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.     

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.     

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.     

Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration

Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF) increases middle molecule clearances and has been suggested to increase IS and PCS clearance. We therefore wished to establish whether higher convective clearances with HDF would reduce IS and PCS concentrations. Methods We measured total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On‐line HDF (Ol‐HDF), by high pressure liquid chromatography. Findings Mean patient age was 64.6 ± 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9 months (12.4–62.0). The mean ICS concentration was 79.8 ± 56.4 umol/L and PCS 140.3 ± 101.8 umol/L. On multivariate analysis, IS was associated with serum albumin (β 4.31,P < 0.001), and negatively with residual renal function (β‐4.1,P = 0.02) and vegetarian diet(β‐28.3, P = 0.048) and PCS negatively with log C reactive protein (β‐75.8, P < 0.001) and vegetarian diet (β‐109, P = 0.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2–71.9) vs. 78.1 (49.5–107.5) and PCS (41.6 (14.2–178.3) vs. 127.3 (77.4–205.6) µmol/L, respectively, P < 0.05. Vegetarian patients had lower preOl‐HDF serum urea, and phosphate (13.8 ±3.8 vs. 18.4 ± 5.2 mmol/L, and 1.33 ± 0.21 vs. 1.58 ± 0.45 mmol/L), and estimated urea nitrogen intake (1.25 ± 0.28 vs. 1.62 ± 0.5 g/kg/day), respectively, all P < 0.05. Discussion Plasma IS and PCS concentrations were not lower with Ol‐HDF compared to previous studies in haemodialysis patients. However those eating a vegetarian diet had reduced IS and PCS concentrations. Although this could be due to differences in dietary protein intake, a vegetarian diet may also potentially reduce IS and PCS production by the intestinal microbiome.     

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis

The risk of bleeding is a well‐known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low–molecular‐weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti‐Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.     

Hypoproteinemia as a prognostic risk factor for arteriovenous fistula failure

Introduction: Any vascular access is of limited duration with many factors which influence survival in patients on chronic hemodialysis (HD). Hypoproteinemia as a marker of chronic illness is common among chronic HD patients. Our aim was to analyze the survival of the primary arteriovenous fistula (AVFs) and the risk factors which influence their patency and to test the hypothesis that patients with normal values of serum proteins have lower risk of AVF failure compared to patients with hypoproteinemia. Methods: Seven hundred thirty‐four consecutive patients were included who underwent creation of an AVF. The patients were prospectively followed‐up for 2 years. Only patients with AVF function after a month from its creation were analyzed. The patients were divided into two subgroups, with normal and low serum protein levels (<65 g/L). Findings: At follow‐up 497 (67.7%) AVFs were still functional while 237 (32.3%) AVFs failed due to thrombosis or stenosis. Serum proteins and AVFs created on the forearm were positive predictors while diabetes was a negative predictor of longer AVF survival (P < 0.001; P = 0.003; P = 0.043). When comparing patients with normal and low serum protein levels (<65 g/L), mean survival time was significantly longer in patients with normal serum levels (P < 0.001). Discussion: In this study, hypoproteinemia was an independent prognostic marker for AVF failure at 2 years. Hypoproteinemia, based on our results, is an independent, more sensitive and prognostic marker of possible vascular access failure than the presence of other common factors which influence shorter AVF survival.     

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.     

Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis—sevelamer hydrochloride,calcium carbonate,and bixalomer

The serum bicarbonate (HCO₃^–) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end‐stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO₃^– levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO₃^– level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO₃^– levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P < 0.05). Metabolic acidosis was not observed in four patients (serum HCO₃^– level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer.     

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.     

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.     

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.     

Does the presence of an arteriovenous fistula alter changes in body water following hemodialysis as determined by multifrequency bioelectrical impedance assessment?

Multifrequency bioelectrical impedance assessments (MFBIAs) aid clinical assessment of hydration status for hemodialysis (HD) patients. Many MFBIA devices are restricted to whole body measurements and as many patients dialyze using arteriovenous fistulas (AVFs), we wished to determine whether AVFs affected body water measurements. We reviewed pre‐ and post‐HD segmental MFBIA measurements in 229 patients attending for midweek HD sessions. Up to 144 were dialyzed with a left arm AVF (L‐AVF), 42 with a right arm AVF (R‐AVF), and 43 by central venous access catheter (CVC). Water content and lean tissue were greater in the left compared to right arm in those patients with L‐AVFs both pre and post dialysis (pre 2.1 ± 0.7 vs. 2.0 ± 0.7 L, and post 1.9 ± 0.6 vs. 1.8 ± 0.6 L and pre 2.65 ± 0.9 vs. 2.56 ± 0.8 kg, and post 2.34 ± 0.8 vs. 2.48 ± 0.8 vs. 2.34 ± 0.8 kg, respectively) and were also greater in the right compared to left arm for those patients dialyzing with R‐AVFs (pre‐HD 1.92 ± 0.5 vs. 1.86 ± 0.6 L and post‐HD 1.79 ± 0.5 vs. 1.7 ± 0.5 L, and pre‐HD 2.47 ± 0.6 vs. 2.38 ± 0.7 kg and post‐HD 2.3 ± 0.74 vs. 1.28 ± 0.7 kg, respectively), all Ps < 0.05. There were no significant differences in arm volumes or composition pre or post dialysis in those dialyzing with CVCs. Segmental MFBIA detects differences in arm water and lean mass in patients with AVFs. The presence on an AVF increases the water content in the ipsilateral arm both pre and post HD. This increased water content of the fistula arm will not be detected by whole body bioimpedance devices.     

Effect of Valsalva Maneuver on QT Dispersion in Hemodialysis Patients

Increased QT dispersion seems to be related to an increased risk of arrhythmia and sudden death, a common cause of mortality in hemodialysis (HD) patients. Increase in sympathetic tone has been documented in HD patients. In this study, we aimed to investigate the effect of changes in the autonomic tone on QT dispersion (QTd) in HD patients. Twenty HD patients (M/F 13/7; age, mean ±SD, 28 ± 10 years) and 22 age‐ and sex‐matched healthy controls (M/F 12/10; age, 30 ± 10 years) were included. The patients were dialyzed three‐times weekly; time on dialysis was 17 ± 8 months. The QT durations were measured from 12 lead surface EKGs and were corrected for RR intervals. Corrected maximum (QT_c max) and minimum (QT_cmin) QT intervals and their difference (QT _c d) were recorded. The effect of the Valsalva maneuver in the release phase on QT _c intervals and dispersion was assessed. The HD patients had prolonged values compared to controls: QT _c d, 59 ± 17 ms versus 35 ± 7 ms, p < 0.001; QT _c max, 458 ± 41 ms versus 397 ± 21 ms, p < 0.001; and QT _c min, 398 ± 36 ms versus 362 ± 25 ms, p < 0.001. After the Valsalva maneuver no changes were observed in controls: QT _c max, 397 ± 21 ms versus 396 ± 22 ms, p = 0.9; QT _c min, 362 ± 24 ms versus 358 ± 19 ms, p = 0.5; and QT _c d, 35 ± 7 ms versus 38 ± 10 ms, p = 0.15. Whereas, in HD patients all values were significantly shortened: QT_cmax, 458 ± 41 ms versus 427 ± 35 ms, p = 0.003; QT_c min, 398 ± 36 ms versus 379 ± 34 ms, p = 0.04; and QT_c d, 59 ± 17 ms versus 48 ± 15 ms, p = 0.01. The decrease in QTmax was more prominent than the decrease in QTmin, hence QT dispersion was significantly decreased after the Valsalva maneuver, but differences from controls were still significant. In conclusion, increased sympathetic activity may have a role in the prolonged QT duration and increased QT dispersion in HD patients.     

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.     

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.     

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.     

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.     

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.     

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.