Effect of high-flux dialysis on the anaemia of haemodialysis patients. Biocompatible membranes preserve residual renal function in patients undergoing regular hemodialysis. Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group. Are high flux dialysis and erythropoietin treatment in a collision course? Effect of dialysis dose and membrane flux in maintenance hemodialysis. Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin. Effect of membrane permeability on inflammation and arterial stiffness: a randomized trial. The effect of high-flux hemodialysis on dialysis-associated amyloidosis. Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors. High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients. High flux dialysis membranes improve plasma lipoprotein profiles in patients with end-stage renal disease. Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites. High-flux hemodialysis postpones clinical manifestation of dialysis-related amyloidosis. Reduction of plasma apolipoprotein-B by effective removal of circulating glycation derivatives in uremia. Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients. Tolerance of hemodialysis: a randomized prospective trial of high-flux versus conventional high-efficiency hemodialysis. Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance. Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis. Randomized trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids. Indices of adequate dialysis in patients hemodialyzed with AN 69 membrane. Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis. Effect of membrane permeability on survival of hemodialysis patients. Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients. Do high-flux dialysis membranes affect renal dyslipidemia?
Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients.
                We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients).
                Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550).
                This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies. Initiation of hemodialysis causes a further decrease of residual renal function (RRF). To assess the impact of the biocompatibility of the dialysis membrane, we performed a prospective randomized investigation in 20 normotensive patients with tubulointerstitial nephritis. The patients were randomly allocated to treatment with either a high-flux polysulfone or cellulose membrane over a period of 12 months. RRF, defined by creatinine clearance and daily urine volume, was found to decrease in both groups of patients after the initiation of hemodialysis. Of the two membranes used, however, the cellulose membrane caused an accelerated decrease of RRF (P < 0.05). The better maintenance of RRF in patients treated with polysulfone membranes was associated with higher Kt/V values and increased hematocrit values (P < 0.05). The pathophysiologic mechanism underlying the more rapid decline of RRF could not be explained by intradialytic hypotension, but may be related to the nephrotoxic effects of inflammatory mediators due to bioincompatibility. Therefore, the use of polysulfone membranes might be preferable in patients with relevant RRF. There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications. Twenty patients treated with human recombinant erythropoietin (EPO) for 9 months were studied. The patients were randomly allocated to high flux (HF) or conventional dialysis (CD). Patients on HF used the F-60 or F-80 dialyzer, with a polysulfone membrane; QB: 470 ml/min; QD: 800 ml/min; t: 127 min; Kt/V: 1.01. Conventional dialysis patients used regenerated cellulosic membranes; QB: 297 ml/min; QD: 500 ml/min; t: 193 min; Kt/V: 1.05. Mean dose of EPO was 103 U/kg for HF patients and 112.4 U/kg for patients on CD. At 9 months, no significant differences were observed in HCT (HF 33.6% vs. CD 33.2%), BUN, serum creatinine, potassium, or phosphorus. Hemoconcentration during dialysis was 12% for HF and 17% for CD. Urea clearance decreased 7% for HF and 9% for CD, while clearance of creatinine, potassium, and phosphorus decreased between 14 and 18% with both treatments. Heparin requirements increased 10% in HF and 16% in CD. Hypertension was similar in both groups. One HF patient withdrew from the study because of hypertension and one HF patient had seizures related to hypertension. Vascular access clotting or hospitalizations were no different. High flux dialysis patients on EPO over a 9 month period did not have any catastrophic complications when HCT was maintained between 30 and 35%. The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain.
                We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer.
                In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients.
                Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.
                Copyright 2002 Massachusetts Medical Society Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels. Both larger molecule removal and dialyzer biocompatibility have been implicated in the high-flux hemodialysis (HD)-associated favorable outcome. In an attempt to delineate the effect of membrane permeability, we performed a randomized, crossover study to compare the inflammatory biomarkers, lipid profile, and aortic pulse wave velocity (PWV) of two dialyzers that are composed of identical membranes but with different flux characteristics.
                Stable patients who had anuria and were on low-flux polysulfone membrane were randomly allocated either to HD with high-flux polyamide membrane (group A; 22 patients) or to HD with low-flux polyamide membrane (group B; 24 patients) for 24 weeks, then they were started on 24 weeks of the alternative HD treatment. Apart from the dialyzer, the dialysis prescription remained unchanged.
                Nineteen patients from group A and 23 patients from group B completed the study. Predialysis beta(2)-microglobulin levels decreased significantly when using the high-flux polyamide membrane. No difference between membranes was observed for serum albumin, high-sensitivity C-reactive protein, fibrinogen, IL-6, triglycerides, HDL cholesterol, LDL cholesterol, and lipoprotein(a) during the study. A significant increase in aortic PWV, a marker of aortic stiffness, was noted after patients switched from high-flux to low-flux polyamide membranes. Similarly, the rate of change in aortic PWV was significantly decreased with the use of the high-flux polyamide membrane.
                Our findings suggest that dialysis with polyamide membranes with different flux characteristics did not modify the inflammatory indices and lipid profile in stable HD patients; however, a seemingly beneficial effect on aortic stiffness was noted for patients who were maintained on high-flux polyamide membrane. Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of beta2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p<0.001). During the follow-up period, while beta2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins. Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility.
                Single-center prospective investigation in parallel design with matched pairs.
                Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible).
                Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted.
                Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media.
                The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF. In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments. A major cause of the morbidity and mortality of patients with end-stage renal disease (ESRD) is related to disorders of large blood vessels, especially coronary heart disease. Atherosclerosis, the most common form of this disease, is known to result from abnormalities in plasma lipoproteins, as well as from factors that damage the vessel wall. Two well-known risk factors for coronary heart disease are elevated plasma concentrations of LDL and reduced concentrations of HDL. This latter disorder is often accompanied by elevated triglycerides. Low HDL and elevated triglycerides are commonly associated with ESRD. Dialysis with high flux membranes differs from conventional dialysis in a number of ways. These include better biocompatibility and increased flux of larger molecules. Although several previous studies had suggested that dialysis with high flux membranes improves plasma lipoprotein profiles, a definitive cross-over designed study to assess the roles of high flux versus biocompatibility in altering lipoprotein profiles had not been done. Preliminary data from such a study are presented. These data confirm the beneficial effects of high flux membranes to reduce plasma triglycerides and suggest that this effect is primarily due to the high flux, and not the biocompatible, feature of the membranes. [corrected] Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG.
                Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG.
                There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment.
                The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin. Amyloidosis due to the retention of beta 2-microglobulin (beta 2-MG) is a frequent complication of hemodialysis (HD). Significant amounts of beta 2-MG can be removed from the body by highly permeable HD membranes, whereas conventional low-flux membranes are impermeable for the molecule. In a prospective and controlled study we investigated whether high-flux HD could delay the onset of dialysis-related amyloidosis (DRA). Twenty patients treated with cuprophane low-flux HD membranes were matched for age and previous time on HD either to continue their HD regimen or to receive HD treatment with high-flux polysulfone membranes. For 6 years each patient was examined for manifestations of DRA once a year or upon individual needs, additionally, serum beta 2-MG levels were monitored. After 6 years of follow-up no clinical signs of DRA were found in any of the patients dialyzed with high-flux polysulfone membranes, whereas 8/10 of the conventionally dialyzed patients had CTS and/or osteoarticular lesions. Serum levels of beta 2-MG were significantly reduced in patients treated with high-flux polysulfone membranes. Patients with diabetes and renal insufficiency (Db/ESRD), a group subject to accelerated atherosclerosis exhibit marked increases in the levels of circulating, glycation-derived reactive substances, termed advanced glycation endoproducts (AGEs). These products have been previously shown to react covalently with apoliprotein B (ApoB) to form AGE-ApoB, a modification that results in delayed low density lipoprotein (LDL) clearance and possibly to dyslipidemia. Because the effect of hemodialysis on AGE removal was shown to be unsatisfactory, based on single intradialytic studies, we examined the effect of long-term hemodialysis therapy on serum AGE-ApoB levels, as well as on total serum ApoB of 25 Db/ESRD patients treated by two types of hemodialysis filters, the Fresenius Inc. F8, as the low flux (LF), or high-flux polysulfone AN69 (HF) for two months using an AGE-specific ELISA. At the end of eight weeks, circulating AGE-ApoB levels were reduced significantly (by 35%) from baseline (P = 0.039) in patients treated by HF compared to a modest 16% reduction noted in patients treated by LF (P = 0.05) N = 12, P = 0.047). Of note, total plasma ApoB was reduced by 27% from baseline (P = 0.02) in patients treated by HF compared to a 6% reduction noted in those treated with LF (P = 0.8). In vitro comparison of AGE mass balance, and mass adsorption by the different filters revealed that the higher efficiency of HF filter was due to greater adsorption. The association of reduced AGE-ApoB levels with a decrease in total circulating ApoB by HF and not by LF dialysis suggests: (1) a causal link between AGE clearance and dyslipidemia in diabetic ESRD, and, (2) that more efficient modes of renal replacement treatment and AGE removal could significantly benefit clinical outcome. The objective was to evaluate the effect of high-flux hemodialysis on quality of life, intra- and interdialytic symptoms and neuropsychological function. The study was double-blind single cross-over with random allocation to order of treatment. The patients were stable adult hospital hemodialysis patients. Both the conventional and high-flux membranes were cellulose acetate, the dialysate was bicarbonate, and dialysate sodium was held constant. The high-flux membrane had an ultrafiltration rate of 15 ml/h/mm Hg transmembrane pressure, a B12 clearance of 88 ml/min and a beta 2-microglobulin clearance of 11.4 ml/min. The values of the conventional membrane were 3.5-5.0, 34-45 and negligible. Each treatment period was 4 months. Twenty-two patients completed both phases of the cross-over. The KT/V value was higher during high-flux than conventional treatment; 1.42 versus 1.27(p < 0.05). There were no differences between high-flux and conventional treatment with respect to quality of life. Symptoms during dialysis were less severe during high-flux than conventional treatment for 12/14 items. Only 3 items reached statistical significance (0.05 > p > 0.01) and none were clinically significant. Symptoms between dialyses were less severe during high-flux than conventional treatment for 18/20 items. No single item had a statistically significant improvement but 3 had clinically important improvement. Among the 23 neuropsychological variables, none demonstrated statistically significant changes. Hemodialysis is frequently complicated by hypotension and associated symptoms. It has been suggested that these symptoms may be related to the biochemical changes caused by cellulosic dialysis membranes. In this study, a prospective randomized crossover trial was conducted comparing the incidence of hypotension and acute symptoms during dialysis with large-surface-area (1.6 m2) cellulosic (cuprophane [CUP]) and noncellulosic (polyacrylonitrile [PAN], AN69) membranes. Dialyzers were used for a single use only. There was no difference in predialysis BUN, predialysis blood pressure, intradialytic weight gain, blood flow, dialysis efficiency (urea reduction), dialysis duration, hematocrit, or erythropoietin dose between the two study phases. When these clinical characteristics were matched, there was no difference in the number of episodes of hypotension (CUP, 19 +/- 3; PAN, 22 +/- 3; P = not significant [NS]). The incidence of symptomatic hypotension, as reflected by the number of episodes of hypotension requiring more than 100 mL of saline for correction, was also not different between study phases (CUP, 10 +/- 1; AN69, 11 +/- 2; P = NS). The incidence of intradialytic symptoms, including emesis, cramping, headache, angina, pruritus, and bronchospasm, was similar during the two study phases (CUP, 11 +/- 2; AN69, 10 +/- 1; P = NS). It was concluded that noncellulosic membranes do not offer any significant advantage over cellulosic membranes in reducing the acute complications of hemodialysis. Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking.
                40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study.
                A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03).
                For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.
                Copyright 2008 S. Karger AG, Basel. We studied the influence of different modes of hemodialysis (HD) on plasma levels of beta 2-microglobulin (P-beta 2-m) and its correlation to changes in leukocyte count, complement activation (C3a), and elastase generation. The influence of dialyzer membrane, membrane surface area, duration of treatment, and blood flow was analyzed with respect to post-HD levels of P-beta 2-m. Twenty patients underwent 12 modes of bicarbonate hemodialysis in random order (n = 252) using three different membranes (Cuprophan [CU], hemophan [HE], or polyamide [PA], two dialyzer areas, and fast (400 mL/min) or slow (200 mL/min) blood flow (Qb) for 2 or 4 hours, respectively. All dialysate was collected and beta 2-m was analyzed (D-beta 2-m). After correction for hemoconcentration, P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes (CU, 0.9 +/- 0.3 mg/L, P = 0.002; HE, 1.2 +/- 0.3 mg/L, P < 0.001; and PA, 8.3 +/- 0.3 mg/L, P < 0.001). Elimination of P-beta 2-m was influenced by type of membrane (P < 0.001) and ultrafiltration volume (P = 0.0019) but not by membrane area or Qb. The largest reduction in P-beta 2-m (-10.4 mg/L) was achieved by the following treatment combination: PA membrane, large dialyzer area, and low Qb for 4 hours. P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours (-9.9 +/- 0.5 mg/L) than during high Qb for 2 hours (-6.8 +/- 0.5 mg/L, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) Uncontrolled studies have found that high-flux haemodialysis favourably modifies homocysteine and lipid profiles. We sought to confirm these findings by carrying out a randomized prospective comparison of high-flux and low-flux polysulphone in chronic, stable dialysis patients.
                Forty-eight patients were randomly assigned to either high or low-flux dialysis for 3 months. Serum levels of homocysteine, lipoprotein (a), and lipids were compared between the treatment groups at monthly intervals.
                All patient characteristics and laboratory variables were equally distributed between the groups at baseline. Over the study duration, we observed no differences between high- and low-flux treatment groups for the following outcomes: pre-dialysis homocysteine, lipoprotein (a), total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides (all P>0.05). Geometric mean (interquartile range) homocysteine at baseline was 20.0 (16.8-24.5) and 19.5 (15.3-22.0) micromol/l for the high-and low-flux groups respectively (P=0.80), and levels did not change significantly during the study. We did demonstrate a more pronounced intradialytic effect of high-flux dialysis on homocysteine levels, which fell during dialysis by 42%, compared to 32% with low-flux dialysis (P<0. 001).
                In this randomized controlled trial, the effects of high-flux and low-flux haemodialysis on homocysteine and lipid profiles were comparable. The greater intradialytic effect of high-flux dialysis on homocysteine did not translate into a significant difference in pre-dialysis levels after 3 months of study. The objective of this study was to evaluate the incidence of morbidity (at least one hospitalization) during the first twelve months of hemodialysis (thrice weekly for 4 hours) in 54 (27 males and 27 females) sex and age matched patients, of whom 32 were treated with AN 69 (M/F = 13/19, 62 +/- 14 years) and 22 with Cuprophan (M/F = 14/8, 61 +/- 14 years). Patients were classified according to the value of TAC urea during the period under study: constantly superior or equal to 20 mmol/liter in Group A (high TAC urea) or inferior to 20 mmol/liter in Group B (low TAC urea). Dialysis quantification (Kt/V) and estimation of the patient's protein catabolic rate (PCR) were based on measurement of the midweek pre- and post-dialysis blood urea nitrogen. In the patients of Group B, incidence of morbidity was significantly increased when age was over 50 years and when AN 69 membrane was used (P < 0.02). Furthermore, in Group A, the risk of hospitalization was significantly higher in patients treated by Cuprophan than in those treated by AN 69 (P < 0.02). The survival rate was also studied. Better survival (70%) at four years was observed in patients with high TAC urea who were treated by AN 69. The difference was highly significant with the survival rate (22%) in patients with high TAC urea who were treated by Cuprophan (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) Renal anemia significantly affects the morbidity and mortality of dialysis patients. The aim of the present study was to establish whether the severity of anemia and success of its treatment differs when using high-flux (HF) or low-flux (LF) hemodialysis. Twenty-five patients on long-term hemodialysis with a mean hematocrit (Hct) of 33%, S alb of 36 g/L, and Kt/V urea of 1.5 were divided into Groups X (n = 13) and Y (n = 12) in a prospective randomized crossover study. Group X was initially treated with LF hemodialysis to be followed by HF hemodialysis for 8 weeks each time. Group Y started with 8 week HF hemodialysis and continued, after crossover, with 8 weeks of LF hemodialysis. HF and LF hemodialysis were performed with polysulfone dialyzers F 7HPS and F60S (Fresenius Medical Care, Bad Homburg, Germany). Hct values, examined at 2 week intervals, did not differ significantly between Groups X and Y during 16 weeks of the study at any measuring interval. In another analysis, all results of HF hemodialysis (first 8 weeks of Y + second 8 weeks of X) were pooled as were all data of LF hemodialysis (first 8 weeks of X + second 8 weeks of Y). No significant relationships were noted between duration of treatment with HF hemodialysis and Hct (n = 72, rS = 0.11, p = 0.36) and between duration of LF hemodialysis and Hct (n = 74, rS = 0.02, p = 0.87) in the newly formed groups. The Hct measured during HF hemodialysis and LF hemodialysis did not differ significantly. Analysis of variance did not reveal a relationship between Hct and the HF or LF membrane. As HF and LF hemodialysis differed significantly in Kt/V urea, the variables were adjusted to identical Kt/V urea using analysis of covariance. No relationship between Hct and dialysis membrane permeability was demonstrated even in this case. Use of biocompatible LF and HF membranes in standard hemodialysis modes under conditions of adequate dose of dialysis and the time period studied did not result in different effects on anemia. The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis. 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.
                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.
                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.
                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. High-flux hemodialysis has been reported to attenuate renal dyslipidemia. To evaluate the contribution of dialysis membrane composition per se, we compared the impact on the lipoprotein profile of hemodialysis (HD) with a conventional cellulose dialysis membrane with that of a synthetic high-flux dialysis membrane in standard hemodialysis mode. Forty-two patients (24 men, 18 women; mean age, 69 years; range, 39-85 years) on maintenance HD with cellulosic dialysis membranes were randomized and stratified for diabetes mellitus to 12 weeks of HD treatment with either a cellulose acetate (CA; n = 23) or polyacrylonitrile (AN69; n = 19) membrane. HD was performed in a conventional low-flux standard HD mode 4-6 hours/session. Plasma levels of lipids (TC, TG), apolipoproteins (A-I, B, C-III, E), lipoprotein (a) (Ip(a)), and individual apoA and apoB containing lipoproteins (LP-A-I, LP-A-I:A-II, LP-B, LP-Bc) were determined. At baseline, the AN69 group had slightly higher plasma concentrations of apoC-III and C-III/HS, but there were no other differences at entry in study variables between the treatment groups. Twelve week treatment with an AN69 membrane did not result in any significant changes in lipoprotein profile compared with treatment with a cellulose acetate membrane. HD with AN69 dialysis membranes in the conventional low-flux standard hemodialysis mode does not affect the lipoprotein profile.
High-flux haemodialysis may reduce cardiovascular mortality in people requiring haemodialysis by about 15%. A large well-designed RCT is now required to confirm this finding.