Pyrogenic reactions in patients receiving conventional, high-efficiency, or high-flux hemodialysis treatments with bicarbonate dialysate containing high concentrations of bacteria and endotoxin.

High-efficiency (HE) and high-flux (HF) hemodialysis are becoming increasingly popular methods for treating patients with chronic renal failure because they reduce the time required for dialysis treatment. HF and HE dialyzers require bicarbonate dialysate, often prepared from concentrates that can support bacterial growth with endotoxin production. There is a concern that endotoxins or bacteria may cross or interact at the membranes of these dialyzers, triggering the release of endogenous pyrogens (cytokines) by peripheral blood mononuclear cells to cause pyrogenic reactions (PR). To determine the incidence of PR and to examine the association between PR and levels of bacteria and endotoxin in dialysate, a cohort of patients receiving conventional, HE, or HF hemodialysis with bicarbonate dialysate and reprocessed dialyzers at three dialysis centers during a 12-month period was studied prospectively. All dialyzers underwent a test of membrane integrity before use. A total of 19 PR were identified among 18 patients in 26,877 hemodialysis treatments (0.7 PR/1,000 treatments). There was no significant difference in PR rates by treatment modality: conventional, 0.5 per 1,000 (7 PR/13,123 treatments) versus HE, 0.9 per 1,000 (9 PR/11,345) versus HF, 1.2 per 1,000 (3 PR/2,409) (P = 0.21; chi 2 test). Throughout the study period, bacterial counts for dialysate at each center significantly exceeded the Association for the Advancement of Medical Instrumentation's (AAMI) microbiologic standards for dialysate of less than 2,000 CFU/mL (mean, 19,000 CFU/mL), but water used in the reuse of dialyzers tested less than 200 CFU/mL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microbial and Endotoxin Contamination in Water and Dialysate in the Central United States

The purified water supplies and randomly selected dialysates of 51 chronic and acute dialysis centers in the central United States were surveyed to assess the relative risks to dialysis patients from microbial and endotoxin contamination. A culture medium more sensitive than those generally employed in routine quality assurance assays was used for recovery of bacteria from water. With this medium, 35.3% of the water samples and 19% of the dialysate samples were out of compliance with the Association for the Advancement of Medical Instrumentation (AAMI) standards: 200 and 2,000 colony forming units (CFU)/ml, respectively. There was no correlation observed between the type of water purification system or the frequency of disinfection of the system and the bacterial and endotoxin contamination levels. There was also no correlation found between the bacterial and fungal CFU per ml and the endotoxin concentration per ml (EU/ml). It is recommended that more sensitive culturing methods be used to provide adequate bacterial monitoring of dialysate center water supplies. Dialysis centers should monitor endotoxin in dialysate on a regular schedule and immediately after any endotoxemic-like patient reactions. Yeast and fungi were observed in 10% and 64% of the water systems, respectively. Dialysate was contaminated by yeast and fungi in 30% and 70% of the centers, respectively. The concentrations of these microbes in both fluids were much lower than bacteria. However, they were observed often enough to warrant further investigation of their impact on the well-being of dialysis patients.     

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.     

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests

It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200 ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 +/- 4 ml/min fell progressively to 112 +/- 18 (P less than 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 +/- 2 vs. 226 +/- 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers.     

Ultrapure dialysate

To prevent pyrogenic reactions during hemodialysis, it is recommended that bacteria and endotoxin in dialysate not exceed 100-200 colony forming units (CFU)/ml and 0.25-2 endotoxin units (EU)/ml, respectively. While these limits are adequate to prevent acute pyrogenic reactions, data are accumulating to suggest they may not prevent stimulation of chronic inflammation in hemodialysis patients. Fragments of endotoxin and other bacterial products capable of stimulating immune cells cross low-flux and high-flux membranes in vitro. In clinical studies, use of ultrapure dialysate (bacteria < 0.1 CFU/ml and endotoxin < 0.03 EU/ml) is associated with lower concentrations of inflammatory markers and acute phase reactants than are observed with dialysate meeting current quality recommendations. Moreover, observational studies suggest a link between clinical outcomes and dialysate purity. Treatment of patients with ultrapure dialysate is reported to improve nutritional status, increase responsiveness to erythropoietin, slow the decline in residual renal function, lessen cardiovascular morbidity, and decrease the incidence of beta(2)-microglobulin amyloidosis. To date, however, none of these studies has shown a cause-and-effect relationship between dialysate purity and outcome. Further, there are no data defining the concentration dependence of outcomes on dialysate purity and the relative importance of dialysate purity as a trigger of inflammation remains unclear. While the technology exists to routinely provide ultrapure dialysate, controlled clinical trials are still needed to answer the question of whether or not introducing ultrapure dialysate into routine clinical practice represents an efficient use of limited resources in terms of decreasing inflammation and improving outcomes in hemodialysis patients.     

Ultraviolet irradiation to preserve high reverse osmosis water quality

AIMS: The use of ultrapure dialysate decreases hemodialysis patients' morbidity. Bacterial and endotoxin content of reverse osmosis (RO) water is usually lowered or eliminated by a combination of bacterial filtration and regular disinfection of the distribution. Whether bacterial filtration may be replaced by UV irradiation is unknown. MATERIALS AND METHODS: One, and subsequently two UV lamps were inserted in a complex RO water distribution circuit, devoid of bacterial filters. RO water bacterial content was checked weekly between RO water distribution disinfections. RESULTS: With one UV lamp on the departure of the RO water circuit, bacterial results remained negative (< 1 cfu/ml) till the second week after disinfection. Disinfection of the circuit was required every four weeks to comply with the AAMI Guidelines (< 200 cfu/ml). Failure of the lamp was followed by bacterial growth (up to 500 cfu/ml), promptly aborted after replacement of the failed lamp. Subsequent addition of a second UV lamp on the return line of the water circuit kept bacteria < 1 cfu/ml for up to five weeks. Endotoxin levels remained < 0.125 EU. CONCLUSIONS: UV irradiation preserves a low RO water bacterial/endotoxin content in the distribution line and is not associated with a measurable endotoxin increase.     

Outbreak of gram-negative bacteremia and pyrogenic reactions in a hemodialysis center

During the period from April 4, 1988, to April 20, 1988, nine pyrogenic reactions and five gram-negative bacteremias occurred in 11 patients undergoing dialysis. All pyrogenic reactions and gram-negative bacteremias occurred among patients in whom a reprocessed dialyzer was used. The rate of pyrogenic reactions or bacteremias per 100 sessions using a reprocessed dialyzer was higher than in sessions during which a new dialyzer was used (4.5 vs. 0; p = 0.03). Dialyzers were manually reprocessed with 2.5% Renalin germicide. The Renalin concentrations varied widely in 12 dialyzers stored after manual reprocessing during the epidemic period (0.9-4.2%); the median endotoxin concentrations varied from 0 to 246 ng/ml and were higher in dialyzers with Renalin concentrations less than or equal to 1.0% than in dialyzers with higher concentrations (p = 0.01). Experiments using a dilution technique described by a technician resulted in Renalin concentrations ranging from 1.4% at the surface to 3.5% at the bottom of the preparation container. These findings suggest that failure to adequately admix Renalin during dilution may be associated with low levels of disinfectant, high levels of bacteria and endotoxins in dialyzers, and outbreaks of pyrogenic reactions and gram-negative bacteremias in dialysis patients.     

Quality of water used for haemodialysis: bacteriological and chemical parameters.

BACKGROUND: The bacterial and chemical contamination of dialysate fluids are important problems in haemodialysis therapy and may be caused by the water used for dialysate preparation. METHODS: We performed a survey of the microbiological and chemical quality of the water used in seven dialysis wards. Special attention was paid to the effects of each water treatment step, for example ion exchange, reverse osmosis and UV disinfection, on the number of bacteria (measured as colony forming units, CFU), the amount of endotoxin (endotoxin units, EU) and various chemical parameters, the main focus being on calcium, magnesium, sulphate, aluminium and heavy metals. RESULTS: CFU values exceeding the European Pharmacopeia value, determined at an incubation temperature of 22 degrees C, were found in the samples of raw water (20.0%, n=25), after ion exchange (66.7%, n=12), after reverse osmosis (33.3%, n=18) and also in samples of the dialysis water taken at the inlets (12.5%, n=40) and outlets (50.0%, n=18) of the machines. Whereas all raw water samples from the wards showed high mean values for endotoxin (0.56-9.10 EU/ml) and the endotoxin levels were often enhanced after ion exchange (0.13- >9.49 EU/ml), treatment by reverse osmosis led to a satisfactory decrease in endotoxin in all samples (<0.03 EU/ml). Sufficient reductions in calcium, magnesium and sulphate could only be achieved by the combined application of ion exchange and reverse osmosis. Mercury contamination was observed in the samples after ion exchange at three treatment plants, this was possibly caused by polluted regenerants. Increased amounts of aluminium, copper and zinc were found in water samples from different sites in the treatment systems and were caused by materials in contact with the water. CONCLUSIONS: A sufficient chemical water purification treatment system should consist of ion exchange and reverse osmosis. Attention has to be paid to the suitability of materials in contact with the water and of the chemicals used, for example regenerants or corrosion inhibitors. From the microbiological point of view, a safety UV disinfection step in the water-treatment system is favourable. To avoid bacterial recontamination periodic cleaning and disinfecting of the water-treatment and distribution systems, as well as the dialysis machine are essential. There is the need for complete guidelines regarding dialysis water that include all relevant chemical and microbiological parameters. Based on this standard, periodic examination of the water after each treatment step has to be performed.     

Bacteria and endotoxin removal from bicarbonate dialysis fluids for use in conventional, high-efficiency, and high-flux hemodialysis

The use of bicarbonate-based dialysis fluids in hemodialysis centers in the United States has increased with the advent of high-efficiency and high-flux hemodialysis. However, bicarbonate dialysis fluids can support rapid bacterial growth and high endotoxin concentrations. This study determined the efficacy of an ultrafiltration device in reducing the bacterial and endotoxin concentrations in bicarbonate dialysis fluids. A polysulfone hollow fiber dialyzer was used to ultrafilter bicarbonate concentrate before entering the central proportioner and bicarbonate dialysate after exiting the proportioner in single patient dialysis machines. Pre- and post-ultrafilter samples were collected for bacterial and endotoxin assays over 10 months. Ultrafiltration of bicarbonate concentrate reduced bacterial and endotoxin concentrations from 288,330 colony forming units (CFU)/ml and 42,804 pg/ml to 0.47 CFU/ml and 109 pg/ml, respectively. Ultrafiltration of the dialysate in single patient systems decreased bacterial and endotoxin concentrations from 15,889 CFU/ml and 1,746 pg/ml to 0.003 CFU/ml and 0.109 pg/ml, respectively. These results demonstrate that ultrafiltration of bicarbonate dialysis fluids is effective in reducing bacterial and endotoxin contamination inherently associated with the use of bicarbonate-based dialysates.     

Net Ultrafiltration May Not Eliminate Backfiltration During Hemodialysis with Highly Permeable Membranes

Backfiltration of dialysis solution can occur during hemodialysis with highly permeable membranes. A method has recently been developed for determining backfiltration rates in vitro at low dialysate flow rates by measuring changes in the local dialysate concentration of a marker macromolecule via sampling ports added to the hemodialyzer housing. In the present study, the influence of net ultrafiltration on backfiltration rates was determined for five commercial dialyzers containing membranes with different water permeabilities. In vitro experiments were performed (n = 3) using freshly donated whole blood at blood flow rates of 200 and 340 ml/min and at a dialysate flow rate of 100 ml/min. At zero net ultrafiltration, backfiltration rates increased with increasing membrane water permeability and ranged from 0.9 to 6.9 ml/min. At a net ultrafiltration rate of 10 ml/min, backfiltration was eliminated for dialyzers containing membranes with water permeabilities of less than 30 ml/h/mm Hg but remained significant for dialyzers with higher membrane water permeabilities. Therefore, despite a significant net ultrafiltration rate, backfiltration may still occur during hemodialysis with highly permeable membranes.     

提升透析液水质改善维持性血液透析患者微炎性反应状态

目的 探讨改善透析液水质对长期血液透析患者微炎性反应状态的影响.方法 以53例维持性血液透析(MHD)终末期肾病患者为对象,前瞻性观察透析液水处理系统升级前后患者病情变化.以脱离血液透析(死亡、转为腹膜透析或肾移植)和(或)生存至入组后8年为观察终点.比较水处理系统升级前后透析液内毒素含量及患者血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、白蛋白水平等的变化.结果 水处理系统和中央供液系统经高频热消毒结合内毒素过滤器升级改造后,与升级前比较,透析液内毒素年平均值显著下降[(0.046±0.012) EU/ml比(0.454±0.002) EU/ml,P＜0.01],并在观察期间内维持稳定水平;患者的血清IL-6显著下降[(3.947±3.624) ng/L比(13.779±7.106) ng/L,P=0.036];血清TNF-α显著下降[(7.935±3.864) ng/L比(12.804±8.017) ng/L,P=0.012];血清CRP年平均值显著下降[(0.194±0.149) mg/L比(0.561±0.309) mg/L,P＜0.01],并在观察期间内维持稳定水平;血清白蛋白年平均水平显著增加[(41.900±6.803) g/L比(38.140±7.083) g/L,P=0.042];患者的年平均血红蛋白水平无显著改变,但红细胞生成素应用剂量显著下降[(93.0±12.7)U·kg-1·周-1比(131.0±10.1)U·kg-1·周-1,P=0.015].结论 采用含双级反渗、高频热消毒以及内毒素过滤器在内的水处理和中央供液系统,能明显提升透析液水质.透析液水质提升显著改善了MHD患者的微炎性反应状态及减少相关并发症的发生.     

An Economical New Process for Incenter Bicarbonate Dialysate Production: Comparison with Acetate in a Large Dialysis Population

It is generally agreed that bicarbonate dialysate is preferable to acetate dialysate, but the major limiting factors of high cost and technical difficulty in maintaining its stability for prolonged periods preclude its widespread use. The procedure developed by the authors stabilizes bicarbonate dialysate for up to 4 days, rendering bicarbonate dialysate feasible for routine out-patient use. HCO3 dialysate is produced in our dialysis unit after an initial investment of $10,000.00, at a cost per 4-h treatment of $1.22 at a dialysate flow of 500 cc/min. One hundred fifty-one chronic dialysis patients participated in an 18-week study to evaluate clinical symptomatology when bicarbonate was substituted for acetate as the dialysis base buffer. Evaluation of each dialysis treatment (total of 8,183 treatments) consisted of both subjective and objective criteria (vomiting, angina, cramps, hypotension, and frequency of use of mannitol, hypertonic saline, and nitroglycerine). The patients were unaware of the change in dialysate solutions. There was a significant reduction (p less than 0.001) in the incidence of vomiting, cramps, hypotension, nausea, flushing, and the use of mannitol and hypertonic saline during bicarbonate dialysate treatment compared with acetate dialysate. Shortness of breath, angina, mental confusion, and paresthesias were not statistically changed. Although the method of HCO3 dialysate production is associated with occasional higher bacterial count than currently recommended by AAMI standards, no adverse reactions were observed in patients treated with standard efficiency dialyzers. It is concluded that the process for incenter HCO3 production is safe, economical, and better tolerated than acetate dialysate.     

Bacteriology of Hemodialysis Fluids: Are Current Methodologies Meaningful?

Reports of increasing endotoxic reactions in dialysis centers using high-flux dialyzers and high contamination in liquid bicarbonate concentrates have resulted in concern for the microbial contamination of dialysate. The influence of salt-supplemented media on the recovery of bacterial contaminants from the fluids used in hemodialysis has been examined. This study found a negative influence of a 2% NaCl supplementation of growth media for both purified water and dialysate. Salt-supplemented pour plate cultures of bicarbonate concentrate samples were not statistically different from nonsupplemented cultures (p = 0.2). The influence of the bicarbonate salt on recovery in the pour plates was not addressed. The different media recommended for monitoring microbial contamination of dialysis fluids were compared. As previously reported, both water and dialysate collected from a relatively large geographic area showed higher recoveries on Reasoner's R2A agar than on media recommended by the Association for Advancement of Medical Instrumentation (AAMI) standards (p < 0.0001). Standard methods agar (SMA) and trypticase soy agar (TSA) produced the next highest recovery for water and dialysate, respectively. The higher recoveries generally observed on R2A or SMA suggest that to provide better patient safety these media should be selected for monitoring bacterial contamination of water, and R2A, SMA, or TSA for dialysate. The variability in the species identified across the three fluids and variability in counts observed in the different fluids suggest that significant dialysate contamination may occur from sources other than the water and bicarbonate concentrates.     

The Effects of Endotoxin–Contaminated Dialysate and Polysulfone or Cellulosic Membranes on the Release of TNFα during Simulated Dialysis

Abstract: Simulated dialysis of whole blood was used to determine whether membrane factors (biocompatibility), endotoxin (ET) membrane diffusion, or transmembrane monocyte–ET interactions would stimulate tumor necrosis factor (TNFα) release. Whole blood containing EDTA and aprotinin was recirculated in the blood compartment of hollow fiber dialyzers containing either regenerated cellulose or polysulfone membranes. ET–free and ET–spiked dialysate were recirculated consecutively in the dialysate compartment for 30 min each. Blood and dialysate samples were collected at t _o and after each 30 min of simulated dialysis for determination of TNFa and ET concentrations. TNFa was not detected in any blood samples collected after simulated dialysis with regenerated cellulose (RC) membranes and ET–free or ET–spiked dialysate. However, blood ET concentrations, as determined by the Limulus amebocyte lysate (LAL) assay, increased in RC dialyzers after each 30 min of simulated dialysis even with ET–free dialysate. Since TNFa was not detected in these blood samples, the material detected by the LAL assay probably was not ET but an LAL–reactive material. After simulated dialysis with polysulfone dialyzers and ET–free dialysate, TNFa and ET were not detected in blood samples. ET also was not detected in blood samples after dialysis with ET–spiked dialysate. However, TNFa was detected in 7 of 13 (54%) of the blood samples following the 500 ng/ml of ET dialysate spike. TNFα release during simulated dialysis with polysulfone membranes and ET–contaminated dialysate may be due to transmembrane stimulation of circulating mononuclear cells and not diffusion of ET across the membrane.     

Prevention of biofilm formation in dialysis water treatment systems

BACKGROUND: Biofilm formations in dialysis systems may be relevant because they continuously release bacterial compounds and are resistant against disinfection. The aim of the study was to compare the development of biofilm between a water treatment system based on a single reverse osmosis unit producing purified dialysate water [bacterial count, 350 colony-forming unit (CFU)/L] (center A) and a water treatment system based on double reverse osmosis and electric deionization, which is continuously disinfected with ultraviolet light and treated with ozone once a week (bacterial count, 1 CFU/L) (center B). METHODS: During a period of 12 weeks, biofilm formation was studied in the tubing segment between the water piping and the dialysis module, using four dialysis monitors in each center. On a weekly basis, tubing samples of 5 cm length (N = 96) were taken under aseptic conditions and investigated for microbiologic contamination [cystine lactose electrolyte-deficient (CLED) Agar], endotoxin levels [limulus amoeben lysate (LAL) gel test, cutoff value, 0.0125 EU/mL], and biofilm formation [electron scanning microscopy (SEM)]. RESULTS: In center A, tube cultures were positive (>100 CFU/mL) in 16% of samples at 22 degrees C and 37 degrees C, compared to 3% of samples of center B (P < 0.05; chi-square). Endotoxin levels were positive in 76% of the tubing samples of center A and negative in all of the samples of center B (P < 0.05). Biofilm was present in 91.7% of the samples of center A (Fig. 1), and only present in one sample (taken after 9 weeks) of center B (P < 0.05) (Fig. 2). In center A, biofilm formation was already observed after 1 week. CONCLUSION: In contrast to a standard water treatment system producing purified water, the use of a system producing highly purified water, which is also treated with regular disinfection procedures, leads to a significant reduction in biofilm formation, bacterial growth, and endotoxin levels in a highly vulnerable part of a water treatment system.     

Endotoxin transfer through dialysis membranes: small- versus large-pore membranes.

In this in-vivo study, dialysate and serum endotoxin was evaluated before and after haemodialysis with small-pore (PS400) and large-pore (PS600) polysulphone dialysers, and before and after haemodiafiltration with the PS600 filter. The source of the endotoxin was the presence in dialysate of Pseudomonads at a concentration of 10(3)-10(4) CFU/ml. Endotoxin was measured by a modified chromogenic limulus amoebocyte lysate (LAL) assay. In spite of dialysate endotoxin concentrations greater than 100 pg/ml, no changes in pre- versus posttreatment LAL reactivity were observed in PS400 dialysis and PS600 haemodiafiltration. In contrast, PS600 haemodialysis was related to an increase in serum LAL reactivity from 1.3 +/- 1.5 to 3.8 +/- 2.0 pg/ml (n = 15, P less than 0.01), and five patients (33.3%) showed a post-dialysis value in excess of 5 pg/ml. Our data are consistent with the absence of in-vivo endotoxin transfer during haemodialysis with small-pore dialyser membranes, and during haemodiafiltration with membranes with larger pores. An increase in LAL reactivity during haemodialysis with membranes with larger pores is, however, present, presumably due to the occurrence of backdiffusion/filtration with that specific strategy.     

Ultrapure Dialysate for Home Hemodialysis?

Use of ultrapure dialysate (bacteria < 0.1 CFU/mL and endotoxin < 0.03 EU/mL) is associated with a reduction in inflammation and morbidity in patients treated with conventional thrice-weekly dialysis. The improved outcomes obtained with more frequent dialysis schedules have reawakened interest in home hemodialysis. More frequent dialysis also appears to reduce inflammation, and whether combining more frequent dialysis with use of ultrapure dialysate will have an additive effect on inflammation and its consequences remains unclear. Routinely producing ultrapure dialysate in a home environment with a conventional hemodialysis machine poses technical challenges related to the design of the equipment and the intermittent nature of hemodialysis. Solutions to these problems include use of a system in which the water-treatment equipment is fully integrated with the dialysis machine, use of dry-powder cartridges or sterile prepackaged liquids for bicarbonate concentrate, and use of a bacteria-retentive and endotoxin-retentive filter for final purification of the dialysate immediately before it enters the dialyzer. Alternatively, ultrapure dialysate may be achieved with newer machines designed specifically for home hemodialysis that use a new batch of dialysate for each treatment. The volume of dialysate available with these machines, however, currently limits their use to short-daily dialysis.     

Impact of bleach cleaning on the performance of dialyzers with polysulfone membranes processed for reuse using peracetic Acid

Dialyzer performance may change with reuse depending on whether or not the dialyzer is cleaned with bleach. Bleach is usually used in conjunction with formaldehyde as the germicide. Because few data are available for dialyzers cleaned with bleach and disinfected with peracetic acid, we examined dialyzer performance in a cross-over study of dialyzers containing polysulfone membranes reprocessed using bleach and peracetic acid or peracetic acid alone. Each dialyzer was used for a total of 16 treatments, or until it failed standard criteria for continued use. Urea, beta2-microglobulin, and albumin removal were determined during the first, second, seventh, and 16th use of each dialyzer. Urea removal did not differ between the two reprocessing methods and did not change with reuse. Overall, beta2-microglobulin removal remained unchanged in dialyzers reprocessed with peracetic acid alone, but tended to increase after the seventh use in dialyzers reprocessed with bleach and peracetic acid. Approximately 60% of beta2-microglobulin removal resulted from trapping of beta2-microglobulin at the dialyzer membrane. Albumin loss into the dialysate was clinically insignificant throughout the study with both reprocessing methods. These data show that the clearance of both small and large molecules by dialyzers containing polysulfone membranes is well maintained by reprocessing with peracetic acid and that additional cleaning with bleach has limited impact on performance.     

Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens

AIMS: The increasing use of high-flux membranes for hemodialysis has raised concerns that patients dialyzed with these membranes may be at higher risk of being exposed to cytokine-inducing bacterial substances in the dialysate than patients dialyzed with low-flux membranes. We investigated the permeability of various high-flux membranes for both purified E. coli lipopolysaccharide (LPS) as well as for LPS derived from Stenotrophomonas (Sten.) maltophilia. MATERIALS AND METHODS: An in vitro dialysis circuit with saline in the blood compartment of 3 dialyzers containing different membranes (polysulfone, helixone and Diapes) was employed. The dialysate was challenged with increasing doses of sterile filtrates derived from Sten. maltophilia cultures or with purified LPS from E. coli. Samples from the blood compartment were tested for cytokine induction (IL-1beta, IL-6 and TNF) in mononuclear cells as well as for LPS by limulus amebocyte lysate test (LAL). RESULTS: IL-6 induction above sterile controls (< 0.02 ng/ml IL-6) was observed by samples from the blood side of DIAPES dialyzers (1.2 +/- 0.7 ng/ml IL-6) after challenging the dialysate with 4.1 +/- 3.6 U/ml E. coli LPS (9.9 +/- 4.5 ng/ml IL-6). In contrast, at the same challenge dose no significant IL-6 induction above sterile controls was observed by blood side samples of polysulfone (0.15 +/- 0.07 ng/ml) and helixone (0.09 +/- 0.05 ng/ml) dialyzers. Increasing the amount of E. coli LPS in the dialysate further augmented IL-6 induction by blood side samples of Diapes but not of polysulfone and helixone dialyzers. Similar results were obtained for IL-1beta and TNF. After challenging the dialysate with E. coli LPS as well as with cultures of Sten. maltophilia, significantly more LAL reactivity was observed in the blood compartment of Diapes compared to polysulfone and helixone. CONCLUSIONS: There are considerable differences between high-flux membranes regarding their permeability for cytokine-inducing substances from E. coli as well as for LPS derived from E. coli and Sten. maltophilia. Dialyzers that leak CIS under aqueous conditions in vivo should not be used unless the dialysate has passed through an ultrafilter.     

High-flux dialyzers, backfiltration, and dialysis fluid quality

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