Randomized trial of high-flux vs low-flux haemodialysis: effects on homocysteine and lipids. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study. Effect of dialysis dose and membrane flux in maintenance hemodialysis. Low-flux versus high-flux synthetic dialysis membrane in acute renal failure: prospective randomized study. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. Do high-flux dialysis membranes affect renal dyslipidemia? Effect of high-flux dialysis on the anaemia of haemodialysis patients. Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance. The effect of high-flux hemodialysis on dialysis-associated amyloidosis. High flux dialysis membranes improve plasma lipoprotein profiles in patients with end-stage renal disease. Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery. Are high flux dialysis and erythropoietin treatment in a collision course? Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study. Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients. WHO European Collaborative Trial of multifactorial prevention of coronary heart disease. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients. Systemic cardiovascular response in hemodialysis without and with ultrafiltration with membranes of high and low biocompatibility. Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis. High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients. The multifactor primary prevention trial in Göteborg, Sweden. Effect of acetate-free biofiltration on the anaemia of haemodialysis patients: a prospective cross-over study.
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. Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease.
                Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40-75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality.
                A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0.46 [95% CI 0.27-0.78], p=0.014). Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarction (0.3 [0.11-0.78], p=0.016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected.
                In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction. Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances. A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low-molecular-mass proteins, has a clinical impact.
                In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low-flux haemodialysis (HD; n = 21) or haemodiafiltration (HDF; n = 23). To eliminate confounding factors, low-molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group.
                Morbidity, mortality, blood pressure, dialysis-associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF, beta2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months.
                In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well-dialysed patients with low-flux HD. In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity, on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae. 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 The influence of dialyzer membrane on the morbidity and mortality of patients with acute renal failure remains a matter of debate. The aim of the prospective randomized clinical study was to assess the influence of the flux of a synthetic dialyzer membrane on patients' survival rate, restitution of renal function, and duration of hemodialysis treatment of patients with acute renal failure as a part of multiorgan failure. Seventy-two patients treated in intensive care units of the University Medical Center Ljubljana were randomized according to the dialyzer used throughout the duration of hemodialysis treatment. There were 38 patients in the low-flux group (dialyzer F6, low-flux polysuphone, Fresenius, Bad Homburg, Germany) and 34 patients in the high-flux group (dialyzer Filtral 12, sulphonated high-flux polyacrylonitrile, Hospal, Industrie Meyzieu, France). Both groups were balanced in terms of sex, age, APACHE II score, oliguria before dialysis, cause of acute renal failure, inotropic support, mechanical ventilation, and the number of failing organs. The patients' survival rate was 18.7% in the low-flux group and 20.6% in the high-flux group. Ten patients (26.3%) recovered their renal function in the low-flux group and 8 (23.5%) in the high-flux group. Hemodialysis treatment lasted 11.2 days in the low-flux and 10.7 days in the high-flux group. An analysis of subgroups with a lower mortality rate (subgroup of patients without oliguria and subgroup of patients with less than 4 failed organ systems) did not show significant differences between the low-flux and high-flux groups in terms of survival rate, recovery of renal function, and duration of hemodialysis treatment. In conclusion, no significant differences were found in the results of low-flux versus high-flux synthetic membrane dialyzer treatment in patients with acute renal failure as a part of multiorgan failure in terms of survival rate, recovery of renal function, incidence of oliguria during hemodialysis, and duration of hemodialysis treatment. The number of failing organs seems to be the most important single factor determining the survival of patients with acute renal failure as a part of multiorgan failure. Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial. In this study, we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome.
                Our prospective, randomised, multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France. Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer. 360 patients were randomised, and the primary endpoint was 60-day survival based on an intention-to-treat analysis.
                Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any other time.
                These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis. The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with "mild" hypertension. 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. 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. 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. 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. 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. To assess whether a nurse led, flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital.
                Randomised controlled trial.
                Intensive care unit and cardiothoracic unit of a university teaching hospital.
                174 patients who underwent cardiac surgery between April 2000 and January 2003.
                Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2.
                26 control patients had postoperative complications (two deaths) compared with 17 (four deaths) protocol patients (P = 0.08). Duration of hospital stay in the protocol group was significantly reduced from a median of nine (interquartile range 7-12) days to seven (7-10) days (P = 0.02). The mean duration of hospital stay was reduced from 13.9 to 11.4 days, a saving in hospital bed days of 18% (95% confidence interval -12% to 47%). Usage of intensive care beds was reduced by 23% (-8% to 59%).
                A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay. 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%. Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF).
                The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized.
                After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change.
                No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state. 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. Results are reported from a trial of multifactorial prevention of coronary heart disease (CHD) in occupational groups, involving randomization of 66 factories to intervention and control (49,781 men ages 40 to 59) in the United Kingdom, Belgium, Italy, and Poland. Net average reductions in the intervention factors were 1.2% (plasma cholesterol), 8.9% (daily cigarettes), 0.4% (weight), 2% (systolic blood pressure), and 11% for a combined risk estimate. Reductions were larger in high-risk men (19% for the combined estimate). Red blood cell fatty acid profiles were substantially changed. There was a net overall reduction of 7.4% in fatal CHD and 2.7% in total deaths. Benefits were larger in centers achieving larger risk factor reductions, and in one country--Belgium--the net decreases in CHD incidence and total deaths were significant at the 5% level. Benefit was at least as great in men with established ECG abnormality. It is concluded that CHD risk in middle-aged men seems to be reducible by simple and cost-effective means. We set out to determine if the heparinase-modified thrombelastogram using anticoagulated blood from patients during cardiac surgery could guide treatment with haemostatic components. In 60 patients a simple algorithm predicted a possible 60-80% decrease in the use of haemostatic components. In a second series, 30 patients were allocated to receive components using this intra-operative algorithm and 30 using clinical criteria and laboratory-based tests. Ten patients in the clinical group received a total of 16 units of fresh frozen plasma and nine platelet concentrates compared with five patients transfused with five units of fresh frozen plasma and one platelet concentrate in the algorithm group. Twelve-hour chest tube losses [algorithm group 470 (295-820) ml, clinically managed group 390 (240-820) ml (median, quartile values)] were not different between groups despite the threefold reduction in the use of haemostatic products, showing that intra-operative monitoring of coagulation in the anticoagulated patient can be used to guide treatment. 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. In order to test whether dialyzer membrane biocompatibility influences systemic cardiovascular function, we treated 8 hemodialysis patients (4 men and 4 women, aged 24-73 years) with a low-biocompatible (cuprophane) and a high-biocompatible (polyacrylonitrile) membrane in a randomized double-blind crossover protocol using bicarbonate hemodialysis without ultrafiltration for the first 60 min and with ultrafiltration for the remaining treatment time. Left ventricular function and systemic hemodynamics were assessed noninvasively at baseline and during treatment by Doppler echocardiography combined with external subclavian artery pulse trace calibrated with oscillometrically measured brachial artery blood pressures. There was no significant difference in the cardiovascular response to the 2 membranes, neither during isolated hemodialysis nor when ultrafiltration was added. Mean arterial pressure increased 10% (p < 0.001) during isolated hemodialysis and returned to baseline levels with ultrafiltration. The cardiac index decreased 22% (p < 0.001) during ultrafiltration, due to the greater decrease in left ventricular stroke index (30%, p < 0.001) than increase in heart rate (9%, p < 0.05). Total peripheral resistance increased 10% (p < 0.05) during isolated hemodialysis and a further 19% (p < 0.01) when ultrafiltration was added. Hence, profound cardiovascular alterations were observed during hemodialysis treatment; however, these changes were not related to the biocompatibility of the membranes. 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. 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. The effect of a multifactorial intervention programme on coronary heart disease (CHD), stroke incidence and total mortality was determined in a random sample of men, 47-55 years old at entry. The intervention group comprised 10 004 men, and the two control groups were of similar size. The intervention consisted of antihypertensive treatment in subjects with screening blood pressure above 175 mmHg systolic or 115 mmHg diastolic, dietary advice to men with serum cholesterol levels above 260 mg per 100 ml (= 6.8 mMol l-1), advice to stop smoking to subjects who smoked more than 15 cigarettes per day. The intervention was applied for 10 years during which time CHD and stroke incidence and mortality were followed by means of special registers. Participation rate at first screening examination was 75%. The risk factor levels, i.e. blood pressure, serum cholesterol and smoking decreased markedly during 10 years in the intervention group, but also among the control groups. Total mortality, stroke and CHD incidence did not differ significantly between the intervention group and any of the two control groups. We conclude that a decrease has taken place in all three major risk factors for CHD in the general male population in Göteborg, Sweden. Strategies other than intervention on high-risk individuals must be chosen if a major impact on disease incidence is to be achieved in the general population. The discussion about the pathogenesis of renal anaemia, whether it is primarily due to relative erythropoietin (Epo) deficiency or to uraemic inhibition of erythropoiesis, is still open. Although it has so far not been possible to identify or isolate a substance retained in uraemia with a suppressive action directed specifically against red-cell production, dialysis therapy can improve the effect of both residual endogenous Epo and exogenous rHuEpo. To what extent the mode and/or the dose of dialysis influence Epo efficacy is as yet poorly understood.
                This study was performed as a single-centre trial. The protocol included a run-in period of 4 months followed by a prospective cross-over study including 6 months each of acetate-free biofiltration (AFB) with a high-flux biocompatible membrane and standard bicarbonate dialysis (BD) with a low-flux cellulosic membrane in a random sequence. AFB is a haemodiafiltration technique based on a continuous post-dilution infusion of a sterile isotonic bicarbonate solution. At the start of the run-in period (and for the entire length of the study), rHuEpo administration was withdrawn; patients whose haemoglobin (Hb) levels dropped at a level <8.0 g/dl at one single monthly check, had to be withdrawn from the study. A blood sample was collected every month for the blood gas analysis and for the determination of blood urea nitrogen, serum creatinine, sodium, potassium, calcium, phosphorus, Hb, erythrocyte, reticulocyte, leukocyte and thrombocyte cell counts, mean globular volume and haematocrit. An equilibrated single pool Kt/V(urea)>1.2 was mandatory in both treatment modalities. Serum iron, total iron-binding capacity, and ferritin were checked every 3 months.
                Twenty-three of 137 haemodialysis patients were considered eligible for the trial on the basis of the entry criteria. Of these, 15 volunteered and only 10 completed the study. No significant differences in the haematological indices, in the biochemical parameters assessing body iron stores, or in i.v. iron dosage was observed when comparing AFB with BD treatments. The equilibrated single pool Kt/V(urea) was always >1.2 and in no case was a significant difference observed when comparing AFB with BD treatments. Treatment time was significantly different between the two treatments (262+/-2 min in BD and 249+/-1 in AFB, P<0.0001). Neither pre- nor post-dialysis systolic and diastolic blood pressures, pre-dialysis serum bicarbonate and pH, pre-dialysis serum sodium, potassium, calcium, or phosphorus were significantly different when comparing the two treatment modalities. All 10 patients completed the 1-year follow-up without any major side-effects.
                Our study did not show any improvement of anaemia when treating a highly selected patient group, in the absence of any Epo therapy, with AFB compared with standard BD. Even though these conclusions cannot be extended in toto to the entire dialysis population, in which there is a large proportion of Epo-treated patients with Hb levels around 11 g/dl, we may nevertheless conclude that when patients are well selected, adequately dialysed, and not iron- and/or vitamin-depleted, the effect of a haemodiafiltration technique with a high-flux biocompatible membrane is less than might be expected from the results of uncontrolled studies.
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.