Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors.

From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.     

Water permeability of high-flux dialyzer membranes after Renalin reprocessing

Dialysis with high-flux membranes is widely used, in part, because they are thought to increase the removal of middle molecules when compared with low-flux membranes. Dialyzer reprocessing; however, is thought to alter middle molecule clearance. Renalin, a mixture of germicidal agents, has widespread use in dialyzer reprocessing. We determined the effect of Renalin reprocessing on the water permeability of three different dialyzers of Fresenius (F80A and 200A) and Gambro (17R) manufacture using the dead-end filtration method. Two hundred and seventeen, predominantly used but some new, dialyzers were evaluated. Water permeability of the used, but not the new, dialyzers fell abruptly and dramatically with reprocessing. The permeability fell almost 70% in the F80A dialyzer after three reprocessing procedures with similar, but somewhat slower declines, seen in the other two dialyzers. We conclude that there is a decline in water permeability seen in Renalin reprocessed dialyzers. This factor and the associated change in solute clearance and ultrafiltration characteristics should be considered in assessing the effectiveness of dialyzer reprocessing.     

An Outbreak of Pyrogenic Reactions in Chronic Hemodialysis Patients Associated with Hemodialyzer Reuse

Abstract: In February 1992, 22 patients undergoing chronic hemodialysis at an outpatient dialysis center experienced pyrogenic reactions (PR). The PR rate was significantly greater (p < 0.001) during the epidemic (February 3–5) than the pre-epidemic period (November 1, 1992-February 1, 1992). All patients with PR used dialyz-ers that had been manually reprocessed either on February 1 or 3. These dialyzers contained up to 120.8 EU/ml of endotoxin in the blood compartment. The only dialyzer reprocessed before February 1 that was available for analysis was found to contain no detectable endotoxin, while dialyzers reprocessed during the epidemic period contained a median endotoxin concentration of 52.8 EU/ ml. The bioburden of water used to prepare dialysate was in excess of the Association for the Advancement of Medical Instrumentation (AAMI) standard for water, ≤200 colony forming units (CFU)/ml. Samples of treated water collected in the reuse area were within AAMI standards at the time of the investigation (February 11 and February 26), but before the investigation, water samples were assayed with a culture method that could not detect micro-bial concentrations below 10³ CFU/ml. In addition, the treated water feed line to the disinfectant container may never have been disinfected. However, no samples were collected from this line during the investigation. This outbreak emphasizes the need to use water that meets the AAMI bacteriologic and endotoxin standards of ≤200 CFU/ml and/or 5 EU/ml, respectively, for reprocessing hemodialyzers and to ensure that appropriate culture techniques are used for treated water and dialysate.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

Plate, Coil, and Hollow-Fiber Cuprammonium Cellulose Dialyzers: Discrepancy Between Incidence of Anaphylactic Reactions and Degree of Complement Activation

During the past 10 years, the incidence of severe anaphylactic reactions during dialysis [type A first-use syndrome (FUS)] at our center has been much lower when using cuprammonium cellulose plate (CC-P) dialyzers (0/37, 750 dialyses) or coil (CC-C) dialyzers (0/32, 500) than when using cuprammonium cellulose hollow-fiber (CC-F) dialyzers (8/21,022 dialyses, p less than 0.005 by Chi-square). To determine if the difference in type A FUS incidence between the three dialyzer types could be explained by differences in complement activation, we compared plasma concentrations of C3a des-arginine (des arg) in patients undergoing dialysis with these three varieties of dialyzers. Plasma C3a des arg values increased markedly in the dialyzer outflow blood with the three dialyzer configurations. The levels were similar with the dialyzer types when results were corrected for membrane surface area. Also, the degree of leukopenia was not markedly different with the three dialyzer types. Our findings suggest that complement activation per unit surface area is similar during dialysis with plate, coil, and hollow-fiber cuprammonium cellulose dialyzers. The lack of correlation between the degree of complement activation and the incidence of type A FUS suggests that membrane-induced complement activation is not of primary importance to type A dialyzer hypersensitivity reactions.     

Acute Anaphylactoid Reactions During Hemodialysis in France

A retrospective survey of anaphylactoid reactions during dialysis in France was conducted. In 52 of 112 hemodialysis units surveyed 111 patients who had suffered one or more anaphylactoid reactions during dialysis were identified. According to the Hamilton/Adkinson classification, in 31 patients reactions were minor, in 54 patients moderate, and in 26 patients severe. Four patients died of their reactions. A preponderance of reactions (75 and 11%) occurred with cuprammonium cellulose hollow-fiber and plate dialyzers, respectively. Severe dialyzer reactions were found to occur more frequently after the long (weekend) interdialytic interval. In an in vitro study, six brands of cuprammonium cellulose hollow-fiber dialyzers were rinsed with water and the eluates analyzed by size exclusion chromatography for contaminant particles. Substantial variation in the amount of extractable material was found between dialyzers of different brands, despite the fact that all dialyzers used membranes from the same manufacturer. Previous data by others has suggested that this extractable material is a derivative of cellulose. Results of our epidemiologic survey in France are similar to those previously reported in the United States and suggest an increased incidence of dialyzer reactions with ethylene oxide-sterilized cuprammonium cellulose dialyzers. The presence of cellulose-derived particles in the rinsing fluid of such dialyzers and the possible increased incidence of reactions after the long (weekend) interdialytic interval suggest that allergy to cellulose-derived particles eluted from cellulosic dialyzers may contribute to dialyzer hypersensitivity reactions.     

Evaluation of Three Dry-Sterilized Hollow Fiber Artificial Kidneys

We investigated three new dry sterilized hollow fiber artificial kidneys (HFAK) (Cordis Dow CDAK 1.3, Travenol CF 1200, Extracorporeal Tri-Ex 1). Dry sterilization makes these dialyzers more economical by shortening set-up time. Dry sterilization also eliminates iatrogenic administration of residual sterilant. Water of imbibition can significantly increase the blood compartment volume of the dialyzer during dialysis. Consequently, a corrected blood volume for each dialyzer was established; these corrected volumes varied from 13-36% greater than the volume determined before dialysate flow. With low dose heparinization of these dialyzers there was between an 18 and 45% decrease in the post dialysis volume, presumably due to fiber clotting during dialysis. This volume added to the residual blood loss measured by a colori-metric technique accounted for a possible blood loss ranging between 26.9 and 53.9 ml per dialysis for these three dialyzers. Our results suggest that a relationship between dialyzer clotting and decreased dialyzer efficiency may exist. These three capillary flow dialyzers had a much lower platelet drop (0-9% pre to post) when compared to 30-40% drop of flat plate dialyzers. These dialyzers were found to be safe and easy to use but the high fiber clotting warrants further investigation in chronic dialysis patients on high dose heparin.     

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.     

Dialyzer reuse--part II: advantages and disadvantages

Although single dialyzer use and reuse by chemical reprocessing are both associated with some complications, there is no definitive advantage to either in this respect. Some complications occur mainly at the first use of a dialyzer: a new cellophane or cuprophane membrane may activate the complement system, or a noxious agent may be introduced to the dialyzer during production or generated during storage. These agents may not be completely removed during the routine rinsing procedure. The reuse of dialyzers is associated with environmental contamination, allergic reactions, residual chemical infusion (rebound release), inadequate concentration of disinfectants, and pyrogen reactions. Bleach used during reprocessing causes a progressive increase in dialyzer permeability to larger molecules, including albumin. Reprocessing methods without the use of bleach are associated with progressive decreases in membrane permeability, particularly to larger molecules. Most comparative studies have not shown differences in mortality between centers reusing and those not reusing dialyzers, however, the largest cluster of dialysis-related deaths occurred with single-use dialyzers due to the presence of perfluorohydrocarbon introduced during the manufacturing process and not completely removed during preparation of the dialyzers before the dialysis procedure. The cost savings associated with reuse is substantial, especially with more expensive, high-flux synthetic membrane dialyzers. With reuse, some dialysis centers can afford to utilize more efficient dialyzers that are more expensive; consequently they provide a higher dose of dialysis and reduce mortality. Some studies have shown minimally higher morbidity with chemical reuse, depending on the method. Waste disposal is definitely decreased with the reuse of dialyzers, thus environmental impacts are lessened, particularly if reprocessing is done by heat disinfection. It is safe to predict that dialyzer reuse in dialysis centers will continue because it also saves money for the providers. Saving both time for the patient and money for the provider were the main motivations to design a new machine for daily home hemodialysis. The machine, developed in the 1990s, cleans and heat disinfects the dialyzer and lines in situ so they do not need to be changed for a month. In contrast, reuse of dialyzers in home hemodialysis patients treated with other hemodialysis machines is becoming less popular and is almost extinct.     

Effect of Reuse on Dialyzer Efficacy

The effect of reuse on dialyzer efficacy was examined by measuring blood compartment volume and dialyzer mass transfer coefficient (maximum dialyzer clearance) as a function of dialyzer use number. The 102 polysulfone dialyzers tested (F60 and HF80, Fresenius) were reprocessed on Renatron machines using peroxyacetic acid as the dual cleansing and sterilizing agent. Each dialyzer was used an average of 14.4 +/- 5.7SD times and was tested once (twice for 13/102 dialyzers) during a routine dialysis session at an arbitrary use number (7.6 +/- 5.3; range 1 to 24). The parameters tested were found to decrease only marginally with reuse, corresponding to a blood compartment volume loss of approximately 1% (R = 0.04) over a 5-week/15-use period and a decrease in dialyzer mass transfer coefficient of approximately 3% (R = 0.07 and 0.06) over the same period for urea and creatinine, respectively. It was concluded that the loss in dialyzer efficacy is negligible over the average use period of almost 5 weeks per dialyzer.     

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.     

Dialyzer performance over prolonged reuse

Studies were performed in patients on maintenance hemodialysis to evaluate the role of prolonged dialyzer reuse in the management of end-stage renal disease. For this purpose the patients were dialyzed without interruption with the same hollow fiber dialyzers (GambroR 120M) reprocessed with the Lixivitron IIR equipment. The data obtained from in vivo clearances in sixteen patients demonstrate that membrane permeability to small solutes (urea, creatinine, phosphate) is maintained up to thirty dialyzer uses. In vitro studies confirmed this observation and established that clearances of larger solutes (vitamin B12) are also maintained over similar extensive dialyzer reuse. Hematological and blood gas studies were performed serially during dialysis in five additional patients. Although circulating leucocyte and neutrophil counts, hemoglobin concentration as well as arterial pH and partial pressures of oxygen and carbon dioxide changed appropriately during dialysis, there was no observable difference from the first to the twentieth use of the same dialyzer. Thus, these results clearly demonstrate that prolonged dialyzer reuse in end-stage renal disease patients constitutes a stable form of renal replacement therapy provided adequate dialyzer reprocessing is applied.     

Ofloxacin clearance during hemodialysis: a comparison of polysulfone and cellulose acetate hemodialyzers

The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage renal disease during hemodialysis using two different dialyzers: a polysulfone membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T). All patients received 100 mg ofloxacin orally per day before dialysis. The hemodialysis clearance per square meter surface area was significantly different, with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively. The serum concentration was reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area and 45.5%+/-4.8% per square meter surface area. The half-life was 4.2+/-1.8 hours and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and 23.3+/-1.7 hours between the dialysis sessions, respectively. Comparing polysulfone and cellulose acetate dialyzers, the material of the membrane influences the half-life, the dialysis clearance, and the percentage of drug extracted during hemodialysis. We conclude that the type of dialyzer used has to be taken into account in dosage recommendations for antimicrobial therapy in hemodialysis patients.     

Outbreaks of infection and/or pyrogenic reactions in dialysis patients

These dialysis-related outbreaks demonstrate the ongoing potential for infection-related morbidity and mortality among dialysis patients. Many of these outbreaks could have been prevented by adequate water treatment, proper disinfection of water systems and dialysis machines, adherence to recommended reprocessing protocols in centers reusing dialyzers, and more stringent quality control monitoring. Finally, these outbreaks highlight the importance of active surveillance for adverse events among dialysis patients. The incidence of gram-negative bacteremia, pyrogenic reactions, and peritonitis should be monitored over time and any increase in incidence investigated.     

Residual Formaldehyde in Dialyzers: Quantity, Location, and the Effect of Different Methods of Rinsing

When formalin-sterilized dialyzers were rinsed by our standard technique (similar to that used in many other dialysis centres) undesirable concentrations of formaldehyde were found in the dialyzers at the start of dialysis. When the technique was modified by passing part of the saline through the blood compartment immediately before connection and discarding the saline left in the dialyzer at the time of connection, the concentration of formaldehyde infused into the patient fell below 2 μg/ml. However, the dialyzers still contained up to 13 mg of formaldehyde which leached slowly from the dialyzer during simulated dialysis. Some residual formaldehyde was found in several components of the dialyzer but the great majority was contained in the cellulose membrane.     

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.     

Cardiac biomarkers are influenced by dialysis characteristics

INTRODUCTION: The cardiac biomarkers cardiac Troponin T (cTNT) and NT-proBNP tend to be elevated in nearly all hemodialysis patients. The high percentage and magnitude of these increased molecules is associated with cardiovascular morbidity and mortality in hemodialysis patients. This study investigates the impact of the dialysis procedure itself on cardiac biomarkers. METHODS: Standard chronic hemodialysis lasting 4-5 hs 3 times weekly and using polysulfone dialyzers (high-flux and low-flux) was performed. Blood flow rates varied between 250-350 ml/min. The cTNT levels of 49 chronic hemodialysis patients were measured twice (interval of 6 weeks) before and after a hemodialysis session by a third-generation assay (Elecsys Analyzer, Roche Diagnostics, Mannheim, Germany). NT-proBNP levels were measured with polyclonal antibodies capable of recognizing the N-terminal fragment of BNP. In a follow-up period of 42 months, cardiovascular events and death were assessed. RESULTS: The median concentration of cTNT prior to hemodialysis was 0.024 ng/ml (< 0.001-0.703). All dialysis patients presented high plasma levels of NT-proBNP (median 4,885 pg/ml). Oligoanuric patients had significantly higher cTNT and NT-proBNP levels prior to dialysis compared to patients with normal diuresis (p < 0.0001). cTNT and NT-proBNP levels increased significantly during the hemodialysis sessions in which a low-flux dialyzer was used (p < 0.0001) but remained unchanged when a high-flux dialyzer was utilized. Neither the predialytic nor the interdialytic changes in cTNT and NT-proBNP levels were influenced by blood flow. NT-proBNP levels increased markedly during hemodialysis sessions (p < 0.005) utilizing the low-flux dialyzer. Patients with a non-native fistula had significantly higher predialysis cTNT and NT-proBNP levels (p < 0.05). Patients with cardiovascular events had a significantly higher cTNT and NT-proBNP at the beginning of the study. CONCLUSION: Asymptomatic chronic hemodialysis patients have significantly higher levels of the cardiac biomarkers cTNT and NT-proBNP relative to the general population. The levels are associated with the time of measurement (before and after a hemodialysis session). Dialysis modalities like high-flux dialyzers influence cTNT and NT-proBNP levels and should be taken into account, particularly in patients with acute onset of cardiac ischemia. The elevation of cTNT and NT-proBNP levels after hemodialysis using a low-flux dialyzer are partly due to hemoconcentration. The significant association of cTNT and NT-proBNP with non-native fistulas (catheter or graft) may be due to the chronic inflammation commonly caused by these devices. Both cardiac biomarkers are of prognostic value determining cardiovascular events and death.     

Beta 2-microglobulin kinetics in maintenance hemodialysis: a comparison of conventional and high-flux dialyzers and the effects of dialyzer reuse

beta 2-Microglobulin (beta 2M) forms synovial and bony amyloid deposits in long-term hemodialysis patients. To define the kinetics of beta 2M during hemodialysis and the effects of dialyzer reprocessing, we measured serum beta 2M, plasma C3a, and neutrophil counts immediately predialysis; 15, 90, and 180 minutes after beginning dialysis; and 15 minutes postdialysis in ten chronic hemodialysis patients. The studies were performed during first and third uses of cuprammonium rayon and polysulfone dialyzers processed by rinsing with water, then bleach, in an automated system (Seratronics DRS 4) and then packed in 1.5% formaldehyde. Mean serum beta 2M (corrected for ultrafiltration) decreased by 16.6% +/- 18.1% with new cuprammonium dialyzers and 57.1% +/- 12.8% with new polysulfone dialyzers. Dialyzer reprocessing had no significant effect on this decline. Predialysis serum beta 2M decreased by 30.4% +/- 15.5% 1 month after switching from cuprammonium to polysulfone dialyzers; these levels remained stable after 3 months of dialysis with polysulfone. Complement activation and neutropenia during dialysis were significantly more marked with cuprammonium, but were not affected by reprocessing of either dialyzer. In vitro adsorption of 124I-beta 2M to polysulfone fibers was greater than to cuprammonium; adsorption was not influenced by dialyzer reprocessing.     

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)