Ethylene Oxide Sensitivity in Hemodialysis Patients

Sera from 138 patients who had experienced hypersensitivity-type reactions while on hemodialysis (reactors) were examined retrospectively by the radioallergosorbent test (RAST) for specific IgE antibody to ethylene oxide (ETO). Seventy-eight hemodialysis patients without a history of reaction were also evaluated as controls. Elevated serum RAST values (greater than 2.0) were more common in reactors (63%) than in controls (11%, p less than 0.001). In a second study, RAST assays were performed using human serum albumin conjugated to ETO (HSA-ETO) as antigen and also using a concentrate of fluid used to rinse ETO-sterilized dialyzers ("dialyzer extract") as antigen. The RAST ratios obtained with HSA-ETO were similar to those obtained using the dialyzer extract (rank order correlation coefficient = 0.829, p less than 0.001). In a third study, RAST inhibition was demonstrated both by HSA-ETO and dialyzer extract. Our results, extending previously published reports, suggest that hypersensitivity to ETO might play an important role in hemodialysis-associated hypersensitivity-type reactions.     

Ethylene Oxide in Dialyzer Rinsing Fluid: Effect of Rinsing Technique, Dialyzer Storage Time, and Potting Compound

Ethylene oxide (ETO) is recognized as one of the main causes of dialyzer-associated hypersensitivity reactions. We studied the amount of ETO in the rinsing fluid of ETO-sterilized hollow-fiber dialyzers as a function of rinsing technique, dialyzer storage time, and the amount of potting compound (known to be an ETO reservoir) in the dialyzer. The results suggested that the initial 500 ml of rinsing fluid removes much of the residual ETO in the dialyzer. Ethylene oxide extraction was enhanced substantially by rinsing at 37 degrees C versus 5 degrees C. However, considerable amounts of ETO remained in the dialyzer after an initial 500 ml rinse, some of which could be removed by rinsing with an additional 1,500 ml. High concentrations of ETO were measured in fluid that had been recirculated through the dialyzer for 10 min or longer and in fluid that had been allowed to remain in the dialyzer for 10 min under zero-flow conditions. The amount of ETO in the rinsing fluid decreased markedly as the dialyzer storage time was increased from 4 to 8 weeks and in dialyzers in which a portion of the potting compound had been replaced with a polycarbonate ring. Our results suggest that the dose of ETO administered to the patient at the outset of dialysis can be minimized by rinsing the dialyzer with 2 L of fluid at 37 degrees C and by avoiding administration of rinsing fluid that has been allowed to remain in contact with the dialyzer for more than several minutes. Use of a long storage interval and use of dialyzers containing reduced amounts of potting material will also reduce the ETO load.     

IgE Against Ethylene Oxide-Altered Human Serum Albumin (ETO-HSA) as an Etiologic Agent in Allergic Reactions of Hemodialysis Patients

Ethylene oxide (ETO) is used to sterilize hemodialyzers and other medical equipment. In an attempt to confirm a link between ETO and hypersensitivity reactions during hemodialysis (HD) we quantitated IgE and total antibody directed against ETO-altered human serum albumin (ETO-HSA) in the sera of 65 hemodialysis patients. In 24 patients who had experienced anaphylaxis during HD, the levels of IgE and total antibody against ETO-HSA were significantly higher than the corresponding levels in 41 patients who had not. Our data demonstrate an association between the presence of IgE and total antibody against ETO-HSA and immediate anaphylactic reactions to HD. In further studies we characterized the ETO-HSA antigen by immunoelectrophoresis, gel filtration chromatography, and cross-inhibition immunoassay. Our results suggested that ETO gas can alter HSA and induce new antigenic determinants on the molecule. Recently, we encountered a peritoneal dialysis patient with rash and eosinophilia. Suspecting ETO allergy, we measured serum IgE and total antibody to ETO-HSA and found both to be present. The data suggest that, in addition to the familiar HD reactions, ETO sensitization might cause other allergic diseases as well.     

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.     

Antibody Responses to Hemodialysis-Related Antigens in Chronic Hemodialysis Patients

Allergic-type reactions during hemodialysis are sometimes due to sensitization to ethylene oxide. To examine the possibility that additional antigens might be a basis for unexplained reactions, antibodies to formaldehyde and phthalate-related antigens and to dialyzer extracts were measured. Unselected sera from 113 chronic hemodialysis patients (CHP) and 200 control subjects were tested for IgG antibodies to formaldehyde-treated human serum albumin (HSA). The IgG antibody activity was confirmed in sera of five CHP who had used formaldehyde-treated dialyzers. These antibodies also reacted with formaldehyde-treated red blood cells. Sera from 71 CHP and 80 controls were tested for IgE antibodies to diethylphthalate-treated HSA; antibody was detected in two CHP sera. With extracts from hollow-fiber dialyzers, IgG antibody was detected in approximately 1/3 and IgM antibodies in approximately 1/2 of CHP sera. This antibody was found in comparable numbers of control sera. It was concluded that these additional substances are immunogenic and could be involved in allergic-type reactions.     

Anaphylactic Shock at the Beginning of Hemodialysis

In patients who receive hemodialysis, most hypersensitivity reactions to components of the dialysis circuit are due to ethylene oxide or complement activating bio‐incompatible membranes. We present a case of a 59 year‐old female, with a 4‐year history of uneventful hemodialysis using a cellulose based dialyzer membrane at her outpatient dialysis center, who developed repeated anaphylactic reactions associated with markers of an IgE mediated hypersensitivity reaction when a polysulfone based dialyzer membrane was used while she was hospitalized. Only when the patient's dialyzer was changed back to her usual cellulose based membrane, did these reactions cease. On the basis of her clinical course and laboratory findings, we concluded that the patient's symptoms were due to exposure to polysulfone. This case reminds us that “biocompatible” membranes are not free from dialyzer reactions, and can be especially severe if the mechanism is an IgE mediated anaphylactic hypersensitivity reaction.     

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.     

Relationship between dialyzer reuse and the presence of anti-N-like antibodies in chronic hemodialysis patients.

One hundred eleven chronic hemodialysis patients from five dialysis units were tested for the presence of antibodies reactive with red blood cell N substance; 77 patients were available for follow-up study after 18 to 24 months. Initially, 18 patients (16%) had serum anti-N-like antibodies. Thirteen of these patients were in a home dialysis program and were reusing hollow fiber dialyzers. The other five had practiced hollow fiber dialyzer reuse in the past. None of 37 patients using coil dialyzers had anti-N-like antibody. On follow-up testing, anti-N-like antibody persisted in all patients restudied except for one who had a successful renal transplant. Anti-N-like antibodies developed in four additional patients: three were reusing hollow fiber dialyzers at the time, but one had not reused dialyzers for 24 months. Statistical analyses indicated that dialyzer reuse, hollow fiber dialyzers, and home dialysis were significantly related to the presence of anti-N-like antibodies. We interpret the clinical and statistical data to indicate that dialyzer reuse is the major clinical factor in the development of anti-N-like antibody. The likely mechanism involves the prolonged exposure of red cells trapped in the dialyzer to formaldehyde used in preparing dialyzers for reuse. No adverse clinical effects of anti-N-like antibodies were evident in our patients, but hemolysis and acute transplant failure have been reported by others.     

Role of Dialyzer Contaminants in the Allergic Epiphenomena of Hemodialysis

Abstract: Cuprophan hollow-fiber dialyzers contain contaminants including 1,2,3-propanetriol, carbohydrates, Limulus amebocyte lysate-reactive material, and particulates. In a clinical study, the role of these substances in the allergic-type response seen in some hemodialysis patients was examined. Patients were dialyzed three times per week for 6-week intervals with each of four dialyzer preparations designed to vary the burden of contaminants presented to the patient. Predialysis eosinophil counts and serum immunoglobulin (Ig) E levels were obtained weekly. White cell and platelet counts and plasma C3a and C5a levels were measured during dialysis for each dialyzer preparation. Dialyzer preparation had no effect on predialysis eosinophil counts or IgE levels. All patients demonstrated transient leukopenia and complement activation during dialysis, the magnitudes of which were unaffected by the type of dialyzer preparation. At the levels found in the dialyzers studied, it was questioned whether water-soluble extractables or particulates play any role in the allergic epiphenomena of hemodialysis.     

Ethylene Oxide (ETO) as a Major Cause of Anaphylactoid Reactions in Dialysis (A review)

Ethylene oxide (ETO), an alkylating compound of high chemical reactivity, is widely used for gas sterilization, but recently serious ETO side reactions have been recognized. With chronic ETO exposure, increased spontaneous abortion, sister chromatid exchange, and leukemia are observed. After medical use of ETO outside nephrology, contact dermatitis, cardiopulmonary shock (during cardiopulmonary surgery), allergic local reactions to ETO sterilized lenses, and anaphylactoid reactions to ETO sterilized catheters have been described. In numerous dialysis patients widespread hypersensitivity to ETO has been documented by skin prick test and ETO radioallergosorbent test (RAST). Furthermore an anaphylactoid "first-use reaction" was described in dialyzed patients, most of whom were using hollow-fiber dialyzers. After long discussions whether complement activation versus hypersensitivity is the cause of such acute anaphylactoid reactions, more recent studies using either ETO RAST or basophil degranulation tests implicate ETO hypersensitivity as their major cause. The high prevalence of sensitization to ETO and the frequency, unpredictability, and potential danger of anaphylactoid reactions to ETO lead to the conclusion that ETO sterilization of dialyzers should be discontinued, since alternative modalities of sterilization are currently available.     

Effect of gamma radiation versus ethylene oxide sterilization of dialyzers and blood lines on plasma levels of granulocyte elastase in hemodialyzed patients

The effect of gamma versus ethylene oxide sterilization of different dialyzers (polyacrylonitrile, cuprophan) and blood lines on plasma levels of granulocyte elastase and of lysozyme during hemodialysis was investigated in 17 chronically uremic patients. Plasma levels of granulocyte elastase increased during hemodialysis but significantly less in the presence of polyacrylonitrile compared with cuprophan membranes. In contrast, enhanced lysozyme plasma levels decreased during dialysis using the polyacrylonitrile dialyzer to values of healthy controls and remained unchanged using the cuprophan dialyzer. Both effects were not influenced by the way of sterilization. We conclude that granulocyte activation during hemodialysis occurs independently of the sterilization procedure of dialyzers and blood lines in patients showing no clinical signs of hypersensitivity.     

Systemic Levels of Tumor Necrosis Factor Alpha During Hemodialysis with Cellulosic Membranes: No Effect of the Sterilization Procedure

Extractable constituents of dialyzer membranes (e.g., monomers and beta-glucans) may induce the production of cytokines in vitro. We therefore studied circulating tumor necrosis factor alpha (TNF alpha) levels in 23 stable hemodialysis patients during treatment with dry Cuprophan membranes (ETO-sterilized n = 10, steam-sterilized n = 13) longitudinally over a period of 4 weeks. After 4 weeks, those 5 patients of each group showing the highest TNF alpha levels were switched to steam-sterilized, wet Cuprophan membranes. No significant increase in plasma TNF alpha was observed during hemodialysis with either ETO- or steam-sterilized dry Cuprophan membranes. A substantial TNF alpha increase (> or = 100% compared to pre-HD values), however, was observed during 14 of 84 treatment sessions. In 5 selected patients with ETO-sterilized, dry Cuprophan dialyzers, TNF alpha rose from (mean +/- SEM) 17.2 +/- 3.0 (pre-HD) to 20.9 +/- 6.2 (120 min) and 21.9 +/- 4.5 pg/ml (240 min). Corresponding levels in patients with steam-sterilized, dry Cuprophan were 16.2 +/- 5.4 (pre-HD), 21.9 +/- 6.8 (120 min), and 16.0 +/- 3.7 pg/ml (240 min), respectively. There was no difference between ETO- and steam-sterilized dialyzers. No significant reduction in mean TNF alpha plasma levels or in frequency of elevated peak levels was achieved when these patients were switched to wet Cuprophan dialyzers for another 4 weeks. It is suggested that an induction of elevated TNF alpha levels during hemodialysis is possible but is not observed regularly during treatment with Cuprophan membranes.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Survey on Hypersensitivity Reactions in Hemodialysis

This survey was conducted from 1982 through 1984 by a cooperative effort among the Health Industries Manufacturers Association, seven dialyzer manufacturers, and the Food and Drug Administration. This article presents an analysis of the 1982-83 survey data and a summary of the 1984 data. Most of the reactions reported (99%) were associated with hollow-fiber dialyzers. About 50% of these reactions were experienced by patients using a dialyzer model for the first time, and greater than 98% of the reactions were related to new (unused) dialyzers. On average, there were 180 reactions reported per year, with greater than 90% being considered severe, including death, by the reporting center. A plot of the number of reactions versus time from 1982 through 1984 shows periods of 12-15 months in which the reaction rate remained practically constant. During these periods, the rate of reported reactions alternated from 60 to 150% of the average. Analysis of the survey data showed a strong correlation of the number of reactions with the race and age of the patients. Blacks and other minorities experience nearly three times as many reactions as white patients. Also, patients under 29 years of age seem to have nearly twice as many reactions as patients in the 30- to 49-year-old range, whereas patients over 50 years old have nearly half the number of reactions of the 30- to 49-year-old range. The average reactivity of the U.S. hemodialysis patient population was calculated to be 3.3 reactions per year per 1,000 patients exposed to hollow-fiber dialyzers and 0.3 reaction per year per 1,000 patients exposed to flat-plate dialyzers.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Fluid phase generation of terminal complement complex as a novel index of bioincompatibility

Blood membrane interactions in hemodialysis have been shown to trigger complement (C) activation. As indicators of C-activation the anaphylatoxins (C3a and C5a) are problematical because of methodological difficulties and their kinetic properties. We developed a sensitive and specific micro-ELISA using a monoclonal antibody against neoantigens on the terminal complement complex (TCC); highly purified human TCC served as standard. Concentrations of TCC were measured in single-path perfusion systems (in vitro) and in the blood lines (arterial inlet; venous outlet) of patients on hemodialysis using steam-sterilized or ETO-sterilized dialyzers with the following membranes: cuprophan (CU), hemophan (HE) and polysulfone F6 (PS), respectively. All dialyzers with identical geometry were run under identical conditions. All membranes tested caused continuously ongoing net generation of TCC. In vitro, contact of serum with CU minidialyzers resulted in fivefold higher net release of TCC compared with HE and PS. In vivo TCC concentration-time profiles differed significantly between membranes in the rank order CU much much greater than HE greater than PS (mean basal concentration 58 x 10(-11) M; peak increase over baseline with CU 40-fold, HE fourfold, PS threefold). In addition, more TCC was generated from the same dialyzers with ETO than steam sterilization. TCC differed from C3a and C5a in the following respects: (i) lower detection limit (4 x 10(-11) vs. less than 5 x 10(-9) M for both C-anaphylatoxins); (ii) higher relative increment (inlet) during CU dialysis (25-fold vs. eightfold and twofold, respectively); (iii) C-anaphylatoxins yielded the same ranking (CU much greater than HE greater than PS), but TCC concentrations were not a linear function of C3a or C5a concentrations, respectively. Kinetic analysis (Bateman function) showed significant differences of invasion constants between membranes, that is, CU 0.088 min-1, HE 0.09, PS 0.168. The net amount of TCC released from the dialyzer was calculated under certain assumptions. It was 75.5 mg/4 hr for CU, 7.3 for HE and 5.0 for PS. The elimination constant was also dependent on the type of membrane. Using flow cytofluorometry and immunohistochemical methods (APAAP), TCC was demonstrated on membranes of granulocytes obtained during dialysis; this is compatible with potential in vivo cell activation. Generation of PGE2 and TNF alpha by adherent monocytes induced by cuprophan was C8 dependent: levels were significantly increased by addition of C8 to C8 deficient human serum concomitantly with generation of TCC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunologic Studies of Hollow-Fiber Dialyzer Extracts

Abstract: Testing failed to detect free isocyanates in dialyzer rinses or significant levels of immunoglobulin E antibodies to isocyanate-protein conjugates in the serum of individuals reacting during hemodialysis with dialyzers containing Cuprophan membranes. Extended immunization of rabbits with Limulus lysate-reactive material from dialyzer rinses demonstrated antigenic activity of the rinse that appears to originate from cotton linters used in hollow-fiber membranes. The possibility that an immunologic response to these antigens may be a mechanism in adverse reactions to hemodialysis is discussed.     

Anaphylactoid reactions in hemodialysis patients treated with the AN69 dialyzer.

During an 11 week period (May to July, 1990), we observed six anaphylactoid reactions (AR) in six different hemodialysis patients occurring at the onset of treatment with a new AN69 hollow-fiber dialyzer. Four patients required cardiopulmonary resuscitation and one of these expired. Four patients were also receiving an angiotensin converting enzyme (ACE) inhibitor while the other two were not on medication known to affect the renin-angiotensin system. Only patients treated with AN69 dialyzers were affected. A review of the literature indicated that out of 1087 patients reported, 72 patients were on the combination of an AN69 dialyzer and ACE inhibitor therapy and 41 (57%) demonstrated AR. Only two patients (0.4%; both from our series) treated with an AN69 dialyzer without ACE inhibitor therapy developed AR. AR did not occur in patients treated with a variety of other dialyzers during this 11 week period, with or without ACE inhibition. Possible causes for AR are discussed and include: (1.) blood-AN69 membrane interaction leading to the production of bradykinin and other vasodilators, the breakdown of which may be delayed by the presence of ACE inhibitors; (2.) hypersensitivity to ethylene oxide; (3.) passage of bacterial products from dialysate to blood; (4.) changes in membrane manufacturing specifications. Recommendations are proposed for the prevention and treatment of AR.     

Removal of acyclovir during continuous veno-venous hemodialysis and hemodiafiltration with high-efficiency membranes

We present a critically ill patient with severe renal failure and anuria who underwent hemodialysis (HD), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF) at different occasions, with 2 commonly used high-efficiency dialyzers (F-8 and CA-210), while receiving i.v. acyclovir. We estimate that during 24 hours of CVVHD with F-8 dialyzer approximately 18% and during 24 hours of CVVHDF with CA-210 dialyzer approximately 65% of the daily administered acyclovir is removed. This is comparable to the amount removed during 4 6 hours of HD, as reported previously. The percentage acyclovir extraction was 84% and 60% during CVVHD and CVVHDF with F-8 and CA-210 dialyzers, respectively. Acyclovir clearance during CVVHD was 14 ml/min and during CVVHDF was 17 ml/min, with F-8 and CA-210 dialyzers, respectively. Acyclovir half-life was 22.5 and 25.5 hours in 2 occasions off any type of renal replacement therapy, and it was 19.5 hours during CVVHDF with CA-210 dialyzer.     

The significance of preformed aprotinin-specific antibodies in cardiosurgical patients

Acute hypersensitivity reactions are serious complications of reexposure to aprotinin. Previous contact via infusions or fibrin tissue adhesives can induce specific antibodies. In this study, we aimed to elucidate the preoperative prevalence of aprotinin-specific antibodies in patients scheduled for cardiac operations. Sera of 520 consecutive cardiosurgical patients were collected preoperatively and screened retrospectively for aprotinin-specific IgG using a standard enzyme-linked immunosorbent assay (ELISA). Positive sera were analyzed also for aprotinin-specific IgA (ELISA) and IgE (fluorescence enzyme immunoassay). The histories of all patients were reviewed with focus on aprotinin preexposure. Of 520 patients, 22 (4%) had specific IgG. Only three of these had a documented aprotinin preexposure. Of 448 patients exposed to aprotinin intraoperatively, 15 had preformed specific antibodies. The only patient presenting with severe anaphylaxis was positive for both IgG and IgE, and had a recent IV preexposure in cardiovascular surgery. The presence of aprotinin-specific IgG alone seems not to induce adverse reactions on exposure. Exposure history alone is not sensitive enough to identify patients with aprotinin-specific antibodies. IMPLICATIONS: Anaphylaxis on IV reexposure to aprotinin is a medical emergency. The clinical significance of preformed aprotinin-specific IgG remains questionable, whereas preformed IgE was present in the only patient who suffered from severe anaphylaxis on reexposure to aprotinin. Preformed antibodies are not reliably predicted by exposure history.     

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.