Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients.

BACKGROUND: Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required. Modifications of the dialysis regimen may result in a better removal of Hcy. We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients. METHODS: Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux, a high-flux and a super-flux membrane, in random order. Pre-dialysis tHcy was determined at baseline and every 4 weeks. In 18 patients, plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured. RESULTS: Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis (-14.6 +/- 2.8%), whereas it remained stable during high-flux (+0.5 +/- 2.4%) and low-flux dialysis (+1.7 +/- 3.2%). The homocysteine reduction ratio was not different for the three membranes: 0.39 +/- 0.03 for the super-flux, 0.47 +/- 0.02 for the high-flux and 0.39 +/- 0.02 for the low-flux dialyser. The amount of Hcy recovered in the dialysate during a single dialysis session was also similar: 117.5 +/- 3.6 micro mol during super-flux, 95.3 +/- 11.5 micro mol during high-flux and 116.5 +/- 11.6 micro mol during low-flux dialysis. CONCLUSION: Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients. Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes, rather than better dialytic clearance of Hcy itself, may explain the beneficial effect of the super-flux membrane.     

Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients.

BACKGROUND: Free immunoglobulin light chains (FLCs) have previously been shown to be uraemic toxins. In this work we investigated the effect of haemodialysis and haemodiafiltration on the level of FLCs in serum/plasma of uraemic patients. METHODS: Serum/plasma proteins were separated by non-reducing SDS-PAGE and transferred to a nitro-cellulose membrane. FLCs were detected by specific antibodies and an enhanced chemiluminescence detection system. The FLC concentrations were calculated. We studied 15 healthy subjects, 10 patients with chronic renal failure, 71 patients undergoing haemodialysis treatment and 33 patients treated with haemodiafiltration. Different membranes were compared: low- and high-flux polysulfone membranes, low- and high-flux cellulose triacetate membranes, high-flux polymethylmethacrylate and polyacrylonitrile membranes. RESULTS: Chronic renal failure patients showed elevated FLC concentrations as compared with controls. In haemodialysis or haemodiafiltration patients these values were even higher. This was mainly due to an increased concentration of FLC of the lambda-type. The treatment modality per se did not influence the FLC concentrations. Only haemodialysis or haemodiafiltration with the polymethylmethacrylate membrane lead to a significant reduction in FLC concentrations; however, these did not reach control levels. We did not observe differences in FLC levels between patients with different underlying diseases, nor did we find a correlation between age or the duration of the dialysis treatment and FLC concentrations. We found a positive correlation between FLC concentrations at the beginning of dialysis treatment and the amount of IgLCs removed during treatment. However, the average FLC level after treatment did not reach control values. CONCLUSIONS: Currently available haemodialysis or haemodiafiltration treatments are unable to normalize the elevated serum/plasma levels of FLCs in end-stage renal disease patients.     

Modalities of Continuous Renal Replacement Therapy: Technical and Clinical Considerations

Continuous renal replacement therapies (CRRT) are continuous forms of renal functional replacement used to manage acute kidney injury (AKI) in the critically ill patient. Depurative mechanisms include convection, diffusion, and membrane adsorption utilizing high-flux highly permeable biocompatible dialysis membranes. The simultaneous infusion of replacement fluid permits fluid removal without intravascular volume contraction and better hemodynamic stability, metabolic control to almost normal parameters, and removal of large-size toxins and cytokines. Moreover, CRRT allows better long-term clearance of small and middle molecules than other dialysis modalities. This article focuses on the different modalities of CRRT and reviews both the basic concepts and the newest approaches to the management of the critically ill patient with AKI.     

High-flux dialyzers, backfiltration, and dialysis fluid quality

Currently, high-flux hemodialysis is the most common mode of dialysis therapy worldwide. Its steadily increasing use is largely based on the desire to reduce the excessively high morbidity and mortality of end-stage renal disease patients maintained on conventional dialysis (low-flux, mostly cellulosic membranes) by offering better biocompatibility and enhanced removal of uremic toxins. Two large randomized trials suggest a survival benefit for selected subgroups of high-flux dialysis patients such as diabetics, patients with hypoalbuminemia, or patients who have been on dialysis for a long period (>3.7 years). The major disadvantage of high-flux hemodialysis relates to the use of dialysis fluid, which is commonly not pure and may endanger patients treated with high-flux hemodialysis. Endotoxin fragments and other bacterial substances derived from bacteriologically contaminated dialysis fluid may, even at bacterial counts or endotoxin concentrations within the limits of accepted standards of dialysis fluid purity, enter from the dialysate into the patient's blood either by convective transfer (backfiltration) or by movement down the concentration gradient (backdiffusion). Repeated exposure of high-flux hemodialysis patients to backtransport of dialysate contaminants aggravates the uremia-associated inflammatory response syndrome and contributes to long-term morbidity. At present, the only solution to circumvent the risks of backtransport is the use of dry powder cartridges for bicarbonate concentrate and the use of bacteria- and endotoxin-retentive filters for the online production of ultrapure dialysis fluid. Use of ultrapure dialysis fluid (bacteria <0.1 CFU/ml and endotoxin <0.03 IU/ml) has been found to reduce inflammation and comorbidities in clinical investigations compared to commercial dialysis fluid. The European Renal Association and a number of national societies in Europe or in Japan strongly recommend the use of ultrapure dialysis for high-flux hemodialysis.     

Potential of dual-skinned, high-flux membranes to reduce backtransport in hemodialysis

BACKGROUND: Potential backfiltration of cytokine-inducing material is a clinical concern during hemodialysis conducted with high-flux membranes. Novel hollow-fiber membranes were developed that had asymmetric convective solute transport properties, aimed at reducing the passage of potentially harmful molecules from dialysate to blood, while maintaining the desired fluid and solute movement from blood to dialysate. METHODS: Sieving coefficient as a function of molecular weight was measured in vitro using polydisperse dextrans. Measurements were conducted using two different flat-sheet membranes in series or using hollow fiber membranes having two integrally formed skin layers. Based on measured experimental parameters, model calculations simulated the performance of a clinical-scale dialyzer containing these new membranes versus that of a commercially available high-flux dialyzer. RESULTS: Asymmetric convective solute transport was demonstrated using both commercial flat-sheet and newly developed hollow-fiber membranes. For two flat-sheet membranes in series, the extent of asymmetric transport was dependent on the order in which the solution was filtered through the membranes. For the hollow-fiber membranes, the nominal molecular weight cut-off was 20 kD in the blood-to-dialysate direction and 13 kD in the dialysate-to-blood direction. For this membrane, model calculations predict that clearance of a beta2-microglobulin-sized molecule (11,800 D) would be significantly greater from blood to dialysate than in the reverse direction, even under conditions of zero net ultrafiltration. CONCLUSION: A novel hollow-fiber dialysis membrane was developed that allows greater convective solute transport from blood to dialysate than from dialysate to blood.     

Pressure Control of Ultrafiltration Rate with High-Flux Dialysis Membranes

Control of ultrafiltration with high-flux dialysis membranes is normally achieved using complex, expensive, volumetric control methods. By using high-flux dialyzers with distensible membranes (parallel-plate dialyzers) in the cocurrent rather than in the countercurrent mode, ultrafiltration can be controlled simply and inexpensively by controlling the outlet pressure differential. Since this is the traditional method of ultrafiltration control, only minor, inexpensive equipment modifications are needed. As expected from transport theory, small molecule clearances are lower with cocurrent than with countercurrent flow. They are, however, adequate and superior to those achieved with post-dilutional hemofiltration (urea clearance > 110 ml/min with cocurrent single-pass, high-flux dialysis). Ultrafiltration control with this method is so simple and predictable that clearances at zero net ultrafiltration rates can easily be measured rather than extrapolated. Since dialysate pressure is always positive, no deaeration systems would be needed in dialysis equipment designed for use with co-current single-pass, high-flux dialysis.     

Protein-leaking membranes for hemodialysis: a new class of membranes in search of an application?

A new class of membranes that leak protein has been developed for hemodialysis. These membranes provide greater clearances of low molecular weight proteins and small protein-bound solutes than do conventional high-flux dialysis membranes but at the cost of some albumin loss into the dialysate. Protein-leaking membranes have been used in a small number of clinical trials. The results of these trials suggest that protein-leaking membranes improve anemia correction, decrease plasma total homocysteine concentrations, and reduce plasma concentrations of glycosylated and oxidized proteins. However, it is not clear yet that routine use of protein-leaking membranes is warranted. Specific uremic toxins that are removed by protein-leaking membranes but not conventional high-flux membranes have not been identified. It is also unclear whether protein-leaking membranes offer benefits beyond those obtained with conventional high-flux membranes used in convective therapies, such as hemofiltration and hemodiafiltration. Finally, the amount of albumin loss that can be tolerated by hemodialysis patients in a long-term therapy has yet to be determined. Protein-leaking membranes offer a new approach to improving outcomes in hemodialysis, but whether their benefits will outweigh their disadvantages will require more basic and clinical research.     

Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells.

BACKGROUND: Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions. METHODS: We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session. RESULTS: Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa. CONCLUSIONS: Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.     

On-line hemodiafiltration. Gold standard or top therapy?

In summary, on-line HDF is an extracorporeal blood purification therapy with increased convective removal of uremic toxins as compared to the most frequently used low- or high-flux HD therapy. The clinical advantages of on-line HDF have shown to be dose dependent, which makes on-line HDF superior to other therapies with less convective solute removal. Among the therapies with high convective solute removal, i.e. on-line HDF, on-line HF and double high-flux dialysis, it is difficult to finally decide on the best therapy, as direct comparisons of these therapies are not performed. Theoretical considerations like the relative to on-line HDF lower achievable Kt/Vurea with on-line HF, allow to state that on-line HDF is the top therapy now available for patients with ESRD. A gold standard may be defined as something with which everything else is compared if one tries to establish it in the respective field. In order to declare on-line HDF as the gold standard in renal replacement therapy, we need more direct comparisons of on-line HDF with other therapies, including mortality as an outcome parameter. However, based on our current knowledge, it does not seem to be too speculative that high-quality clinical studies will establish on-line HDF in the next years as the new gold standard in renal replacement therapy.     

Principles and Practice of Hemofiltration and Hemodiafiltration

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10–15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and β₂-microglobulin (β₂m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.     

Have advances in extracorporeal removal techniques changed the indications for their use in poisonings?

During the past 25 years, numerous changes have taken place in the use of hemodialysis as a therapeutic modality. Advances in technologies and a progression in our collective understanding of the pharmacokinetics of certain xenobiotics have resulted in alterations in the indications, effectiveness, and safety of hemodialysis. However, these changes have not necessarily been reflected in the current published data regarding treatment of intoxications. Reported clearance rates often reflect what was achievable in the 1970s and 1980s, and more recent reports are frequently lacking. Our goal in this review is to summarize the changes in hemodialysis and in other extracorporeal removal technologies and highlight the effects of these changes on the current indications for hemodialysis of the poisoned patient. Changes in dialysis performance that are reviewed in this article include the use of high-efficiency and high-flux dialysis membranes, improved hemodynamic stability because of ultrafiltration control, and the use of bicarbonate as a source of base. We review the indications for hemodialysis for removal of specific toxins, including vancomycin, methotrexate, carbamazepine, and valproic acid.     

Quo vadis Dialysis Membrane?

The development of dialysis membranes is closely related to the development of dialysis as a routine therapy for patients with kidney failure. Without having membranes and dialyzers available as commodity products, the treatment of more than 1 million uremic patients worldwide would be impossible. Several transition periods can be identified: a change in membrane geometry from flat sheet to capillaries, a shift in market appreciation from cellulose to synthetic polymers, and from low-flux to high-flux dialyzers. This shift is supported by the notion that convective therapies using high-flux membranes allow the removal of large-molecular-weight solutes. From a historical background, three eras of perception can be identified for both membrane and dialysis development. First, the period of survival when nephrologists had to focus on techniques for blood access and availability of membranes. Second, the period of issues dedicated to rather specific features of membranes and dialysis therapy such as dose of dialysis, reuse, sterilization, and membrane biocompatibility. And third, the period of quality tops this sequence with a complicated approach: the principal area of interest from the medical community has switched to issues such as quality of life, morbidity, mortality, therapy standards, and cost-effectiveness. New membrane developments should focus on this situation.     

High-Flux Synthetic Versus Cellulosic Membranes for {beta}2-Microglobulin Removal During Hemodialysis, Hemodiafiltration and Hemoflitration

Efficient removal of ß₂ microglobulin (ß₂-M)in end-stage renal failure patients is a continuing preoccupation,as the incidence and severity of dialysis-associated amyloidosisare increasing. To evaluate comparative ß₂-M removalwe studied six stable end-stage renal failure patients duringhigh-flux 3-h haemodialysis, haemodiafiltration, and haemofiltration,using acrylonitrile, cellulose triacetate, polyamide and polysulphonecapillary devices. The reduction of plasma ß₂-M, totalremoval in ultrafiltrate/dialysate, and ß₂-M sievingcoefficients were measured by RIA. The results suggest thatconvection plays the major role in ß₂-M removal whenhigh-flux synthetic membranes are used in combination with highblood flow rates. In contrast, using the cellulose triacetatemembrane under investigation, ß₂-M removal is diminishedwhen ultrafiltration rates are increased. Accordingly, in anyfuture prospective study on the role of ß₂-M retentionin the amyloidogenesis, it is recommended that high-flux syntheticmembranes be employed rather than the type of high-flux cellulosicmembranes used in this study. The modality with which thesesynthetic membranes are used is probably less important, aslong as maximum convective transport rates are obtained. Underpresent conditions, this will imply haemofiltration or haemodiafiltrationrather than haemodialysis.     

Removal of high-molecular-weight solutes during high-efficiency and high-flux haemodialysis

BACKGROUND.: Although urea clearance is often increased during high-efficiencyand high-flux haemodialysis to compensate for short treatmenttimes, the impact of these treatment modalities on the removalof larger uraemic toxins has not been thoroughly investigated. METHODS.: We compared solute removal rates for five haemodialysis treatmentstrategies in vitro using neutral dextrans (molecular radiibetween 15 and 50 Å) as marker macromolecules. Removalrates were assessed by the decrease in dextran concentrationwithin the reservoir of a model circuit using outdated humanplasma as the test solution. Results for high-efficiency haemodialysis(CA 110 dialyser at a blood flow rate of 400 ml/min and TAF175dialyser at a blood flow rate of 300 ml/min) and high-flux haemodialysis(CT190G dialyser at a blood flow rate of 300 ml/min and F60dialyser at a blood flow rate of 300 ml/min) were compared withthose for conventional haemodialysis (CA110 dialyser at a bloodflow rate of 200 ml/min). RESULTS.: Dextran clearances were dependent on the dialyser employed,and they decreased with molecular size and time for each treatmentstrategy. Removal rates were greatest using the CT190G and F60dialysers, intermediate for the TAF175 dialyser, and lowestfor the CA110 dialyser at either blood flow rate. CONCLUSIONS.: The results of this study demonstrate that increasing bloodflow rates alone to increase urea clearance may not provideadequate removal of high-molecular-weight solutes. The use ofhigh-flux or large surface area, high-efficiency dialysers aremore effective in maintaining the removal of high-molecular-weightsolutes when treatment time is shortened.     

Sequential hypertonic haemodialysis in children

Sequential hypertonic dialysis (SHD) was studied in two binephrectomized children over a period of 6 weeks. Each dialysis session comprised four periods of 45 min. The concentration of sodium in the dialysate [Na(D)] during the first period was 190 mmol/l and during the second period 140 mmol/l. The sequence was then repeated. The sodium-free water clearance [C(ONa)] was calculated from the measurements of the ultrafiltrate clearance and of the sodium clearance. Despite the short periods of hypertonic dialysis, C(ONa) was positive, suggesting that water was removed from the intracellular compartment as well as from the extracellular fluid. The transfer of fluid from the intracellular space improved circulatory stability during rapid removal of large volumes of fluid by ultrafiltration. SHD was also associated with increased removal of potassium and phosphate. Comparison of clinical parameters before and during SHD showed a tendency towards increased sodium balance and the possibility of raised cardiovascular morbidity. SHD stabilized blood volume during ultrafiltration, encouraging removal of uraemic toxins. SHD with this levels of Na(D) is only a study dialysis method.     

Clinical manifestations of AB-amyloidosis: effects of biocompatibility and flux.

BACKGROUND: Highly permeable biocompatible dialysis membranes may postpone the development of AB-amyloidosis, but the relative contribution of enhanced flux or reduced inflammation by highly biocompatible membranes and sterile dialysis fluid remains unknown. METHODS: In this retrospective investigation, 89 patients with end-stage renal disease maintained on regular haemodialysis for at least 10 years and treated with one type of dialysis membrane exclusively were selected for analysis. They were divided into three groups: low-flux, bioincompatible cellulose (I), low-flux, intermediately biocompatible polysulphone or PMMA (II), or high-flux, highly biocompatible polysulphone or AN69 (III). In addition, the patients were analysed according to the microbiological quality of the dialysis fluid, which had been tested regularly and was classified either as standard or as intermittently contaminated. The clinical manifestations indicative of AB-amyloidosis, namely, carpal tunnel syndrome, arthropathy and bone cysts, were diagnosed after recruitment. RESULTS: Clinical symptoms were most pronounced in group I, intermediate in group II, and lowest in group III. Patients treated with intermittently contaminated dialysis fluid showed a higher prevalence of AB-amyloidosis than patients with less contaminated dialysis fluid. Logistic regression analysis demonstrated that the flux characteristics of the dialyser and the microbiological quality of the dialysis fluid as well as the biocompatibility of the dialyser were independent determinants of AB-amyloidosis. CONCLUSION: It would be prudent clinical practice to employ high-flux biocompatible membranes in conjunction with ultrapure dialysis fluid for the treatment of end-stage renal disease patients who need to remain on long-term haemodialysis.     

The importance of convective transport

BACKGROUND: Despite technological advances in dialysis equipment and modalities, survival, morbidity, and quality of life of hemodialysis patients are still severely affected by acute intradialytic and long-term complications, possibly related to the treatment itself. Convective treatments, such as high-flux hemodialysis, hemodiafiltration, and hemofiltration are increasingly suggested as further improvements over standard diffusive hemodialysis. The membranes used for these techniques are high-flux semisynthetic and synthetic membranes. Characteristics of these membranes are high permeability, which allows convective removal of water and electrolytes and higher clearance of middle and large molecular weight solutes, and high biocompatibility, which minimizes the "inflammatory response" secondary to interactions between blood and the artificial material of the hemodialysis system. METHODS: With the specific aim of verifying the superiority of convective treatments in reducing morbidity and mortality, we performed a review of the published literature. RESULTS: Some epidemiological studies suggest that convective treatments reduce morbidity and mortality among dialysis patients. However, the results of the published prospective randomized controlled trials are conflicting. Moreover, since convective treatments are usually performed with synthetic biocompatible membranes, it is hard to separate the effect of convection from the effect of biocompatibility. CONCLUSIONS: To finally assess the effect of high-flux membranes on morbidity and mortality, the results of two randomized, controlled clinical trials (HEMO study and MPO study) specifically designed with this aim are needed.     

High Rates of controlled ultrafiltration combined with optimal diffusion: recent advances in hemodialysis technique.

A system which permits high rates of middle molecule removal while preserving the removal of low molecular weight substances is described. It consists of a high fluid flux hollow fiber artificial kidney and an ultrafiltration controller. When used in combination, high rates of convective transport can be achieved through rapid ultrafiltration and reconstitution of blood with physiologic salt solutions. The theoretical impact of changing from conventional dialysis to this form of therapy on the body burden of middle molecules is estimated.     

Blood oxidative stress and lipoprotein oxidizability in haemodialysis patients: effect of the use of a vitamin E-coated dialysis membrane.

BACKGROUND: Oxidative stress has been shown in haemodialysis patients in relation with an increased production of free radicals due to membrane-induced complement and leukocyte activation. In order to minimize membrane bioincompatibility and thereby oxidative stress, more compatible filters have been perfected. Among them, a high-flux vitamin E-coated membrane (CL-EE) has been proposed recently. In vivo, little data is available on the consequences of the use of vitamin E-coated membranes. In the present study, the effects of a 3-month use of CL-EE dialysis membranes compared to conventional membranes have been evaluated in 12 haemodialysis patients on the blood oxidative stress status before and after the dialysis session. METHODS: We determined the lipid peroxidation status (plasma thiobarbituric acid-reactive substances) and antioxidant defence (erythrocyte Cu,Zn-superoxide dismutase and plasma and erythrocyte glutathione peroxidase activities, plasma vitamin E, beta-carotene, vitamin A and total antioxidant status). Also, we simultaneously determined the antioxidant content and the copper oxidizability of isolated low density- and high density-lipoproteins (LDLs and HDLs). RESULTS: The main consequence observed under these conditions was a marked enrichment of plasma with vitamin E, which was also significantly and selectively noted in HDLs (no changes in LDL vitamin E content), perhaps related to a specific storage capacity for vitamin E in HDLs of haemodialysis patients. The beta-carotene content of plasma, LDLs and HDLs was also higher after use of vitamin E-coated membranes than after use of high-flux biocompatible membranes. HDL copper oxidizability was reduced (as shown by an increased lag time) before dialysis after use of CL-EE membranes compared to conventional membranes, whereas LDL oxidizability remained unchanged. CONCLUSION: A 3-month use of vitamin E-coated membranes resulted in a significant increase in plasma and HDL vitamin E content, associated with a lower oxidizability of HDLs, which could be beneficial for haemodialysis patients.