High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.     

Plasma adrenomedullin levels in patients on hemodialysis

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.     

The effect of high-flux hemodialysis on dialysis-associated amyloidosis

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.     

Beta-2-microglobulin in hemodialysis patients. Effects of different dialyzers and different dialysis procedures

beta 2-Microglobulin (beta 2m) has been identified as the major constituent of dialysis-related amyloid. Although there is no clear correlation between absolute beta 2m levels and amyloidosis-related symptoms, elevated serum levels are thought to be the basis for tissue deposition of beta 2m. Besides diminished renal excretion and insufficient removal during hemodialysis, a dialysis-related induction of beta 2m production is discussed as the major cause of elevated serum beta 2m levels. In order to evaluate the influence of hemodialysis membranes and the hemodialysis procedure on beta 2m levels we determined serum beta 2m levels in patients on chronic intermittent hemodialysis. Polymethylmethacrylate 2.0 m2, cuprophane and cellulose acetate dialyzers led to increasing beta 2m levels during dialysis, which was in excess of what could be accounted for by hemoconcentration. The polymethylmethacrylate 1.6 m2 dialyzer did not result in a significant rise of beta 2m levels during dialysis. This indicates that production of beta 2m is not only dependent on the membrane material but also on the surface area of the dialyzer. The use of polysulfone and hemophane low-flux dialyzers did not induce an increase in beta 2m levels during dialysis but a significant clearance of beta 2m was not demonstrable either. Volume-controlled dialysis with high-flux membranes (polysulfone 0.65 m2 and polysulfone 1.25 m2) lowered beta 2m; clearance values, however, were significantly higher when these dialyzers were used in a hemodiafiltration procedure. We conclude from our study that some dialysis membranes appear to induce beta 2m production, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiogenin: a novel inhibitor of neutrophil lactoferrin release during extracorporeal circulation

Degranulation of polymorphonuclear leukocytes (PMNL) occurs during extracorporeal circulation. A degranulation-inhibiting protein identical to angiogenin was recently isolated from high-flux dialyzer ultrafiltrate. This protein inhibits the release of lactoferrin and metalloproteinases from PMNL in vitro. In the present study, we investigated end-stage renal disease patients undergoing regular hemodialysis treatment with either high-flux dialyzers (n = 51) or low-flux dialyzers (n = 44), and chronically uremic patients undergoing hemodiafiltration (n = 30). Hemodialysis therapy with low-flux polysulfone or cellulose triacetate membranes caused no or only minimal reduction (相似文献   

The effect of high-flux hemodialysis on renal anemia

BACKGROUND: Anemia is an important predictor of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Erythropoietin (EPO) is an expensive drug, which increases the cost of therapy. In addition, anemia persists in 20-30% of cases despite EPO treatment. In this study, which depended on the idea that the clearance of moderate and high molecular weight erythropoiesis inhibitors leads to an improvement in terms of anemia, we aimed to investigate the effect of high-flux dialysis on anemia and EPO requirement in patients undergoing HD. METHODS: The study included 48 patients with ESRD on chronic HD treatment who could not reach the target hemoglobin (Hb) level, despite treatment with at least 200 IU/kg/week subcutaneous EPO. Patients were randomized into two groups and HD was performed with polysulphone low-flux dialyzer (Fresenius F6 HPS) or polysulphone high-flux dialyzer (Fresenius F60) for 6 months. RESULTS: Although the EPO doses were significantly lower (p<0.001) in the high-flux dialysis group, Hb levels showed a significant increase (p<0.001). In the low-flux dialysis group, Hb levels showed no significant increase, despite the steady increase in EPO doses. In the high-flux group, the reduction of beta2-microglobulin (b2-MG) and phosphorus levels during dialysis was significantly higher when compared to the low-flux group (p<0.001). During the follow-up period, while b2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). Kt/V(urea) values showed no significant difference throughout the study. CONCLUSIONS: Our results suggest that high-flux dialysis use is effective and this can be an alternative method in terms of controlling renal anemia and reducing the cost of therapy. These beneficial effects of high-flux dialysis are probably mediated by the improved clearance of moderate and high molecular weight toxins.     

Rebound kinetics of beta2-microglobulin after hemodialysis.

BACKGROUND: Evaluation of beta2-microglobulin (beta2m) removal during hemodialysis using predialysis and immediate postdialysis plasma concentrations is only valid in the absence of postdialysis rebound. Postdialysis rebound of beta2m has not been studied extensively, and its importance in the determination of beta2m clearance is unknown. METHODS: We evaluated the kinetics of urea and beta2m in a crossover study of 10 chronic hemodialysis patients using dialyzers with similar urea mass transfer-area coefficients containing either low-flux cellulose acetate or high-flux cellulose triacetate membranes. Kinetics were examined during and following a 210 minute treatment by measuring plasma concentrations predialysis at regular intervals during therapy and at 0, 2, 10, 20, 30, and 60 minutes postdialysis. Clearances of urea and beta2m were also determined directly from the arterial and venous concentration differences across the dialyzer at 60 minutes after starting dialysis. RESULTS: By design, urea removal was similar for both low-flux and high-flux dialyzers as assessed by the urea reduction ratio and Kt/V. Postdialysis urea rebound was similar for low- and high-flux dialyzers; the rebound in the plasma urea nitrogen concentration (expressed as a percentage of the intradialytic decrease in plasma concentration) was 9.2 +/- 1.9% (mean +/- SEM) at 30 minutes postdialysis and 13.0 +/- 1.4% at 60 minutes postdialysis for a single pool urea Kt/V of 1.16 +/- 0.05. The plasma beta2m concentration increased by 11.1 +/- 3.0% during the treatment using the low-flux dialyzer but decreased by 27.1 +/- 4.0% during the treatment using the high-flux dialyzer. When using the high-flux dialyzer, the rebound of beta2m was 44.8 +/- 21.4% at 30 minute postdialysis and 45.9 +/- 15.9% at 60 minutes postdialysis. The clearance of beta2m for the high-flux dialyzer calculated from predialysis and immediate postdialysis plasma concentrations using a single-compartment model (28.2 +/- 4.4 ml/min) was higher (P < 0.05) than that determined directly across the dialyzer (18.3 +/- 2.0 ml/min). If either the 30- or 60-minute postdialysis plasma beta2m concentration was used instead, the calculated beta2m clearance (16. 5 +/- 4.8 ml/min or 15.6 +/- 2.8 ml/min, respectively) was similar to that determined directly across the dialyzer. CONCLUSIONS: Postdialysis rebound of beta2m when using high-flux dialyzers is substantial; neglecting postdialysis rebound results in an overestimation of beta2m clearance when calculated using a single-compartment model.     

高通量血液透析对患者营养状况的影响

目的 研究高通量血液透析对患者营养状况的影响.方法 采用前瞻性、自身对照研究.30例维持性常规低通量血液透析患者,转换为高通量血液透析6个月.试验前(0个月)、试验后3、6个月分别测定白蛋白、胆固醇、铁蛋白水平,计算标准化的蛋白氮出现率相当蛋白质(nPNA),测量瘦体重、握力并进行食欲量表评分.结果 转换为高通量透析后患者白蛋白、胆固醇、铁蛋白浓度比较差异无统计学意义(P<0.05).瘦体重在试验开始0、3、6个月分别为(39.7±8.7)kg、(35.0±6.8)kg、(34.5±1.3)kg,试验前、后比较差异有统计学意义(P<0.05),而握力水平比较分别为(22±10)kg、(25±11)kg、(25±10)kg.nPNA及食欲母表分数在试验前、后比较差异无统计学意义(P>0.05).结论 高通量血液透析会对患者的营养状况产生一定影响.     

Low-flux versus high-flux synthetic dialysis membrane in acute renal failure: prospective randomized study

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.     

Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

Abstract

Background: Following the introduction of modified cellulosic and then synthetic membrane dialyzers, it was realized that the dialyzer bio-incompatibility depends on the membrane composition. We designed a prospective, randomized, cohort study of 6 months to determine several parameters of biocompatibility in maintenance hemodialysis (MHD) patients treated with four different membrane dialyzers. Methods: There were 60 MHD patients enrolled in the study. In baseline, synthetic low-flux dialyzer, polysulfone (PS) membrane was used in all patients for at least 3 months. Then the patients were randomly divided into three groups according to different dialyzer membranes. Synthetic high-flux dialyzer group, ployethersulfone membrane, cellulose triacetate (CTA) high-flux membrane, and synthetic low-flux dialyzer, polymethylmethacrylate (PMMA) membrane were used in 6 months. A new dialyzer was used for each study treatment, and there was no dialyzer reuse. The biocompatibility markers and solutes removal markers were detected repeatedly at different time points. Results: The blood levels of highly sensitive C reactive protein, interleukin (IL)-1β, and interleukin (IL)-13 showed no difference among different groups at al time points. However, the blood complement levels and white blood cell counts were significantly different among three groups. When the dialyzers changed from PS to PMMA membrane, C3a levels and white blood cell counts changed significantly (p < 0.05). Moreover, the changes of C5a levels were significantly different between group CTA and group PMMA in month 3 (p < 0.05). Conclusion: There were much more differences on bio-incompatibility among different dialyzer membranes.     

Impact of hemodialysis membrane and permeability on neutrophil transmigration in vitro

BACKGROUND/AIM: The impact of dialysis membrane permeability on neutrophil transmigration properties in vitro was examined in the present study. This issue has not been fully scrutinized before. METHODS: We studied the capacity of neutrophils collected from a group of dialysis patients randomly treated with cuprophan, low- or high-flux polysulfone, to transmigrate in vitro through a membrane covered with fibronectin (a main constituent of the endothelial basement membrane). The hemodialysis-induced quantitative changes in expression of adhesion molecules were examined in parallel. RESULTS: At the end of dialysis, neutrophils collected from patients treated with high-flux polysulfone dialyzers had a significantly higher transmigration index than neutrophils from patients treated with low-flux polysulfone membrane (p < 0.01) or cuprophan membrane (p < 0.01), and approached the level of transmigration observed in neutrophils collected from healthy controls. In the groups treated with low-flux polysulfone and cuprophan dialyzers, the transmigration capacity was significantly lower (p < 0.02) compared to neutrophils from healthy subjects. We also noted that differences between low- and high-flux polysulfone dialysis, in the context of transmigration properties, were not mirrored by changes in adhesion phenotype, which strengthens the view that there is no strict relationship between these two features. CONCLUSION: The study demonstrates that high-flux polysulfone dialysis, as opposed to low-flux polysulfone and cuprophan treatment, improves the transmigration properties of circulating neutrophils, despite similar effects on adhesion molecule phenotypes. A plausible mechanism is that potentially toxic middle range molecules that inhibit neutrophil migration are more efficiently eliminated during high-flux polysulfone dialysis, but this explanation requires further support.     

高通量透析对维持性血液透析患者中医证候的影响

目的：观察高通量透析（HFHD）对维持性血液透析（MHD）患者中医证候以及营养不良和微炎症状态的影响。方法：采用随机对照,A组应用高通量透析,B组应用普通透析,比较治疗前及治疗后中医证候积分（TCM syndromes cores）,及治疗后血红蛋白（Hb、血浆白蛋白（Alb）、前白蛋白（PAB）、超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、肱三头肌皮皱厚度（TSF）、上臂中段肌肉周径（MAMC）等指标变化。结果：（1）治疗4周、8周后,A组中医实证积分、虚证积分、总积分与治疗前相比有降低趋势,但差异尚无统计学意义（P〉0.05）。12周后与治疗前比较,A组中医证候积分均明显下降（P〈0.05）,B组证候积分与治疗前相比差异无统计学意义（P〉0.05）。治疗12周A组临床疗效优于B组（P〈0.01）。（2）治疗12周时,A组Hb、Alb、PAB明显上升（P〈0.05）,hs-CRP、IL-6、TNF-α水平与治疗前相比明显下降（P〈0.01）,TSF升高（P〈0.01）,MAMC有升高趋势,但差异尚无统计学意义。B组患者Hb、Alb、PAB、hs-CRP、IL-6、TNF-α水平与治疗前相比差异无统计学意义（P〉0.05）,两组治疗12周后,A组IL-6水平低于B组患者（P〈0.05）。结论：HFHD可减少MHD患者中医证候临床积分,改善患者营养不良及微炎症状态。     

The effects of reprocessing cuprophane and polysulfone dialyzers on beta 2-microglobulin removal from hemodialysis patients

To further define the relationship between dialyzer reuse and the removal of beta 2-microglobulin (beta 2M) during dialysis, 26 patients who received hemodialysis were studied. Thirteen patients were dialyzed with conventional cuprophane dialyzers, and thirteen patients were dialyzed with high-flux polysulfone dialyzers. Patients in each group were dialyzed with only new dialyzers during the primary-use phase of the study, and reprocessed dialyzers during the reuse phase. Dialyzers were used six times during the reuse phase. Serum beta 2M levels were measured both predialysis and postdialysis, and adjusted for fluid loss. Dialysis with conventional cuprophane new dialyzers during the primary-use phase of the study resulted in a 3.3% increase in serum beta 2M levels, and a 2.4% increase in serum beta 2M levels during the reuse phase. The difference in the change of the concentration of beta 2M between primary-use and reuse phases was not statistically significant. Dialysis with high-flux polysulfone new dialyzers during the primary-use phase was associated with a decrease of 59.5% in the mean postdialysis concentration of serum beta 2M compared with the predialysis level. A corresponding decrease of 62.6% in serum beta 2M levels was observed after dialysis with high-flux polysulfone reprocessed dialyzers during the reuse phase. These data show no evidence of an adverse effect on the clearance of beta 2M during dialysis from the reuse of dialyzers up to six times. The results confirm previous studies that have reported that high-flux dialysis with polysulfone dialyzers removes substantial amounts of beta 2M, and dialysis with conventional cuprophane dialyzers does not.     

Long-term reduction of plasma homocysteine levels by super-flux dialyzers in hemodialysis patients

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease in chronic hemodialysis (CHD) patients. Treatment with folic acid normalizes total homocysteine (tHcy) in only a minority of the patients. The present investigation has been conducted to study the influence of various dialyzers with different flux characteristics on the reduction of tHcy in the long term. METHODS: Total Hcy, folate, vitamin B6, vitamin B12, and albumin levels were assessed prospectively in 10 patients undergoing HD with high-flux polysulfon (PS; F 60) and 20 patients with super-flux dialyzers (N = 10 PS, F 500S; N = 10 CTA, Tricea 150G). Blood samples were collected before hemodialysis both at the beginning of the study and after 12 weeks. RESULTS: At baseline, all the groups showed similar tHcy levels. During high-flux dialysis, tHcy remained stable. In contrast, during dialysis with both super-flux modalities, tHcy decreased significantly (F 500S week 1, 29.6 +/- 9.9 micromol/L, and week 12, 21.5 +/- 8.5 micromol/L, P = 0.007; Tricea 150G week 1, 24.4 +/- 8.7 micromol/L, and week 12, 15.3 +/- 3.7 micromol/L, P = 0.008). The difference between high-flux and super-flux dialyzers was highly significant (mean: high-flux increase 15.6%, super-flux decrease 33. 3%, P = 0.001). Multivariate analysis showed a significant effect of super-flux dialysis on tHcy (P = 0.001), independently of the previously mentioned variables. CONCLUSIONS: Our findings clearly show that both types of super-flux dialyzers reduced tHcy significantly. As the molecular weight of free homocysteine is less than 268 D, the most likely explanation seems to be the removal of uremic toxins with inhibitory activities against enzymes involved in the extrarenal homocysteine metabolism.     

血浆N-末端脑钠肽前体水平与维持性血液透析患者容量状态无关

目的 测定维持性血液透析患者生物电阻抗与血浆N-末端脑钠肽前体水平透析前后的变化,评价N-末端脑钠肽前体水平在血透患者中血容量评估的应用价值.方法 选取我院血液净化中心30例病情稳定的维持性血液透析患者,留取透析前后血标本测定N-末端脑钠肽前体.应用生物电阻抗(英国BodyStat公司QUADSCAN 4000多频生物电阻抗分析仪)测量透析前后体水量.结果 透析后N-末端脑钠肽前体水平较透析前明显升高[分别为(6 478.93±7 503.48)与(4 692.83±4 290.62) pg/ml,P＜0.01].透析后身体成分监测值较透析前明显降低[(-0.987± 1.451)与(0.964± 1.581),P＜0.01].结论 N-末端脑钠肽前体的血浆水平与维持性血透患者血容量无关.     

A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove bacteria and endotoxin.

Pyrogenic reactions (PR) are a well-recognized complication of hemodialysis and have been associated with dialyzer reuse, high-flux dialysis, and bicarbonate dialysate. However, the roles of bacteria and endotoxin in dialysate for producing PR are not well defined. To determine the effect of removing most bacteria and endotoxin from the dialysate on the incidence of PR, a cohort of chronic hemodialysis patients receiving high-flux, high-efficiency, or conventional hemodialysis at three centers with bicarbonate dialysis fluids that had been filtered with a polysulfone high-flux hemodialyzer was prospectively studied. Unfiltered bicarbonate concentrate had median bacterial and endotoxin concentrations of 479,000 CFU/mL and 39,800 pg/mL, respectively. After filtration of the bicarbonate concentrate at the central proportioner, dialysate had a median 9.2 CFU/mL of bacteria and 17.8 pg/mL of endotoxin. Dialysate filtered at individual proportioning dialysis machines had a median 0.001 CFU/mL of bacteria and 0.19 pg/mL of endotoxin. Nine PR were identified among 303 patients after 28,007 hemodialysis treatments (0.3 PR/1,000 treatments). The rate of PR was similar for the three hemodialysis treatment modalities and for first-use compared with reused dialyzers. Although the PR rate in this study was lower (P = 0.046) than the PR rate of a previous study with unfiltered dialysis fluids (0.7 PR/1,000 treatments), it represents a difference of only 10 PR in over 28,000 treatments. It was concluded that filtration of hemodialysis fluids is efficacious in removing bacterial and endotoxin contamination and can result in a lower incidence of PR in patients receiving high-flux, high-efficiency, or conventional hemodialysis.     

Effects of high-flux hemodialysis on oxidant stress

BACKGROUND: Neutrophil oxygen radical production is increased in end-stage renal disease (ESRD) patients and it is further enhanced during dialysis with low-flux cellulosic membranes. This increased oxygen radical production may contribute to the protein and lipid oxidation observed in ESRD patients. We tested the hypothesis that high-flux hemodialysis does not increase oxygen radical production and that it is not associated with protein oxidation. METHODS: Neutrophil oxygen radical production was measured during dialysis with high-flux dialyzers containing polysulfone and cellulose triacetate membranes. Free sulfhydryl and carbonyl groups and advanced oxidation protein products were measured to assess plasma protein oxidation. RESULTS: Pre-dialysis, neutrophil oxygen radical production was significantly greater than normal and increased significantly as blood passed through the dialyzer in the first 30 minutes of dialysis. Post-dialysis, however, neutrophil oxygen radical production had decreased and was not different from normal. Pre-dialysis, significant plasma protein oxidation was evident from reduced free sulfhydryl groups, increased carbonyl groups, and increased advanced oxidation protein products. Post-dialysis, plasma protein free sulfhydryl groups had increased to normal levels, while plasma protein carbonyl groups increased slightly, and advanced oxidation protein products remained unchanged. CONCLUSIONS: The results of this study show that neutrophil oxygen radical production normalizes during high-flux dialysis, despite a transient increase early in dialysis. This decrease in oxygen radical production is associated with an improvement in some, but not all, measures of protein oxidation.     

血液透析患者应用高通量透析的临床疗效观察

目的 比较高通量透析与低通量透析对透析患者的治疗效果.方法 40例维持性血液透析患者采用自身对照的方法,间断接受高通量透析及低通量透析治疗,总计48周.观察治疗过程中临床症状的改善情况,比较2种透析方式单次透析的效果,以及治疗过程中β2微球蛋白、C反应蛋白、白细胞、血清总补体水平的变化趋势.结果 高通量透析期间临床症状缓解明显,且对β2微球蛋白的清除能力明显优于低通量透析,而对于小分子物质的清除能力比较差异无统计学意义(P＞0.05).治疗过程中患者的C反应蛋白有下降趋势,但无统计学意义(P＞0.05),白细胞、血清总补体水平无明显变化.结论 高通量透析能有效地清除β2微球蛋白,从而改善维持性血液透析患者的临床症状及预后.     

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.     

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.