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.     

Hemodialysis‐induced acute pancreatitis secondary to kinked hemodialysis blood lines

Objective: Blood‐membrane interaction during hemodialysis may contribute to inflammatory process, which accelerates the development of atherosclerosis in maintenance hemodialysis patients (MHD). Vitamin E has been widely used against oxidative stress in MHD. One of the strategies for the utilization of vitamin E in MHD patients is the usage of vitamin E‐coated membrane dialyzer. We investigated the effects of vitamin E‐coated membrane dialyzer on serum C‐reactive protein and interleukin‐6, the biomarker of inflammation, compared to polysulfone membrane dialyzer. Methods: Vitamin E‐coated membrane dialyzer (1.5‐m² surface area) and synthetic polysulfone dialyzer (1.5‐m² surface area) were manipulated in a crossover clinical study for 24 weeks in 10 non‐diabetic MHD patients. Run‐in and wash‐out periods (Cellulose tri‐acetate) were performed for 4 weeks before the treatment. Pre‐ and post‐dialysis blood samples were taken at the begining and the end of each dialyzer period (12 weeks). High‐sensitivity C‐reactive protein (hs‐CRP) and interleukin‐6 (IL‐6) were examined. Results: Mean age of the patients was 54.9 years old. CRP and IL‐6 levels were similarly increased after dialysis in both groups (4.8 ± 0.7 and 37.2 ± 9.4, respectively). The CRP and IL‐6 level in vitamin E‐coated membrane dialyzer treatment were lower than in polysulfone treatment (5.0 ± 1.2, p < 0.008 and 67.2 ± 12.4, p < 0.04, respectively). Serum albumin, hemoglobin level, and white blood cell count were not affected by types of dialyzer membrane. Conclusions: In our study, hemodialysis stimulated the inflammation as the previous study. Vitamin E‐coated membrane dialyzer may diminish the inflammatory process in MHD patients and may also prevent further atherosclerosis.     

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

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

Increased oxidative stress in foam cells obtained from hemodialysis patients

Premature atherosclerosis represents the main cause of mortality among end‐stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor‐α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by‐products were measured in the supernatants of macrophage‐derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by‐products, inducible nitric oxide synthase activity, and tumor necrosis factor‐α between patients and controls. Our results, obtained with human macrophages and macrophage‐derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.     

Pre to post‐dialysis plasma sodium change better predicts clinical outcomes than dialysate to plasma sodium gradient in quotidian hemodialysis

Sodium balance across a hemodialysis treatment influences interdialytic weight gain (IDWG), pre‐dialysis blood pressure, and the occurrence of intradialytic hypotension, which associate with patient morbidity and mortality. In thrice weekly conventional hemodialysis patients, the dialysate sodium minus pre‐dialysis plasma sodium concentration (δDPNa+) and the post‐dialysis minus pre‐dialysis plasma sodium (δPNa+) are surrogates of sodium balance, and are associated with both cardiovascular and all‐cause mortality. However, whether δDPNa+ or δPNa+ better predicts clinical outcomes in quotidian dialysis is unknown. We performed a retrospective analysis of clinical and demographic data from the Southwestern Ontario Regional Home Hemodialysis program, of all patients since 1985. In frequent nocturnal hemodialysis, δPNa+ was superior to δDPNa+ in predicting IDWG (R² = 0.223 vs. 0.020, P = 0.002 vs. 0.76), intradialytic change in systolic (R² = 0.100 vs. 0.002, P = 0.02 vs. 0.16) and diastolic (R² = 0.066 vs. 0.019, P = 0.02 vs. 0.06) blood pressure, and ultrafiltration rate (R² = 0.296 vs. 0.036, P = 0.001 vs. 0.52). In short hours daily hemodialysis, δDPNa+ was better than δPNa+ in predicting intradialytic change in diastolic blood pressure (R² = 0.101 vs. 0.003, P = 0.02 vs. 0.13). However, δPNa+ was better than δDPNa+ in predicting IDWG (R² = 0.105 vs. 0.019, P = 0.04 vs. 0.68) and pre‐dialysis systolic blood pressure (R² = 0.103 vs. 0.007, P = 0.02 vs. 0.82). We also found that the intradialytic blood pressure fall was greater in frequent nocturnal hemodialysis patients than in short hours daily patients, when exposed to a dialysate to plasma sodium gradient. These results provide a basis for design of prospective trials in quotidian dialysis modalities, to determine the effect of sodium balance on cardiovascular outcome.     

Increased leukocyte aggregates are associated with atherosclerosis in patients with hemodialysis

Little data are available on the role of blood rheology in atherosclerosis in hemodialysis (HD) patients. This study sought to assess the relationship between leukocytes conjugated with platelets (leukocyte aggregates [LA]) and atherosclerosis in patients with HD. The present study included 118 patients on HD. As surrogate markers of atherosclerosis, aortic stiffness measured by brachial-ankle pulse wave velocity, and carotid intima-media thickness (IMT) were measured. As an assessment of LA, a method, microchannel array flow analyzer, which makes it possible to directly observe the flow of blood cell elements through the microchannel, was used. We measured a number of LA during 50 μL flow of whole blood through microchannels. In 12 age-matched healthy individuals, a number of LA during 50 μL flow of whole blood was 25.7±5.4, whereas in HD patients it was significantly increased up to 48.2±16.4 (P<0.001). Flow cytometry demonstrated that LA were predominantly monocytes. Leukocyte aggregates were positively associated with plasma levels of fibrinogen (P<0.01), or serum high-sensitive C-reactive protein (P<0.01). Moreover, LA had highly significant associations with brachial-ankle pulse wave velocity (P<0.001) and IMT (P<0.001). In conclusion, we demonstrated hemorheologically that monocyte-platelet conjugates play an important role in aortic stiffness and IMT in HD patients.     

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.     

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.     

Role of bicarbonate dialysis in prevention of serious arrhythmias in high‐risk cardiac patients undergoing regular hemodialysis

Background: Cardiac arrhythmias are considered as one of the most important causes of mortality in patients on hemodialysis. Arrhythmias frequently occur in patients with chronic renal failure on regular hemodialysis with reported incidences varying from 30–48% of patients. These abnormalities can span from supraventricular to severe ventricular arrhythmia. There is an increased frequency of occurrence and clustering of arrhythmias around the dialysis time. Aim of the study: To detect the difference between acetate and bicarbonate dialysis as regard to the type and frequency of arrhythmia in those patients. Study design: This study was done on 20 male patients age 51–73, all have history of heart disease. Patients were divided into 2 equal groups using acetate in group 1 and bicarbonate in group 2. All patients were on regular hemodialysis (4 hours, thrice weekly). Careful history and clinical examination were done. Pre‐dialysis investigations included serum creatinine, blood urea nitrogen, serum sodium, potassium, calcium and phosphorus, serum albumin, hemoglobin, and arterial blood gases. Post‐dialysis serum potassium and arterial blood gases were measured. ECG and forty‐eight hours ambulatory monitor (Holter monitor)(before, during, and after hemodialysis, till the end of the dialysis day and throughout the following day) were performed. Results: Group 1 showed significantly less post‐dialysis supraventricular arrhythmias than in dialysis day (210.9 ± 236 and 62.3 ± 14.4), respectively. Significantly less ventricular arrhythmias in post‐dialysis than in dialysis day (30.7 ± 50.4, and 106.2 ± 128.4), respectively. While in Group 2 there were insignificant differences regarding supraventricular arrhythmias (21.9 ± 28.9 and 16.6 ± 36.3) and ventricular arrhythmias (22.9 + 7.8 and 29.6 + 12.8) in dialysis day than in post‐dialysis day. There was significantly higher frequency of supraventricular and ventricular arrhythmias in the dialysis day in acetate hemodialysis in comparison to bicarbonate hemodialysis. Conclusion: Bicarbonate hemodialysis is less arrhythmogenic in comparison to acetate hemodialysis and has better effect on the blood pH and greater degree of base repletion. Continuous ambulatory ECG recording (Holter) is a useful tool in detecting arrhythmias in dialysis patients.     

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.     

Prevalence of hypothyroidism and thyroid nodule in chronic hemodialysis Iranian patients

Introduction: End stage renal disease (ESRD) reasons several changes in the function of thyroid gland as; lower levels of thyroid hormones, altered hormone metabolism, and increased iodine storage. The aim of this study was to evaluate the prevalence of nodular goiter and hypothyroidism in hemodialysis (HD) patients compared with normal population. Methods: This cross‐sectional study was conducted among HD patients and healthy people as the control group for thyroid function evaluation. Thyroid gland was evaluated by physical examination and ultrasonography. Blood level of FT3, FT4, TSH, TPO Ab, and urinary iodine excretion were checked in both groups. Data were analyzed using SPSS‐17 and P‐value less than 0.05 was considered as the significance level. Findings: Eighty six HD patients (57.2 ± 17.2 mean age, 48 men) and 86 healthy people (56.6 ± 16.8 mean age, 48 men) were enrolled in this study. Goiter was confirmed by physical examination in 29.0% of the HD patients and 12.8% of the control group (P = 0.04). Nodular goiter that was shown by ultrasonography was found in 27.9% and 3.5% of the HD and control groups, respectively (P = 0.01). HD patients had a higher frequency of reduced FT3 (40.9% vs. 4.6%, P < 0.01) and increased TSH (18.6% vs. 8.1%, P < 0.03(. TPO Ab was positive in 15.1% of the HD and 11.6% of the control groups (P = 0.14). Discussion: The high incidence of nodular goiter and hypothyroidism in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests, should be considered in evaluations of ESRD patients.     

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.     

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.     

Important role of blood rheology in atherosclerosis of patients with hemodialysis

Concerning a role of blood rheology for atherosclerosis in patients with hemodialysis (HD), little data are available. It may be due to the fact that the method for evaluating rheologic properties of circulating blood has been limited. We examined blood rheology in 118 HD patients by using microchannel array flow analyzer that makes it possible to directly observe the flow of blood cell elements through the microchannel. Transit time (T(B)) of heparinized whole blood through slit pores (7 x 30 microm) was used as an index of rheology and related with various inflammatory biomarkers such as high-sensitive CRP (hsCRP), monocyte chemotactic protein-1, osteopontin, or fibrinogen (Fg). Moreover, as a surrogate marker of atherosclerosis, carotid intima-media thickness (IMT) and aortic stiffness evaluated by brachial-ankle pulse-wave velocity (baPWV) were studied. In HD patients, T(B) had strong positive correlations with hsCRP (r = 0.427; p < 0.00001), Fg (r = 0.452; p < 0.00001), and osteopontin (r = 0.227; p < 0.0134). Further, T(B) was significantly well correlated with IMT (r = 0.400; p < 0.0001) and PWV (r = 0.470; p < 0.0001). Multivariate regression analysis showed that baPWV, IMT, Fg, hematocrit, white blood cell count, and CRP were chosen as significant explanatory factors for T(B.) These results suggest that blood rheology may play an important role for atherosclerosis in patients with HD.     

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.     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

Predictors of cardiovascular events in hemodialysis patients after stress myocardial perfusion imaging

Cardiovascular prognosis in patients under normal stress myocardial perfusion images (MPI) is generally excellent. However, this is not true for patients with chronic kidney disease (CKD) treated by hemodialysis. This study evaluated prognostic factors of adverse cardiovascular events in hemodialysis patients in whom stress MPI was performed. Pharmacological stress MPI was performed in 88 hemodialysis patients, and we retrospectively followed‐up for 26 months. Cardiovascular events included cardiac death, nonfatal myocardial infarction, and unstable angina. Cardiovascular events occurred in 16 patients (18%). Univariate Cox regression analysis revealed that peripheral artery disease (PAD) and parameters of stress MPI were significant predictors of cardiovascular events. Multivariate Cox regression analysis revealed that only PAD (hazard ratio = 6.54; P = 0.002), and abnormal stress MPI (hazard ratio = 8.26; P = 0.008) were independent and significant predictors of cardiovascular events. Kaplan–Meier analysis showed better prognosis in patients with normal stress MPI than in patients with abnormal stress MPI (P < 0.001, log–rank test). However, in patients with normal stress MPI, cardiovascular events occurred in 10 of the 76 patients (13%). Among patients with normal stress MPI, Kaplan–Meier analysis showed that patients with no PAD had better prognosis than patients with PAD (P = 0.001, log–rank test). In hemodialysis patients, both PAD and stress MPI were powerful cardiovascular predictors. Normal stress MPI alone cannot guarantee good prognosis in terms of cardiovascular events. Consideration of PAD may improve the predictive value of stress MPI in some patients.     

Usefulness of assisted procedures for arteriovenous fistula maturation without compromising access patency

Introduction: To increase the rate of arteriovenous fistula (AVF) use, assisted procedures for immature AVF have been strenuously performed. However, this is controversial in that an AVF matured by these assisted procedures may require more frequent intervention to maintain its patency, and have decreased long‐term patency. Methods: Eighty four AVFs that were matured with assisted maturation procedures and 266 AVFs that matured spontaneously without intervention, created between November 2009 and March 2013 from the hemodialysis (HD) vascular access (VA) cohort, were compared retrospectively and we also investigated the factors that may influence AVF long‐term patency. Median follow‐up was 26.8 months (interquartile range, 6.6–45.0 months). Findings: Access survival did not differ between AVFs matured by assisted procedures and spontaneously mature AVFs (P = 0.29). In multivariate Cox regression analysis of AVF survival, age (HR, 1.029; 95% CI, 1.004–1.056; P = 0.024), maturation without assisted procedures 4–6 weeks after AVF creation (HR, 0.233; 95% CI, 0.107–0.506; P < 0.001), and AVF thrombosis (HR, 26.511; 95% CI, 10.986–63.978; P < 0.001) were significantly associated with AVF survival. Performance of assisted procedures to induce AVF maturation did not influence AVF survival (HR, 0.437; 95% CI, 0.191–1.002; P = 0.05). Discussion: Our results support that idea that assisted maturation procedures can ensure the success of immature AVF without compromising long‐term patency. These procedures can be considered more positively for increasing AVF use for VA placement in HD patients.     

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

Introduction: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self‐reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR). Methods: Eighty‐two newly started hemodialysis patients from the SAFIR cohort filled out the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL‐SF^TM) questionnaire at baseline, 6 and 12 months. The SAFIR study was a randomized, placebo‐controlled, double‐blind intervention study, examining the effects of the angiotensin II receptor blocker irbesartan. HRQOL was a secondary outcome measure. Main inclusion criteria: Dialysis vintage <1 year, left ventricular ejection fraction >30% and urinary output >300 mL/day. GFR was measured with mean creatinine and urea clearance from 24‐hour urine collections at baseline, 6 and 12 months. Findings: Irbesartan treatment did not affect HRQOL. Patients were pooled into one group for further analyses. Decline in GFR correlated significantly with decreasing HRQOL over time. HRQOL was stable over time, with a slight nonsignificant tendency toward improved HRQOL. The largest HRQOL‐differences (positive values equal improved HRQOL) observed during the 12 month study period were (mean[95% confidence interval]): Burden of kidney disease:6.4[?2.2;15.0], Role limitations‐physical:12.7[?2.1;27.5], and Role limitations‐emotional:9.7[?5.2;24.6]. Comorbidity, especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. Discussion: Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.     

Evaluation of partial pressure CO2 change in the dialyzer blood inlet during hemodialysis as a measure of vascular access recirculation

Introduction

Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO₂ in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed. The blood returning from the dialyzer in the venous line has significantly higher pCO₂, so in the presence of recirculation, pCO2 in the arterial blood line may increase (ΔpCO₂) during hemodialysis sessions. The aim of our study was to evaluate ΔpCO₂ as a diagnostic tool for vascular access recirculation in chronic hemodialysis patients.

Methods

We evaluated vascular access recirculation with ΔpCO₂ and compared it with the results of a urea recirculation test, which is the gold standard. ΔpCO₂ was obtained from the difference in pCO₂ in the arterial line at baseline (pCO₂T1) and after 5 min of hemodialysis (pCO₂T2). ∆pCO₂ = pCO₂T2–pCO₂T1.

Findings

In 70 hemodialysis patients (mean age: 70.52 ± 13.97 years; hemodialysis vintage of 41.36 ± 34.54, KT/V 1.4 ± 0.3), ∆pCO₂ was 4 ± 4 mmHg, and urea recirculation was 7% ± 9%. Vascular access recirculation was identified using both methods in 17 of 70 patients, who showed a ∆pCO₂ of 10 ± 5 mmHg and urea recirculation of 20% ± 9%; time in months of hemodialysis was the only difference between vascular access recirculation and non-vascular access recirculation patients (22 ± 19 vs. 46 ± 36, p: 0.05). In the non-vascular access recirculation group, the average ΔpCO₂ was 1.9 ± 2 (p: 0.001), and the urea recirculation % was 2.8 ± 3 (p: 0.001). The ΔpCO₂ correlated with the urea recirculation % (R: 0.728; p < 0.001).

Discussion

ΔpCO₂ in the arterial blood line during hemodialysis is an effective and reliable diagnostic tool for identifying recirculation of the vascular access but not its magnitude. The ΔpCO₂ test application is simple and economical and does not require special equipment.