The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay

Hemodialysis patients have a higher risk for oxidative stress‐related complications, such as cardiovascular disease and cancer. The increased level of oxidative stress is due to several factors, e.g., the hemodialysis treatment itself and the uremic state. In the present study, the effects of dialysis treatment on the level of DNA breaks and oxidative DNA lesions in mononuclear cells were measured with the comet assay. Factors possibly affecting DNA damage (reported as % DNA in tail) such as the duration of dialysis, time since last dialysis session, years of dialysis treatment, nutritional status (measured as protein catabolic rate), age, and diabetes were also investigated. The levels of DNA breaks (13.6 ± 4.7 before dialysis) and oxidative DNA lesions (7.9 ± 4.8 before dialysis) were significantly higher in dialysis patients (n = 31) compared to the levels of DNA breaks (5.8 ± 1.1) and oxidative DNA lesions (3.4 ± 1.7) in 10 healthy controls (P < 0.001). A decrease of DNA breaks was observed after dialysis (P = 0.038), and the level of oxidative DNA lesions was higher when the time between two treatment sessions were 68 hours compared to 44 hours (P < 0.001). Older subjects had a higher level of DNA breaks (P = 0.003), a good nutritional status predicted a lower level of DNA breaks (P < 0.001), and the duration of the dialysis session was inversely correlated with oxidative DNA lesions (P = 0.014). Diabetes or years of dialysis treatment did not affect DNA damage. The observations in the present study suggest that accumulation of uremic toxins induce DNA damage. The hemodialysis treatment seems to change the DNA damage.     

Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in End‐Stage Renal Disease Patients

In addition to disorders in lipoprotein metabolism, several other factors are involved in the development of atherosclerotic changes in end‐stage renal disease (ESRD) patients. One of these is arterial hypertension. We evaluated serum lipids—total cholesterol (TC), triglycerides (TG), apolipoproteins (A_I , A _II , B, E), lipoprotein(a) [Lp(a)]—in 109 ESRD patients on dialysis [46 on hemodialysis (HD); 63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic patients without renal failure (HL group). Dialysis patients were divided in two groups. Group A included 42 hypertensive patients (mean age: 62.3 ± 15.5 years) whose blood pressure (BP) was satisfactorily controlled with anti‐hypertensive medications. Group B included 67 non hypertensive patients (mean age: 66.6 ± 11.9 years). Levels of Lp(a) were significantly higher in both the HD (p = 0.001) and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a) levels were significantly higher in the hypertensive patients; this difference was not observed among non renal failure patients. These results indicate that arterial hypertension is associated with elevated Lp(a) serum levels in ESRD patients undergoing either HD or CAPD.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Inappropriately elevated endothelin‐1 plays a role in the pathogenesis of intradialytic hypertension

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty‐four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age‐matched and sex‐matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N‐terminal fragment brain natriuretic peptide, renin, angiotensin‐II, aldosterone (ALD), angiotensin‐converting enzyme (ACE), endothelin‐1 (ET‐1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post‐dialysis serum ET‐1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post‐dialysis ratio of NO to ET‐1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post‐dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre‐dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre‐dialysis and post‐dialysis determinations. Compared with blood angiotensin‐II, ALD, ACE, NOR, adrenomedullin, N‐terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET‐1 plasma concentrations may play a predominant role in the pathogenesis of IDH.     

Effects of end‐stage renal disease and dialysis modalities on blood ammonia level

Introduction: Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10‐fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Methods: Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. Findings: No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre‐ and post‐hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Discussion: Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

Platelet‐to‐lymphocyte ratio better predicts inflammation than neutrophil‐to‐lymphocyte ratio in end‐stage renal disease patients

Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end‐stage renal disease (ESRD) patients. Recently, platelet‐to‐lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross‐sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C‐reactive protein, TNF‐α, IL‐6 levels were measured. PLR, NLR, serum high sensitive C‐reactive protein, IL‐6, and TNF‐α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL‐6, and TNF‐α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL‐6, and TNF‐α in this population. When we compared the association of PLR and NLR with IL‐6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF‐α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.     

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Introduction : Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients. Methods : Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential. Findings : Twenty‐five of twenty‐seven patients completed study. The mean serum uric acid levels in the topiroxostat‐treated arm was significantly lower than it in the allopurinol‐treated arm time‐dependently (P < 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat‐arm (*P = 0.0035), but not in allopurinol‐arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation‐reduction potential, and capacity oxidation‐reduction potential between pre and post treatment of both drugs. Discussion : It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.     

The relationship between neutrophil‐to‐lymphocyte ratio and vascular calcification in end‐stage renal disease patients

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri‐aortic calcification (TAC) in end‐stage renal disease (ESRD) patients. Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross‐sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram‐gated 64‐multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.     

Assessment of subjective and hemodynamic tolerance of different high‐ and low‐flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: A randomized controlled trial

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open‐label, randomized, cross‐over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high‐flux, Gambro, Stockholm, Sweden), B (Helixone high‐flux, Fresenius), C (Xevonta high‐flux, BBraun, Melsungen, Germany), and D (Helixone low‐flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1–10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low‐ compared with the high‐flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low‐flux membrane correlated to higher blood pressure levels compared with the high‐flux ones. The Helixone high‐flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.     

Effect of Vitamin E Dialyzer Membrane on Anemia in Hemodialysis Patients

Red blood cell (RBC) survival in patients on chronic maintenance hemodialysis (HD) has been reported to be shortened due to the oxidative damage of RBC membrane. The use of antioxidants might help in the control of anemia and reduce the erythropoietin (EPO) dose needed. Objective: The objective was to determine the effects of vitamin E‐bonded dialyzer membrane (VEM) on anemia and EPO requirements in chronic HD patients. Patients and methods: We prospectively studied 19 stable patients on HD (8 males, age 58.47, range 31–76 years) who were shifted from other dialyzer membranes to VEM for 6 months. At baseline they were given a mean dose of EPO of 90.6 ± 51 U kg^–1 BW^–1 week^–1. Clinical data, dry body weight corrected pre‐dialysis RBC, hemoglobin, reticulocytes, serum iron and ferritin, complete biochemistry, iPTH, and CRP were studied at 3 and 6 months, while therapy scheme was reevaluated monthly. Results: A significant rise, compared to the baseline, was found in hemoglobin and in RBC at 3 months of treatment (12.44 ± 1.16 g/dL vs. 11.2 ± 1.2 g/dL, p = 0.002; and 4.01 ± 0.53 × 10⁶/μL vs. 3.64 ± 0.5 × 10⁶/μL, p < 0.05) and at the end of follow‐up (12.17 ± 1.33 g/dL vs. 11.2 ± 1.2 g/dL, p < 0.05; and 4.03 ± 0.53 × 10⁶/μL vs. 3.64 ± 0.5 × 106/μL, p < 0.05). No significant change in serum iron and ferritin, reticulocytes, EPO dose used, iPTH, Kt/V, or CRP was found at the end of follow‐up compared to the baseline (68.8 ± 17 mg/dL vs. 67.9 ± 18 mg/dL, p = NS; 421 ± 296 mg/dL vs. 478 ± 359 mg/dL, p = NS; 3.76 ± 0.89 × 10⁴/μL vs. 3.82 ± 0.78 × 10⁴/μL, p = NS; 90.2 ± 53 U kg^–1 BW^–1 week^–1 vs. 90.6 ± 51 U kg^–1 BW^–1 week^–1, p = NS; 157 ± 43 pg/dL vs. 148 ± 56 pg/dL, p = NS; 1.21 ± 0.22 vs. 1.2 ± 0.17, p = NS; 7.15 ± 5.42 mg/L vs. 15.38 ± 29.8 mg/L, p = NS, respectively). Conclusions: Despite the small number of patients and the short time interval of treatment, an antioxidant effect of VEM apparently achieved early a better control of anemia in HD patients.     

Treatment of symptomatic coronary artery disease in patients with end‐stage renal disease on hemodialysis with paclitaxel‐eluting TAXUS stent

Percutaneous coronary intervention (PCI) utilizing drug‐eluting stents is becoming a very common revascularization technique in the dialysis cohort; therefore, we sought to identify the impact of dialysis on outcomes in this group of patients. This is a multicenter registry comparing results of 290 patients (186 with normal kidney function, 104 on dialysis) who underwent PCI with exclusive use of paclitaxel‐eluting TAXUS stent. The primary endpoint was an assessment of major adverse cardiac events (MACE) at 1‐ and 2‐year observation. Mean follow‐up was 23.3 ± 6.1 months. Results at 12 months showed: MACE 11.8% vs. 7.7% (P = not significant [ns]), composite major adverse cardiac and cerebrovascular events (MACCE) 12.4% vs. 11.5% (P = ns), all‐cause death 2.7% vs. 8.6% (P < 0.05), cardiac death 2.7% vs. 1.9% (P = ns), target vessel revascularization (TVR) 9.1% vs. 6.7% (P = ns), acute myocardial infarction (AMI) 3.8% vs. 2.9% (P = ns), cerebrovascular events (CVA) 0.5% vs. 1.0% (P = ns); and results at 24 months showed: MACE 17.7% vs. 18.3% (P = ns), MACCE 21.5% vs. 26.0% (P = ns), all‐cause death 4.3% vs. 14.4% (P < 0.01), cardiac death 3.2% vs. 1.9% (P = ns), TVR 14.0% vs. 16.3% (P = ns), AMI 5.4% vs. 5.8% (P = ns), CVA 3.2% vs. 2.9% (P = ns) for non–end‐stage renal disease (ESRD) and dialysis group, respectively. Prior coronary artery bypass graft (CABG) was found to be single risk factor for MACE, TVR, and MACCE in patients with ESRD, while dialysis and prior CABG were found to be single risk factors for death in the entire population. PCI with TAXUS is a feasible procedure and presents promising results in dialysis‐dependent patients.     

Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac,endothelial function and arterial stiffness in ESRD (CERES) cohort

Introduction: Patients with end‐stage renal disease (ESRD) have reduced endothelial function, but whether macro‐ and microvascular endothelial function correlate with baseline risk factors and cardiovascular outcomes in this population is not well understood. Methods: Among 146 participants of the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study, we evaluated macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation (FMD) and velocity time integral (VTI), respectively. We examined cross‐sectional correlations of baseline characteristics, inflammatory and cardiac markers with FMD and VTI. We followed participants for the composite outcome of cardiovascular hospitalization or all‐cause death over fourteen months. Cox survival analyses were adjusted for demographics, comorbidities, medications, systolic blood pressure, inflammation, high‐sensitivity troponin T (hs‐TnT), and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Findings: Impaired VTI was associated with older age and Black race (P < 0.05), as well as female gender, atherosclerosis, and hemodialysis (as opposed to peritoneal dialysis) (P < 0.2). Myocardial injury, measured as hs‐TnT, inflammatory markers and NT‐proBNP correlated with impaired VTI. In unadjusted analyses, VTI was significantly associated with the composite outcome (HR per SD VTI 0.65 [95%CI 0.45, 0.95]), but FMD was not (HR per SD FMD 0.97 [95%CI 0.69, 1.4]). When VTI was calculated as the ratio of (hyperemic VTI‐baseline VTI)/baseline VTI, its association with the outcome persisted after multivariable adjustment. Discussion: Microvascular function was associated with higher rates of cardiovascular hospitalizations and all‐cause mortality among individuals with ESRD on dialysis. Further research is needed to learn whether novel therapies that target microvascular endothelial function could improve outcomes in this high‐risk population.     

End‐stage renal disease from hemolytic uremic syndrome in the United States, 1995–2010

Management of hemolytic uremic syndrome (HUS) has evolved rapidly, and optimal treatment strategies are controversial. However, it is unknown whether the burden of end‐stage renal disease (ESRD) from HUS has changed, and outcomes on dialysis in the United States are not well described. We retrospectively examined data for patients initiating maintenance renal replacement therapy (RRT) (n = 1,557,117), 1995–2010, to define standardized incidence ratios (SIRs) and outcomes of ESRD from HUS) (n = 2241). Overall ESRD rates from HUS in 2001–2002 were 0.5 cases/million per year and were higher for patients characterized by age 40–64 years (0.6), ≥65 years (0.7), female sex (0.6), and non‐Hispanic African American race (0.7). Standardized incidence ratios remained unchanged (P ≥ 0.05) between 2001–2002 and 2009–2010 in the overall population. Compared with patients with ESRD from other causes, patients with HUS were more likely to be younger, female, white, and non‐Hispanic. Over 5.4 years of follow‐up, HUS patients differed from matched controls with ESRD from other causes by lower rates of death (8.3 per 100 person‐years in cases vs. 10.4 in controls, P < 0.001), listing for renal transplant (7.6 vs. 8.6 per 100 person‐years, P = 0.04), and undergoing transplant (6.9 vs. 9 per 100 person‐years, P < 0.001). The incidence of ESRD from HUS appears not to have risen substantially in the last decade. However, given that HUS subtypes could not be determined in this study, these findings should be interpreted with caution.     

Platelet activation and clotting cascade activation by dialyzers designed for high volume online hemodiafiltration

Introduction: Hemodialysis patients are pro‐thrombotic. Higher volume online postdilutional hemodiafiltration (OL‐HDF), with increasing hematocrit increases the risk of clotting in the extracorporeal circuit (ECC). We wished to determine whether OL‐HDF increased platelet activation and ECC clotting. Methods: Coagulation parameters, platelet, white cell, and endothelial activation markers were measured at the start and end of dialysis sessions in 10 patients and also pre‐ and post‐dialyzer after 15 minutes using two different dialyzers designed for high volume OL‐HDF; cellulose triacetate (TAGP) and polysulphone (PS), and polyvinylpyrrolidone (PVP). Patients were anticoagulated with a heparin bolus. Findings: At the start of OL‐HDF, D dimers, thrombin antithrombin complexes (TATs), and soluble adhesions molecules (sICAM‐1 and sVCAM‐1) were increased. Post‐treatment soluble P selectin (PS/PVP 26.7 ± 7.1 versus 36.6 ± 9.9; TAGP 28.7 ± 7.2 versus 43.5 ± 8.4 ng/ml, P < 0.001), and soluble CD40 ligand (PS/PVP 297 ± 228 versus 552 ± 272, TAGP 245 ± 187 versus 390 ± 205 ng/ml, P < 0.05) increased. Post‐dialyzer concentrations increased versus pre‐dialyzer for tissue factor (PS/PVP 117 ± 12 versus 136 ± 16, TAGP 100 ± 25 versus 128 ± 40 ng/ml, P < 0.05), factor VIIIc (PS/PVP 174 ± 54 versus 237 ± 83, TAGP 163 ± 60 versus 247 ± 102 IU/ml, P < 0.01), sVCAM‐1 (PS/PVP 782 ± 64 versus 918 ± 140, TAGP 722 ± 121 versus 889 ± 168 ng/ml, P < 0.01), and D‐dimers (PS/PVP 292 ± 132 versus 355 ± 167, TAGP 300 ± 129 versus 391 ± 171 ng/ml, P < 0.001). There was no macroscopic thrombus noted in the ECC, and no increase in microparticles, platelet factor‐4, or TATs. Discussion: Despite being pro‐thrombotic, with activation of platelets, and lymphocytes during passage through ECC, no macroscopic clotting, or increased TATs were noted during OL‐HDF, and no major differences between cellulosic and polysulphone dialyzers.     

Improving arteriovenous fistula rate: Effect on hemodialysis quality

Vascular access (VA) is the lifeline for patients with end‐stage renal disease on regular hemodialysis (HD). Tunneled catheters have been associated with increased risk of luminal thrombosis, infection, hospitalization, and high cost. Our aims were to follow the “Fistula First Initiative,” avoid or reduce the rate of catheter insertion, improve the rate of arteriovenous fistula (AVF) use, and study the effect of increased AVF use on quality of dialysis and patient's outcome. A VA program has been established in collaboration with an enthusiastic and professional vascular surgery team to manage 358 patients who have been on regular HD treatment for a period ranging from 1 to 252 months. The mean ± standard deviation age of patients was 52 ± 15 years with 62% male patients. Over a period of 2 years, 408 procedures were performed. These include 293 AVFs and 56 arteriovenous grafts (AVGs). Other procedures include 39 permanent catheter insertions, 8 AVF aneurysmectomy, removal of 6 AVGs, embolectomy of 4 AVGs, excision of 1 AVG lymphocele, and ligation of 1 AVF. This program resulted in significant increase in AVF rate from 35% to 82%; reduction in catheter rate from 62% to 10.9%; infection rate down from 6.6% to 0.6%; VA clotting down from 5.1% to 1.0%; and increase in average blood flow rate from 214 ± 32 to 298 ± 37 mL/min (P < 0.01). These results have been associated with improved average single pool Kt/V from 0.88 ± 0.19 to 1.28 ± 0.2 (P < 0.01); increased hemoglobin from 9.2 ± 1.2 to 10.9 ± 0.9 g/dL (P < 0.01); improved serum albumin from 3.2 ± 0.5 to 3.7 ± 0.4 g/dL (P < 0.05); reduction in administered erythropoietin dose by 19%; and significant drop in hospitalization rate from 6.1% to 3.8%. These results confirm the great benefits of AVF on quality of HD and patient outcome, and clearly affirm that AVF should always be considered first.     

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.     

Restless legs syndrome in patients on hemodialysis: Polysomnography findings

Introduction: Restless legs syndrome (RLS) is a highly prevalent sleep movement disorder usually accompanied by periodic limb movements of sleep (PLMS). The incidence of RLS and PLMS in patients with end‐stage renal disease (ESRD) on dialysis is much higher. Clinically, RLS and PLMS can co‐occur. We hypothesized that patients with ESRD on dialysis would have a distinct presentation of RLS, with a higher prevalence of PLMS. Methods: We examined clinical, demographic, biochemical, and polysomnographic characteristics of RLS in patients on dialysis matched to control subjects with normal renal function based on age, sex, body mass index, and frequency of apneas and hypopneas per hour of sleep, defined by the apnea and hypopnea index (AHI), in a proportion of 3:1. Patients with ESRD were on hemodialysis three times per week. Polysomnography was performed overnight in the sleep laboratory. Findings: Patients on dialysis compared to control subjects had a lower amount of N3 sleep (77.6 ± 39.9 minutes vs. 94.8 ± 33.7 minutes, p = 0.037) and REM sleep (55.6 ± 27.5 minutes vs. 74.1 ± 28.4 minutes, p = 0.006), regardless of the presence of RLS. Among the patients on dialysis, those with RLS had higher PLMS. In the control group, patients with RLS had a lower ferritin level, which was not observed in the dialysis group. There was a significant interaction between PLMS and ESRD (p = 0.001), with a higher prevalence of PLMS in patients with ESRD on dialysis in a model adjusted for AHI, sex, arousals, and age. Factors that were associated with PLMS were RLS (p = 0.003), ESRD (p = 0.0001), and AHI (p = 0.041), with an adjusted R² of 0.321. Conclusion: RLS in patients with ESRD on dialysis is independently associated with PLMS, regardless of the severity of sleep apnea, arousals, and age.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

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.