Myocardial stunning in hemodialysis: What is the overall message?

Heart failure and cardiovascular events are common in chronic renal failure. Hemodialysis (HD) causes significant hemodynamic changes and hypotension. New evidence based on intradialytic echocardiography demonstrates transient cardiac dysfunction or stunning in majority of chronic HD patients. Over time, this group may progress to chronic heart failure and appears to predict higher cardiovascular events and mortality. Although the exact etiology is unclear, alterations in HD technique and cardiac medications may reduce this complication. We review the current understanding of acute cardiac stunning during HD and present a systematic management algorithm to optimizing overall outcomes in this high-risk population.     

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

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

The source of net ultrafiltration during hemodialysis is mostly the extracellular space regardless of hydration status

Fluid shifts are common in patients undergoing chronic hemodialysis (HD) during the intradialytic periods, as several liters of fluid are removed during ultrafiltration (UF). Some patients have experienced frequent intradialytic hypotension (IDH). However, the characteristics of fluid shifts and which fluid space is affected remain controversial. Therefore, we designed this study to evaluate the fluid spaces most affected by UF and to determine whether hydration status influences the fluid shifts during HD. This was a prospective cohort study of 40 patients undergoing HD. We measured the patient's fluid spaces using a whole‐body bioimpedance apparatus to evaluate the changes in the fluid spaces before HD and 1–4 hours of HD and 30 minutes after HD. UF achieved during HD by the 40 patients (age, 60.0 ± 5.2 years; 50% men; 50% of patients with diabetes; body weight, 61.3 ± 10.5 kg) was 2.18 ± 0.78 L (measured fluid overload, 2.15 ± 1.24 L). 1) Mean relative reduction of total body water and extracellular water was reduced from the start to the end of HD. 2) However, mean relative reduction of intracellular water was not reduced from the start to the end of HD. 3) No significant differences in fluid shifts were observed according to hydration status. The source of net UF during HD is mostly the extracellular space regardless of hydration status. Thus, IDH may be related to differences in the interstitial fluid shift to the vascular space.     

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.     

Categorization of the hemodynamic response to hemodialysis: The importance of baroreflex sensitivity

Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. The baroreflex arc is under autonomic control and regulates blood pressure. This study aimed to investigate the contribution of impaired baroreflex sensitivity (BRS) to the pathophysiology of IDH. Thirty-four chronic HD (12 IDH-prone, 22 IDH-resistant) patients underwent BRS measurement during HD with relative blood volume monitoring. During analysis, patients were separated into four age-matched groups according to resting BRS≥4.5 ms/mmHg and hemodynamic stability. Resting BRS was extremely heterogenous (geometric mean BRS 5.78±1.41 [range 1.76–41.41] ms/mmHg). Relative blood volume reduction was well matched in all groups (mean reduction in relative blood volume for all patients −6.74%±0.86%, P>0.05). Thirty-seven episodes of IDH occurred in the IDH prone, reduced BRS group. Patients with impaired resting BRS and prone to IDH had markedly different responses to HD as compared to the preserved BRS group, but the total peripheral resistance response was significantly lower than in the IDH-resistant patients (15.9%±2.1% vs. 42.4%±3.0%, respectively, P<0.001). In those patients prone to IDH and with impaired resting BRS, percentage reduction in cardiac output at the end of HD highly correlated with reduction in relative blood volume (r=0.94, P=0.006). Hypotension during dialysis may be an important source of recurrent cardiac injury and early recognition of those patients prone to relative symptomatic and asymptomatic hypotension remains important. Impaired resting BRS and recognition of a suboptimal peripheral pressor response, appear to predict those patients most likely to undergo hemodynamic instability and may assist in the pursuit of this elusive goal.     

Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study

Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case‐control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C‐reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis.     

Effects of citrate‐enriched bicarbonate based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients

Systemic anticoagulation with unfractionated heparin is commonly used in maintenance hemodialysis (HD), but it increases the risk of bleeding complications. We investigated whether the use of citrate‐enriched bicarbonate based dialysate (CD) would reduce systemic anticoagulation without compromising the efficacy of reprocessed dialyzers. This is a crossover study in which half of a total of 30 patients initially underwent HD with acetate‐enriched bicarbonate based dialysate and a standard heparin dose of ～100 IU/kg (Treatment A), whereas the remaining patients were treated with CD and a 30% reduced heparin dose (Treatment B). After 12 consecutive HD sessions in each treatment, the dialysate and heparin doses were reversed, then followed for another period of 12 HD sessions. The two treatment phases were split by a washout period of six HD sessions using acetate‐enriched bicarbonate based dialysate and standard heparin dose. Systemic anticoagulation was higher in Treatment A. The activated partial thromboplastin time at the end of HD session was 68 ± 36 seconds in Treatment A and 47 ± 16 seconds in Treatment B (P = 0.005). Sixty‐eight percent of the dialyzers remained adequate until the 12th use in Treatment A and 61% did so in Treatment B (P = 0.63). Patients had three and 24 cramps episodes during Treatment A and B, respectively (P < 0.001). Nine and 26 symptomatic intradialytic hypotension episodes were seen in Treatment A and B, respectively, (P = 0.003). In conclusion, the use of CD had a favorable effect on anticoagulation in the extracorporeal circuit in patients on maintenance HD, but it was also associated with more hypotension and cramps.     

Does hemodiafiltration reduce vascular stiffness measured by aortic pulse wave velocity compared with high‐flux hemodialysis?

Hemodialfiltration (HDF) has been reported to reduce the frequency of intradialytic hypotension compared with hemodialysis (HD). We wished to determine whether HDF resulted in improvement of arterial stiffness compared with HD. We reviewed peripheral blood pressure and pulse wave velocity measurements in a cross‐sectional analysis of stable HDF and HD outpatients. One hundred forty‐one HDF patients were matched to 148 HD patients in terms of age, sex, prevalence of diabetes, peripheral blood pressure, and body mass. Pulse wave velocity was not different between the HD and HDF cohorts (median 9.1 [8.0–10.7] m/s vs. 9.7 [8.5–11.6] m/s). Similarly, there were no differences in central aortic pressure (149.2 ± 30.9 mmHg vs. 151.9 ± 35.2 mmHg), or aortic (39 [25.1–51.2]% vs. 38.6 [25.8–51.4]%) and brachial (3.8 [?24.3 to 26.9]% vs. 3 [?22.4 to 27.1]%) augmentation indices, respectively. Pulse wave velocity did not differ between adult patients treated by HD and HDF, and similarly, there were no differences in central aortic pressure, aortic or brachial augmentation indices, and cardiac diastolic perfusion. Our study suggests that HDF does not appear to offer any benefit over HD in terms of vascular stiffness.     

Risk factors associated with elevated serum pancreatic amylase levels during hemodialysis

Elevated levels of serum pancreatic enzymes are frequently observed in hemodialysis (HD) patients. The complex hemodynamic, biochemical, and physiological alterations in uremia were speculated to cause excessive release of pancreatic enzymes beyond decreased renal clearance. However, hemodynamic factors are seldom explored in this aspect. We performed the study to evaluate the association between intradialytic hemodynamic change and elevated serum pancreatic amylase (SPA). Eighty‐three prevalent HD patients without any clinical evidence of acute pancreatitis underwent pre‐HD and post‐HD blood sampling for serum pancreatic enzyme levels. Demographic, biochemical, and hematological data were collected from patient record review. Hemodialysis information including intradialytic blood pressure changes and ultrafiltration (UF) amount were collected and averaged for 1 month before the blood sampling day. Patients with elevated SPA during the HD session had greater mean systolic blood pressure and mean arterial pressure reduction, greater UF volume, greater pre‐HD blood urea nitrogen and serum creatinine, higher serum phosphorus, lower pre‐HD serum total CO₂, and lower left ventricle ejection fraction (LVEF). Using multivariate linear and logistic regression analysis, the independent predictors of elevated SPA were determined to be mean arterial pressure reduction during HD, mean UF amount, pre‐HD serum total CO₂, and LVEF. Greater blood pressure reduction during HD, greater UF volume, lower pre‐HD serum total CO₂, and lower LVEF were significantly associated with elevated SPA during HD. This suggests that hemodynamic factors contribute to elevated serum pancreatic enzymes in HD patients.     

Central venous oxygen saturation and thoracic admittance during dialysis: new approaches to hemodynamic monitoring

Intradialytic hypotension (IDH) is one of the most important short-term complications to hemodialysis (HD). Inadequate cardiac filling due to a reduction in the central blood volume is believed to be a major etiological factor. The aim of this study was to evaluate whether these pathophysiologic events are reflected in the central venous oxygen saturation (ScO(2)) and thoracic admittance (TA) during dialysis. Twenty ambulatory HD patients, 11 hypotension prone (HP) and 9 hypotension resistant, with central vascular access, were monitored during 3 HD sessions each. ScO(2), TA, finger blood pressure (BP), and relative change in blood volume (DeltaBV) were measured and sampled continuously. The relative TA decrease and DeltaBV were both largest in the HP group (p<0.05 for both), whereas ScO(2) decreased only in HP patients (p<0.001). Baseline TA was lower in the HP group (p<0.01). Changes in ScO(2) and TA correlated much closer than did changes in ScO(2) and DeltaBV (r=0.43 and 0.18, respectively). Our results suggest that an intradialytic decrease in cardiac output, as reflected by a fall in ScO(2), is a common feature to HD patients prone to IDH. In patients using a central vascular access, ScO(2) and TA measurements may be more specific to the pathophysiologic events preceding IDH than DeltaBV-the current standard monitoring method.     

Patient‐specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one‐compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2‐hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K_M). In this report we determined K_M in patients treated by in‐center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8‐hour HD treatments where intradialytic and postdialytic plasma samples were collected; K_M values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K_M was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K_M values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K_M was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = ?0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one‐compartment model.     

Changes in circulating biomarkers during a single hemodialysis session

The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular‐sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration‐induced hemoconcentration. Among vascular calcification‐related biomarkers, osteoprotegerin and fetuin‐A remained unchanged while fibroblast growth factor‐23 (FGF23) decreased by ?19%. Changes of FGF23 and changes of phosphate correlated (ρ = 0.61, P < 0.001). While C‐reactive protein did not change, interleukin‐6 (IL‐6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL‐6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC‐related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF‐23 and phosphate during HD warrants further studies.     

Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials

Hypertension is a common complication of chronic kidney disease and persists among most patients with end‐stage renal disease despite the provision of conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent HD on blood pressure in the randomized controlled Frequent Hemodialysis Network trials. The daily trial randomized 245 patients to 12 months of 6× (“frequent”) vs. 3× (“conventional”) weekly in‐center hemodialysis; the nocturnal trial randomized 87 patients to 12 months of 6× weekly nocturnal HD vs. 3× weekly predominantly home‐based hemodialysis. In the daily trial, compared with 3× weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by ?7.7 mmHg [95% confidence interval (CI): ?11.9 to ?3.5] and diastolic blood pressure by ?3.9 mmHg [95% CI: ?6.5 to ?1.3]. In the nocturnal trial, compared with 3× weekly HD, 2 months of frequent HD lowered systolic blood pressure by ?7.3 mmHg [95% CI: ?14.2 to ?0.3] and diastolic blood pressure by ?4.2 mmHg [95% CI: ?8.3 to ?0.1]. In both trials, blood pressure treatment effects were sustained until month 12. Frequent HD resulted in significantly fewer antihypertensive medications (daily: ?0.36 medications [95% CI: ?0.65 to ?0.08]; nocturnal: ?0.44 mediations [95% CI: ?0.89 to ?0.03]). In the daily trial, the relative risk per dialysis session for intradialytic hypotension was lower with 6×/week HD but given the higher number of sessions per week, there was a higher relative risk for intradialytic hypotensive requiring saline administration. In summary, frequent HD reduces blood pressure and the number of prescribed antihypertensive medications.     

Comparison of intradialytic blood pressure variability between conventional thrice‐weekly hemodialysis and short daily hemodialysis

Intradialytic blood pressure (BP) variability may be associated with increased mortality. We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice‐weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed‐effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and hypotension (BP<90/55 mmHg at any time during HD). In addition to a predictor and outcomes, the demographics, estimated dry weight, and ultrafiltration ratio were examined. The median (range) age of the patients was 48 (34–77); all had hypertension, and 4 (33%) had diabetes. By a mixed effects linear regression model, the intradialytic systolic BP variability was 13.2 (quartile range 9.5–14.0) mmHg and 10.0 (8.3–10.9) mmHg for CHD and SDHD, respectively (P<0.006). Intradialytic diastolic BP variability was also significantly reduced (7.7 [6.4–9.2] vs. 6.1 [5.5–6.6] mmHg, P=0.005). Relative to CHD, less hypotension was observed during treatment on SDHD: the odds ratio (95% confidence interval) was 0.36 (0.16–0.81; P=0.008). In this retrospective study, SDHD was associated with less intradialytic BP variability and with fewer episodes of hypotension during treatments. Further studies are necessary to generalize these findings.     

Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patients

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

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.     

Dialysate bicarbonate variation in maintenance hemodiafiltration patients: Impact on serum bicarbonate,intradialytic hypotension and interdialytic weight gain

Introduction: The dialysate bicarbonate (DB) influences the acid‐base balance in dialysis patients. Very low and high serum bicarbonate (SB) have been related with a higher mortality. Acid‐base balance also has been associated with hemodynamic effects in these patients. The trial aim was to compare the effect of DB concentration variation on SB levels in maintenance hemodiafiltration (HDF) patients and the effect on intradialytic hypotension and interdialytic weight gain. Methods: A prospective study, with 9 months of follow‐up, involving 93 patients, divided in two groups: group 1 and group 2 with a DB of 34 mmol/L and 30 mmol/L, respectively, with monitoring of pre and post HDF SB, intradialytic hypotension, and interdialytic weight gain. Findings: Pre dialysis SB was higher in group 1: median concentration of 22.7 mmol/L vs. 21.1 mmol/L (P < 0.001). Post dialysis SB levels were higher in group 1: median concentration of 28.0 mmol/L vs. 25.3 mmol/L (P < 0.001). Post dialysis SB in alkalotic range was only detected in group 1 (51.2% of the patients). No significant differences were detected in intradialytic hypotension rate [28.0 vs. 27.4 episodes per 1000 sessions in group 1 and 2, respectively, (P = 0.906)] or in average interdialytic weight gain [2.9% vs. 3.0% in group 1 and 2, respectively, (P = 0.710)]. Discussion: DB of 30 mmol/L appears to be associated with SB levels closer to physiological levels than 34 mmol/L. The bicarbonate dialysate, in the tested concentrations, did not appear to have a significant impact on intradialytic hypotension and interdialytic weight gain in maintenance HDF patients.     

Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3‐dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3‐dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima‐medial thickness, brachial‐ankle pulse wave velocity, ankle‐brachial pressure index, and the cardio‐ankle vascular index. Log‐transformed Kyn/Trp ratio was significantly correlated with log‐transformed time on HD (ρ=0.28, P<0.01), log‐transformed highly sensitive C‐reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=?0.13, P<0.05). A significant association was found between log‐transformed Kyn/Trp ratio and mean carotid artery intima‐medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima‐medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle‐brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.