Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular–weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.     

Middle molecules removal. Beyond beta2-microglobulin

The uremic toxin removal capacity mainly depends on dialyzer and hemodialysis modes. The low-flux hemodialysis only removes solutes having molecular weights less than 5.000 Da. High-flux hemodyalisis represents a form of low-volume hemodiafiltration because of the internal filtration and back-filtration that can take place within a dialyzer. Hemodiafiltration with large volumes of replacement fluid seems to be the best technique for removing all small, medium-sized and large molecules. The objective of our study was to evaluate the large molecules removal bigger than beta2-microglobuline on high flux haemodialysis and on-line hemodiafiltration with postdilutional infusion, in patients with three times a week dialysis and on short daily dialysis. We studied 24 patients, 15 males and 9 females stable on haemodialysis programme, twelve on standard four to five hours three times a week dialysis and twelve on 2 to 2 1/2 hours six times a week dialysis. All patients were dialysed with Fresenius 4008 monitor, three sessions on high flux haemodialysis (HD) and three sessions on on-line hemodiafiltration (OL-HDF). Two sessions with each filter were performed (polisulfone HF80, polyethersulfone Arylane H9 and new polisulfone APS 900). Pre and postdialysis concentrations of urea, creatinine, (beta2-microglobulin (beta2-m), myoglobin, prolactin and alpha1 microglobulin (alpha1-m) were measured. There was no difference in urea and creatinine small molecules removal. beta2m removal was 68% on HD and 81% on OL-HDF. Myoglobin and prolactin present a similar removal pattern, a higher removal with new filters (60% with Arylane and 59% with APS) in comparison with clasical polisulfone (22% with HF80). The mean alpha1-m reduction rate on HD was 6% and on OL-HDF 22%. OL-HDF with APS 900 filter was the most remove technique (35.4%), significatively higher than the other modes and filters. We can conclude that the new filters generation reach a better uremic toxins removal, specially in large molecules higher than beta2-m and on HD modality.     

Is High‐Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end‐stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL‐HDF). The aim of the study was to assess the nutritional status of patients on high‐volume OL‐HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty‐eight patients with ESRD undergoing postdilution OL‐HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross‐sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta‐2‐microglobulin (84.2 ± 3.8%) and cystatin‐C (81.6 ± 3.47%). Beta‐2‐microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin‐C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL‐HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.     

Acute Intradialytic Cardiac Function and Inflammatory Cytokine Changes During High‐Efficiency Online Hemodiafiltration With Acetate‐Free and Standard Dialysis Solutions

Acetate in standard acetate‐containing bicarbonate (AC) dialysis fluid could induce peripheral vasodilatation, suppression of myocardial function, and inflammatory cytokine production, resulting in intradialytic hypotension in conventional hemodialysis (HD) patients. Online hemodiafiltration (HDF) provides superior hemodynamic stability over HD. The potentially additive hemodynamic benefits of the novel acetate‐free bicarbonate (AF) dialysis fluid in online HDF have never been explored before. The present randomized, double‐blind, crossover study was conducted in 22 online HDF patients to investigate the impact of AF dialysis fluid on hemodynamic and cytokine changes compared with AC dialysis fluid in online HDF. The results demonstrated the comparable changes of arterial pressure between AF and AC online HDF. During the study periods, the incidences of composite intradialytic hypotension and other adverse events were not different. The baseline and hourly changes of cardiac index, cardiac output, and peripheral vascular resistance during dialysis were comparable (P = 0.534, 0.199, and 0.641, respectively). The percent reductions of NT‐proBNP and cTnT were not significantly different (72.6 ± 12.3 vs. 72.6 ± 12.8%, P = 0.99 and 35.2 ± 12.8 vs. 36.7 ± 12.0%, P = 0.51). The changes of all pro‐inflammatory cytokines (IL‐2β, IL‐6, IL‐8, and TNF‐α) and anti‐inflammatory cytokine (IL‐10) during dialysis were comparable between both groups. In conclusion, AF dialysis solution does not offer additional hemodynamic benefit for stable online HDF patients. The hemodynamic stability provided by online HDF might protect the adverse effects of acetate.     

Pulmonary gas exchange during dialysis in patients with obstructive lung disease

Hypoxemia occurs during routine hemodialysis and may contribute to morbidity, but its cause is not well understood. We reasoned that patients with COPD would be more vulnerable to abnormalities in gas exchange with dialysis. Thus, to investigate the cause of dialysis-related hypoxemia, we measured gas exchange in a group of stable dialysis patients with normal pulmonary function (n = 6) and a group of dialysis patients with COPD (n = 6). Measurements were made predialysis, at 1 h, and postdialysis with both acetate and bicarbonate dialysates. Acetate dialysis decreased PaO2 in normal and COPD patients at 1 h and postdialysis. Acetate-induced hypoxemia was associated with reduced respiratory CO2 excretion and hypoventilation but PaCO2 did not change. This decrease in CO2 excretion resulted from CO2 fixation during acetate metabolism and modest CO2 loss across the dialyzer. Hypoxemia occurred only postdialysis with bicarbonate dialysate in normal and COPD patients. An increased P(A-a)O2 occurred postdialysis with both dialysates, and was most consistently observed in the COPD patients. In summary, at least two mechanisms contribute to dialysis hypoxemia. With acetate dialysate, alveolar hypoventilation from CO2 unloading occurs at 1 h and postdialysis due to acetate metabolism. However, abnormalities in ventilation/perfusion contribute to postdialysis hypoxemia observed with both dialysates. In addition, the decrement in PaO2 associated with dialysis is similar in normal and COPD patients, although preexisting COPD makes postdialysis changes more apparent.     

血液透析滤过对慢性肾功能衰竭患者血清瘦素水平的影响

目的探讨血液透析滤过对慢性肾功能衰竭患者血清瘦素的清除及血清瘦素水平与营养不良的关系。方法测定41例维持性血液透析患者透析前、后(血液透析组22例,血液透析滤过组19例)及35例对照组血清瘦素、尿素氮、肌酐、白蛋白、总胆固醇和血红蛋白水平,计算体重指数(BM I)。结果维持性血液透析患者透析前血清瘦素水平均较对照组明显增高。血液透析滤过组透析后血清瘦素水平较透析前明显降低。维持性血液透析患者的血清瘦素水平分别与BM I呈正相关,与血清白蛋白呈负相关。结论慢性肾功能衰竭患者存在高瘦素血症,血清瘦素水平升高与营养不良有相关性,血液透析滤过可清除血清瘦素。     

Evaluation of Intradialytic Hypertension Using Bioelectrical Impedance Combined With Echocardiography in Maintenance Hemodialysis Patients

Although intra‐dialytic hypertension (IDH) has been noted in clinical settings for many years, its pathogenesis remains unclear. In this cross‐sectional study, we analyzed IDH incidence in our center and the correlation between postdialysis volume state and IDH. One hundred thirty‐one maintenance hemodialysis (MHD) patients were enrolled in our study, and bioelectrical impedance (BIA) and echocardiography (ECG) were recorded. In addition, demographic data were collected, and laboratory examinations were conducted. The patients were grouped into four groups according to the change in systolic blood pressure (SBP) between predialysis and postdialysis. The incidence of IDH was 10.7%. The proportion of extracellular water to total body weight (ECW/TW), as evaluated by BIA, was significantly higher in the IDH group than in the other three groups both in pre‐and post‐dialysis. In particular, postdialysis SBP was highest in the highest tertile interval of ECW/TW. In addition, among the four groups, left ventricular volume (LVV) was highest in the IDH group. Binary logistic analyses revealed that predialysis SBP, postdialysis ECW/TW and LVV were independent risk factors of intradialytic hypertension. When predicting IDH, the AUC of the ROC curve was higher for ECW/TW combined with LVV (0.752, 95% CI 0.613–0.896) than for either LVV or ECW/TW alone. Our study further showed that post‐dialysis volume expansion is an important factor for the development of IDH.     

DNA Methylation: Hemodialysis Versus Hemodiafiltration

Aberrant DNA methylation is an emerging characteristic of chronic kidney disease including dialysis patients. It appears to be associated to inflammation. We compared the global DNA methylation status in 10 control subjects compared to 80 dialysis patients (N = 40 on‐line hemodiafiltration, N = 40 high‐flux hemodialysis) in relation to the dialysis technique and inflammation. Whole blood DNA methylation was assessed with a 5‐mc DNA enzyme linked immunosorbent assay Kit. Global DNA methylation was higher in hemodialysis (HD) compared to on‐line hemodiafiltration (HDF) patients (0.045 vs. 0.039; P < 0.0001) and controls (0.045 vs. 0.0284; P = 0.0002 for HD; 0.039 vs. 0.0284; P = 0.0254 for on‐line HDF). To study the influence of the dialysis technique on DNA methylation we divided dialysis patients according to the median value of 5‐mC. DNA methylation was highest in inflamed patients on hemodialysis. The dialysis technique was the only independent predictor of global DNA methylation in dialysis patients. On‐line HDF could be associated with a favorable DNA methylation profile.     

血液透析患者透析充分性的监测

目的　评价血液透析充分性的临床标准和尿素动力学模型 (UKM )参数 ,并观察透析后尿素反跳 (PDUR)对评价的影响。方法　按临床标准分为透析充分组 (Ⅰ组 )和透析不充分组 (Ⅱ组 ) ,分别计算PDUR以及反跳前后UKM参数即尿素清除指数 (Kt/V)、尿素时间平均浓度(TACurea)、蛋白分解率 (PCR)。结果　两组PDUR、尿量以及反跳前后的UKM参数存在显著性差异(P <0 .0 1) ;G S图显示Ⅱ组临床和参数判断基本一致 ,但Ⅰ组存在较大差异 ;平均PDUR为 17.8% ,反跳后的Kt/V、PCR值较反跳前分别下降 18.7%和 12 .7% ,而TACurea值增加 3 .1% ,PDUR与透析间尿量呈负相关 (r=-0 .64 )。结论　透析充分性评价是一连续非短期过程 ,宜综合临床和参数指标判断 ,以后者为主 ;忽视PDUR将高估透析充分性 ,宜用透析后尿素平衡浓度计算参数 ;透析不充分和残存肾功能可能影响PDUR程度。     

Importance of Body Water in the Efficacy of Convective Solute Transport in Online Hemodiafiltration

High‐volume online hemodiafiltration (OL‐HDF) has been associated with improved patient survival compared to conventional hemodialysis in recent trials, where the importance of convective volume (CV) in this benefit is noted. The purpose of this study was to determine the corporal composition parameters influencing the efficacy of CV in the removal of different molecular weight (MW) molecules. Demographic data, corporal composition parameters with bioimpedance spectroscopy, dialysis features and the reduction rates of different MW molecules in a four‐hour OL‐HDF session were collected in 61 patients. We observed a significant negative correlation of β2‐microglobulin, cystatin‐C, myoglobin and prolactin reduction rates with body surface area, weight, total body extracellular (ECW) and intracellular water (ICW), lean tissue mass and body cellular mass. The multivariable regression analysis identified ECW and ICW as the only corporal composition factors independently associated to the relative elimination of β2‐microglobulin (Beta: –0.801, P = 0.002 for ECW and Beta: –1.710, P = 0.001 for ICW), cystatin‐C (Beta: –0.656, P = 0.010 for ECW and Beta: –1.511, P = 0.004 for ICW) and myoglobin (Beta: –0.745, P = 0.014 for ECW and Beta: –2.103, P = 0.001 for ICW), in addition to CV. Prolactin reduction was only associated with ICW (Beta: –1.540, P = 0.028). When adjusting CV with ECW and ICW, only the ratio CV/ECW was an independent predictor for higher elimination of β2‐microglobulin, cystatin‐C and myoglobin. The corporal composition parameters independently associated to the reduction of medium‐sized molecules are the extracellular and intracellular water. The ratio “convective volume/extracellular water” predicts higher efficacy of convective transport. Adjusting the convective volume to patient features could be useful to monitor the efficacy of OL‐HDF and to prescribe individualized therapies.     

Systolic Blood Pressure and Mortality in Chronic Hemodialysis Patients: Results of a Nationwide Italian Study

Studies on the relationship between blood pressure (BP) and mortality among hemodialysis patients have yielded conflicting results. Reports have come mostly from North America and have dealt with dialysis patients as a homogenous population and differed in methods and time of BP measurement and the optimal BP target. In a prospective nationwide study in 3674 unselected Caucasian patients with end‐stage renal disease undergoing chronic hemodialysis from 73 dialysis units, the authors sought to examine the relationship between the different measurements of BP and mortality according to antihypertensive treatment. The mean age of patients was 67.2±14.1 years and the prevalence of diabetes was 19.5%. During follow‐up (26.5±10.5 months), 977 deaths were recorded. In the whole cohort, BP was not associated with mortality. After grouping the patients according to antihypertensive treatment, the analysis showed that only in patients who did not take antihypertensive medications (1613) was there an inverse relationship between postdialysis systolic BP and mortality. These patients differed from the others in BP, dialysis vintage, prevalence of diabetes, and type of dialysis technique. This study suggests that with respect to the relationship of BP with mortality, dialysis patients are not a homogenous population. Differences in demographic characteristics and in dialysis technique may therefore explain the reported variability of previous results.     

Evaluation of methods to calculate dialysis dose in daily hemodialysis

Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiological. Different methods have been described to calculate dialysis dose which take into consideration change in frequency. The aim of this study was to calculate all dialysis dose possibilities and evaluate the better and practical options. Eight patients, 6 males and 2 females, on standard 4 to 5 hours thrice weekly on-line hemodiafiltration (S-OL-HDF) were switched to daily on-line hemodiafiltration (D-OL-HDF) 2 to 2.5 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Time average concentration (TAC), time average deviation (TAD), normalized protein catabolic rate (nPCR), Kt/V, equilibrated Kt/V (eKt/V), equivalent renal urea clearance (EKR), standard Kt/V (stdKt/V), urea reduction ratio (URR), hemodialysis product and time off dialysis were measured. Daily on-line hemodiafiltration was well accepted and tolerated. Patients maintained the same TAC although TAD decreased from 9.7 +/- 2 in baseline to a 6.2 +/- 2 mg/dl after six months, p < 0.01. No significant changes were observed in weekly Kt/V and eKt/V throughout the study. However EKR, stdKt/V and weekly URR were increased during D-OL-HDF in 24-34%, 46% and 50%, respectively. Hemodialysis product was raised in a 95% and time off dialysis was reduced to half. CONCLUSION: Dialysis frequency is an important urea kinetic parameter which there are to take in consideration. It's necessary to use EKR, stdKt/V or weekly URR to calculate dialysis dose for an adequate comparison between different frequency dialysis schedules.     

Online Hemodiafiltration Reduces Bisphenol A Levels

Several uremic toxins have been identified and related to higher rates of morbidity and mortality in dialysis patients. Bisphenol A (BPA) accumulates in patients with chronic kidney disease. The aim of this study is to demonstrate the usefulness of online hemodiafiltration (OL‐HDF) in reducing BPA levels. Thirty stable hemodialysis patients were selected to participate in this paired study. During three periods of 3 weeks each, patients were switched from high‐flux hemodialysis (HF‐HD) to OL‐HDF, and back to HF‐HD. BPA levels were measured in the last session of each period (pre‐ and post‐dialysis) using ELISA and HPLC. Twenty‐two patients (mean age 73 ± 14 years; 86.4% males) were included. Measurements of BPA levels by HPLC and ELISA assays showed a weak but significant correlation (r = 0.218, P = 0.012). BPA levels decreased in the OL‐HDF period of hemodialysis, in contrast to the HF‐HD period when they remained stable (P = 0.002). In conclusion, OL‐HDF reduced BPA levels in dialysis patients.     

Dialysis dose and the diagnosis of hypertension in hemodialysis patients

OBJECTIVE: To determine whether simultaneous consideration of pre and postdialysis blood pressure (BP) can improve the prediction of interdialytic ambulatory BP in hemodialysis patients, we analyzed BP obtained before and after dialysis using routine or standardized methods and by self-measurement at home in 104 hemodialysis patients. Evidence for effect modification was tested for several plausible demographic, clinical and laboratory factors. RESULTS: Postdialysis BP when considered jointly with predialysis BP improved the diagnostic performance of standardized dialysis unit BP measurements [receiver operating characteristic (ROC) area under the curve (AUC) 0.91 for joint, 0.85 for prehemodialysis ROC (P=0.01 for difference in AUC)]. A trend to improvement existed in ROC AUC with routine dialysis unit BP measurement [ROC AUC 0.88 for joint, 0.82 for prehemodialysis ROC (P=0.055 for difference in AUC)]. Dialysis dose measured by urea reduction ratio was a strong effect modifier for the determination of hypertension by routine (P=0.012) and standardized (P=0.002) dialysis unit BP measurements. This effect modification was not seen with home BP (P=0.26). CONCLUSION: Simultaneous consideration of predialysis and postdialysis BPs obtained over 2 weeks can improve the diagnosis of hypertension in hemodialysis patients. Dialysis dose may significantly influence the diagnosis of hypertension when dialysis unit BPs are used.     

Effect of Hemodialysis on the Red Blood Cell Life Span in Patients with End‐Stage Kidney Disease

The aim of this study was to use a CO breath test to investigate hemodialysis effects on red blood cell lifespan in patients with chronic kidney disease. A cohort of 17 non‐smoking men with end‐stage kidney disease undergoing hemodialysis via a polysulfone dialysis membrane (as opposed to a traditional cellulose acetate membrane) were subjected to a repeated Levitt's CO breath test to compare red blood cell lifespan before vs. after dialysis. None of the patients showed significant fluctuations in endogenous CO concentration during the dialysis procedure. The mean red blood cell lifespan was 66.0 ± 31.0 days before dialysis and 72.0 ± 26.0 days after dialysis, with no significant difference between the assessment time points (P > 0.05). In conclusion, dialysis using a polysulfone membrane did not appear to disrupt red blood cells or reduce their lifespan in patients with end‐stage kidney disease.     

High cut-off membrane hemodiafiltration in myoglobinuric acute renal failure: a case series

Acute renal failure is a major complication of rhabdomyolysis. New membranes for hemodialysis have been developed with a high cut-off pore size allowing efficient removal of myoglobin. We report on six patients treated by hemodiafiltration with a high cut-off membrane (HCO-HDF) for myoglobinuric acute renal failure. Rhabdomyolysis was caused by infection in two patients, by a statin in one patient and a non-traumatic crush in another, and followed cardiovascular surgery in two others. Ten HCO-HDF procedures were performed. A high cut-off hemofilter was used, with citrate anticoagulation and postdilutional fluid substitution of 2-3 L/h, dialysate flow 500 mL/min, and blood flow within 250-300 mL/min. Albumin losses were replaced by infusion of human albumin solution, and the mean myoglobin reduction ratio was 77% (range, 62-89%). An excellent clearance of 81 mL/min (range 42-131 mL/min) was achieved. Nearly 5 g of myoglobin was removed into the dialysate collected in one of the procedures. A high rebound in serum myoglobin, on average to 244% of the post-procedure myoglobin level, was observed. The four patients alive at the time remained anuric for a week. Slow myoglobin elimination with a mean half-time of 39 h (range 19-59 h) was observed in that period. Highly efficient myoglobin removal by high cut-off membrane hemodiafiltration was demonstrated in our patients. Rapid redistribution from the extracellular fluid and sustained myoglobin release were suggested by the high rebound observed. Elimination of myoglobin within the body was shown in our study to occur slowly during the period of anuria.