low‐molecular‐weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti‐Xa activity at dialysis session end (low‐molecular‐weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti‐Xa activity at the end of HD sessions was possible in stable HD patients using heparin‐grafted membrane. HD patients who require low anti‐Xa activity at the end of HD sessions might benefit from a heparin‐grafted membrane to reduce bleeding risk and other heparin adverse events.     

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.     

Endotoxins and inflammation in hemodialysis patients

Long‐term endotoxin challenge may promote frequent complications in dialysis patients, namely malnutrition, chronic inflammation, and atherosclerosis, which are recognized as the so‐called MIA syndrome. Circulating soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels may be used to determine the stage of atherosclerosis. This study aimed to assess endotoxin level in hemodialysis (HD) patients and its role in inducing inflammation. The study was conducted on 50 HD patients, chosen from four dialysis centers in Alexandria. Serum blood samples were collected for the determination of albumin and C‐reactive protein (CRP), and whole blood samples were used for the measurement of hemoglobin level. A heparinized whole blood sample was taken postdialysis for endotoxin assay by limulus amebocyte lysate test, and in addition to sVCAM‐1 was estimated using enzyme‐linked immunosorbent assay. The mean endotoxin level was 76.30 pg/mL;80% exhibited values higher than 60 pg/mL. Half the studied patients had CRP values that exceeded the upper limit of the laboratory reference range (<6.0 mg/L). A statistically significant correlation was found between endotoxin and CRP levels (r = 0.47, P = 0.001). The mean pre‐HD level of VCAM was 1851.00 ng/mL, while the mean post‐HD level was 2829.00 ng/mL with statistically significant correlation (r = 0.354, P = 0.012) and it also correlated significantly with endotoxin as well as CRP levels. Endotoxemia may play an important role in the aggravation of endothelial dysfunction in HD patients as indicated by the post‐HD rise in sVCAM‐1.     

Epicardial fat thickness is associated with impaired coronary flow reserve in hemodialysis patients

Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD) patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of this study was to evaluate the association between EFT and coronary artery flow reserve (CFR), which is an early indicator of endothelial dysfunction in coronary vessels of HD patients. We performed a cross‐sectional study including 71 chronic HD patients and 65 age‐ and sex‐matched healthy controls. Epicardial fat tissue was significantly higher in HD patients when compared to healthy controls (6.53 ± 1.01 mm vs. 5.79 ± 1.06 mm, respectively, P < 0.001). On transthoracic Doppler echocardiography, CFR values were significantly lower in HD patients when compared to healthy controls (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001). Correlation analysis showed CFR values to be inversely correlated with EFT (r = ?0.287, P < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. Artery flow reserve, age, body mass index and total cholesterol levels were independently correlated with EFT thickness. This study demonstrated that EFT was significantly higher among HD patients compared to healthy controls. In addition, this study was the first to demonstrate an inverse correlation between EFT and CFR in this patient population.     

Hemodialysis‐induced regional left ventricular systolic dysfunction

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4‐hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD‐induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD‐induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Higher cTnT (0.060 ± 0.030 vs. 0.048 ± 0.015 ng/mL, P = 0.023), phosphate (2.07 ± 0.50 vs. 1.49 ± 0.96 mmol/L, P = 0.001), UFR (11.00 ± 3.89 vs. 8.30 ± 2.66 mL/Kg/h, P = 0.039) and lower albumin (37.83 ± 4.48 vs. 38.38 ± 2.53 g/L, P = 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR = 1.047, 95%CI 1.155–4.732, P = 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate.     

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost‐efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross‐over design: high‐flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.     

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).     

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.     

Relation between Access-Related Infection and Preinfection Serum Albumin Concentration in Patients on Chronic Hemodialysis

Background: Hemodialysis (HD) access‐related infection is a major cause of morbidity and mortality in HD patients. We tested whether hypoalbuminemia is a risk factor for HD access infection and whether mortality of HD catheter infection is affected by removal of the infected catheter. Methods: We analyzed the records of 87 patients on chronic HD who were hospitalized for HD access‐related infection. We obtained data on age, sex, preinfection serum albumin level, comorbidities, complications, infecting organism, type of infection, mode of management, and mortality. We compared preinfection serum albumin levels in 79 patients with HD access infection with the serum albumin levels of 198 control patients on chronic HD without HD access infection admitted to the hospital during the same time for other reasons. In the HD catheter infection subgroup, we compared mortalities between patients treated with catheter removal plus antibiotics as the primary mode of management and those treated initially with antibiotics alone. Results: Preadmission serum albumin level was lower in the HD access infection group (2.4 ± 0.6 g/dL) than in the control group (3.2 ± 0.6 g/dL, P < 0.0001). Logistic regression identified preadmission serum albumin level as a strong independent predictor of HD access infection. In a logistic regression model, with age, sex, HIV status, diabetes, and type of HD vascular access (excluding arterovenous fistula) as the covariates, the odds ratio of HD access infection was 9.8 (95% confidence interval [CI] 4.9–19.7) for a serum albumin level ≤ 3.0 g/dL (P < 0.0001), 10.4 (95% CI 4.97–21.6) for a serum albumin level ≤ 2.5 g/dL (P < 0.0001), and 28.0 (95% CI 5.8–135.9) for a serum albumin level ≤ 2.0 g/dL (P < 0.0001). Case mortality was 25.0% (4/16) in patients with tunneled HD catheter infection initially treated with antibiotics alone and 2.8% (2/71) in those treated with catheter removal plus antibiotics at the time of presentation (P = 0.0096). Conclusion: Hypoalbuminemia is associated with increased risk of HD access infection. Treatment of HD access infection with antibiotics alone is associated with increased risk of death.     

Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patients

Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA‐IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 ± 10.6 μU/mL) was significantly lower than patients without rHuEPO (group B) (28.8 ± 7.7 μU/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 ± 2.97, 7.98 ± 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA‐IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 ± 3.2, 9.4 ± 7.2, respectively, P<0.001). Also, HOMA‐IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 ± 2.85, 6.9 ± 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=?0.62, ?0.71, and ?0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients.     

Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients

This study was performed to investigate the relationship between left atrium (LA) volume index (LAVI) and left ventricle electrical activity presumably repolarization in end‐stage renal disease patients. Study group was consisted of 120 dialyzed patients divided into two subgroups: 57 (age 50.7 ± 7.1) were on continuous ambulatory peritoneal dialysis (CAPD) and 73 (age 51.6 ± 7.6) were hemodialyzed (HD). All patients were undergoing three‐dimensional vectorcardiographic (VCG) monitoring to assess parameters concerning T vector: QRS‐T angle, Tel, and Taz. Standard echocardiography was performed to assess: LA_max, LA_short, LA_long. LAVI was calculated due to formula: LAVI = (π/6X [LA_max × LA_short × LA_long])/m². LAVI in HD as well as in CAPD patients was significantly higher compared with controls (respectively: 36.29 ± 10.92; 36.41 ± 11.06; 20.64 ± 6.77 mL/m²). The calculated cutoff value of LAVI was 36.32 mL/m². In HD patients, the strong correlations between LAVI and QRS‐T angle and Tel were determined (respectively: r = 0.407, P < 0.001 and r = 0.359, P = 0.006). Similarly in CAPD group were significant associations between LAVI and QRS‐T angle and Tel (respectively: r = 0.423, P < 0.001 and r = 0.374, P = 0.004). The QRS‐T angle, Tel and Taz are independently and markedly associated with LAVI in both HD and CAPD patients. LAVI and VCG indices are higher in both HD and CAPD patients. Correlation between QRS‐T angle and LAVI may reflect unfavorable influence on the electrical activity of the heart in dialyzed patients with left ventricle diastolic dysfunction. LAVI cutoff value is useful biomarker for stratification of ventricle repolarization disturbances in those patients.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

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.     

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.