Anaphylatoxin formation during hemodialysis: comparison of new and re-used dialyzers

Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of these same patients. By contrast, hemodialysis with re-used dialyzers, that is dialyzers exposed to blood prior to formalin sterilization, produced only a 20 to 30% decline in peripheral blood leukocyte counts. Correspondingly, C3a antigen formation within re-used dialyzers was only 20% of that observed in new dialyzers. Re-used dialyzers also differed significantly from either new or formalin-fixed new dialyzers in that C3b antigen could be readily detected within them even after extensive washing. These observations suggest that C3b deposition on the cellulosic membrane surface during first use markedly diminishes the complement activating potential of cuprophan dialyzers when they are subsequently re-used.     

Complement Activation During Hemodialysis: Clinical Observations, Proposed Mechanisms, and Theoretical Implications

Abstract: Human C3a radioimmunoassay techniques were employed to define both the temporal profile and the amount of complement activation taking place in the extracorporeal circuit during maintenance hemodialysis. Prospective studies demonstrated that C3a formation, like hemodialysis-associated leukopenia, was a transient phenomenon that occurred predominantly during the first 30 min of dialysis. Quantitative comparisons revealed that new Cuprophan hemodialyzers displayed somewhat greater complement-activating potential than cellulose acetate dialyzers. By contrast to new Cuprophan membranes, both reused Cuprophan and polyacrylonitrile dialyzers exhibited only a modest ability to activate human complement. These findings are compatible with the known mechanisms of complement activation and suggest that certain chemical and biochemical methods might be exploited to enhance the biocompatibility of cellulose dialysis membranes.     

Plasma levels of main granulocyte components in patients dialyzed with polycarbonate and cuprophan membranes

Plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) were investigated in regular hemodialysis patients dialyzed with hollow-fiber dialyzers made from polycarbonate (FD 100) or cuprophan (GFS 120 H). Plasma levels of all these main granulocyte components increased significantly during hemodialysis. E-alpha 1PI levels were significantly higher in patients dialyzed with the polycarbonate compared with the cuprophan membrane, whereas the increases of myeloperoxidase and lactoferrin were not different for the two dialyzers. On the other hand, plasma C3a levels were higher in patients dialyzed with the cuprophan compared with the polycarbonate dialyzer. Therefore, granulocyte activation during hemodialysis does not necessarily need complement activation.     

Compartmental distribution of complement activation products in artificial kidneys

The compartmental distribution of the human anaphylatoxins C3a and C5a has been defined during simulated hemodialysis performed with various types of hemodialyzers. New cuprophan hollow fiber dialyzers were found to activate human complement very readily in vitro, while re-used cuprophan dialyzers displayed only modest complement activating potential. The C3a and C5a antigens, formed as a result of complement activation in these dialyzers, accumulated predominantly in the blood path and were not adsorbed extensively on the membrane surface or transported into the dialysate compartment. Cellulose acetate membranes also produced complement activation in vitro, but to a lesser degree than new cuprophan hollow fibers. However, these membranes exhibited a significant capacity to bind the anaphylatoxins to their surface. Polyacrylonitrile membranes appeared to be unique in that they not only failed to activate complement significantly, but they rapidly adsorbed large quantities of C3a and C5a. These findings demonstrate that hemodialysis membranes may differ with regard to their complement activating potential as well as their ability to remove circulating anaphylatoxins from the blood path. Clinical measurements of anaphylatoxin production during hemodialysis reflect these dynamic events.     

Effect of dialyzer geometry on granulocyte and complement activation

During hemodialysis with cuprophan membranes, the complement system as well as leukocytes become activated. In order to clarify the role of dialyzer geometry, the effect of hollow-fiber versus flat-sheet dialyzers and of different surface areas on C3a generation and leukocyte degranulation was investigated. Plasma levels of leukocyte elastase in complex with alpha 1-proteinase inhibitor were significantly increased after 1 h (+55%) and 3 h (+62%) of hemodialysis with flat-sheet dialyzers as compared to hollow-fiber devices. In addition, plasma levels of lactoferrin, released from the specific granules of leukocytes during activation, were significantly higher (+42%) 3 h after the onset of dialysis treatment with flat-sheet than with hollow-fiber dialyzers. With respect to surface area, larger dialyzers tended to cause more release of leukocyte elastase as compared to dialyzers with smaller surface areas, irrespectively of the configuration of the dialyzer used. On the other hand, activation of the complement system, as measured by the generation of C3a-desarg, did not differ with both types of configurations. The same held true for leukopenia, which was almost identical for hollow-fiber and flat-sheet dialyzers. From these findings two lines of evidence emerge: First, not only the type of membrane material used in a dialyzer may influence its biocompatibility, but the geometry of the extracorporeal device also determines the degree of compatibility. Hence, the extent of leukocyte activation correlated with both configuration of the dialyzer and surface area of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Plasma levels of complement fragments during hemodialysis in patients with chronic renal failure

The kinetics of hemodialysis-induced leukopenia and generation of complement fragments including C3a, C5a, C4d, iC3b and Bb were investigated in 14 patients during hemodialysis using cellulose acetate (CA), cuprophan (Cu) and ethylenevinyl alcohol (EVA) membranes. A marked leukopenia in the first 15 minutes was observed in CA and Cu. Plasma C3a levels were higher in CA than in Cu and EVA. Plasma C5a levels were higher in CA and Cu than in EVA. There was a negative correlation between the white blood cell counts and plasma C5a levels at 15 minutes (gamma = -0.85, p less than 0.001). Plasma C4d levels showed no increase in all membranes. Plasma iC3b levels were higher significantly in Cu than in CA and EVA. Plasma Bb levels in the first 15 minutes increased significantly in all membranes, and furthermore continued to increase till the end of hemodialysis in CA and Cu. This study revealed that all the membranes tested activated the complement via the alternative pathway to produce Bb, iC3b, C3a and C5a. C5a was thought to take an important role in transient leukopenia. Furthermore, Bb was accumulated during hemodialysis in CA and Cu, and its biological effects on patients undergoing hemodialysis should be studied.     

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.     

Adherence of neutrophils to hemodialysis membranes: role of complement receptors.

Complement activation occurs during hemodialysis using cellulosic dialysis membranes with the consequent deposition of C3 activation and degradation products on the membrane surface. To determine if these complement fragments are functionally active, we examined their capacity to mediate leukocyte adherence to cuprophan membranes. Immunoblotting of proteins eluted from plasma-treated cuprophan membranes confirmed the presence of both C3b and iC3b. Incubation of cuprophan membranes with heparinized whole blood resulted in adherence of leukocytes but not erythrocytes. Neutrophils were the primary cell type bound, with monocytes comprising less than 5% of the adherent cells. Studies using indium-labeled neutrophils demonstrated that the binding was plasma dependent and increased with time up to two hours. Neutrophil binding was inhibited by preincubation of the plasma-treated cuprophan membrane with anti-C3 or preincubation of neutrophils with an antibody directed against the alpha chain of complement receptor type 3 (CR3). These observations indicate that iC3b deposited on cuprophan membrane surface as a result of complement activation mediates neutrophil adherence via interaction with CR3. They also support the hypothesis that, in addition to the anaphylatoxins released into the fluid phase, complement activation products that remained membrane bound during hemodialysis also stimulate pathophysiological responses.     

In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions

BACKGROUND: The aim of this study was to develop a model for hemodialysis (HD) in small animals using conventional dialysis equipment that would allow the intravital microscopic observation of leukocyte-endothelial interactions in vivo. METHODS: Cuprophan dialyzers were adapted to obtain a similar ratio of membrane area to blood volume as in clinical HD. A silicone ring was inserted into the dialyzer's inlet to limit the number of blood-perfused capillaries. Rabbits were dialyzed for one hour without a dialysate flow. RESULTS: Extracorporeal circulation with the cuprophan dialyzer resulted in a transient leukopenia and complement activation. At the nadir of leukopenia, leukocytes that rolled along the venular wall were scarcely observed, whereas rolling was abundant (54 +/- 9 per min) prior to extracorporeal circulation. The adhesion of leukocytes to the vascular endothelium was not induced. After 60 minutes, rolling of leukocytes was still reduced by 73 +/- 5.5%, despite the full recovery of circulating leukocyte counts. Extracorporeal circulation without a dialyzer also tended to reduce leukocyte rolling, although systemic leukocyte counts were not affected. CONCLUSIONS: The use of adapted conventional cuprophan hemodialyzers in rabbits yielded a transient leukopenia similar to that in clinical HD. Using intravital microscopy, we demonstrated impairment of leukocyte-endothelial interactions. In addition, our data indicate that tissues, in which leukocytes can roll and adhere, are not automatically sites of leukocyte sequestration during HD-induced leukopenia.     

Adsorption of unactivated complement proteins by hemodialysis membranes

Hemodialysis using polyacrylonitrile (PAN) membranes has been reported to be associated with depletion of complement in the plasma, yet the increase in plasma C3a antigen concentrations and the degree of leukopenia are modest. These observations suggest that PAN membranes may have a large propensity to adsorb native complement proteins; as a consequence, complement depletion can occur without activation. In the present study, we observed that incubation of human serum in the presence of PAN membrane resulted in a 50% loss of serum hemolytic activity of C3. When radiolabeled purified components were offered, PAN membranes were found to adsorb C3 and C5 in a dose-dependent manner. Adsorption of these proteins by PAN was more than 20 times greater than adsorption by cuprophan, cellulose acetate or Hemophan (Akzo, formerly Enka, Wuppertal, FRG) at all concentrations examined. These results suggest that depletion of complement when serum is exposed to hemodialysis membranes may result from adsorption of complement components onto the membrane surfaces and does not necessarily indicate complement activation.     

Dialysis-induced hypoxemia: membrane dependent and membrane independent causes

Hypoxemia during hemodialysis may result from several differing processes. We initially studied patients undergoing standard acetate hemodialysis. At 15 minutes of dialysis, leukopenia (primarily neutropenia), a decline of platelet count, and hypoxemia occurred, but without a significant change in mean minute ventilation. Complement activation (V/A ratios of C5a greater than 1.0) persisted throughout dialysis. Leukocyte count returned to baseline by one hour. To separate the effects of solute and/or gas fluxes from those of blood-membrane interaction we studied changes in Po2, WBC, C5a, TxB2, and PGI2 during a period of blood membrane interaction without dialysis, and during subsequent acetate dialysis. Patients were studied with both polyacrylonitrile (PAN) and cuprophan membranes containing different priming solutions during membrane contact alone. Despite leukopenia and complement activation, hypoxemia failed to occur during membrane contact alone. At 15 minutes of subsequent acetate dialysis, significant hypoxemia occurred with both membranes. However, the degree of hypoxemia was twice as great with a cuprophan membrane primed with acetate (18.6 +/- 3.3 mm Hg) compared with air or bicarbonate (9.1 +/- 1.4 and 7.0 +/- 2.0 mm Hg, respectively), or compared with PAN (8 +/- 2.8 mm Hg). Changes in thromboxane B2, PGI2, and C5a did not correlate with changes in Po2. We conclude that there are two major components to dialysis related hypoxemia. One is membrane independent, and may relate to the metabolic effects of acetate or to dialyzer CO2 loss. The remaining portion is membrane dependent, occurring with cuprophan, but not with PAN, and is conditioned by an acetate dependent interaction between blood and membrane.     

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)     

Establishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients: a randomized prospective study

The present prospective study was conducted in order to establish the relationship between complement activation and stimulation of phagocyte oxidative metabolism observed in long-term hemodialysis (HD) patients during the early phase of dialysis with cellulosic membranes. Two groups of 10 randomized (HD) patients treated with cellulosic (Cuprophan, CUP) or synthetic polyacrilonitrile (PAN AN-69) membranes were studied. Leukocyte counts, C3a antigen plasma concentration and whole blood basal and stimulated chemiluminescence (CL) production were determined in blood samples drawn from the fistula before dialysis (T0) and from both the afferent and efferent lines of the dialyser at 15 min (T15) and at the end (Tend) of the dialysis session. This study confirms that, coincident with the nadir of leukopenia observed at T15, dialysis with CUP but not PAN membranes induces a marked rise in C3a antigen levels and profound alterations in whole blood CL production consisting of a dramatic increase in basal CL and a significant loss in CL response capacity to stimulating agents. It further demonstrates that a direct relationship exists between the variations in C3a antigen plasma levels and whole blood CL production observed in the CUP group of patients from T0 to T15 (delta 15) of dialysis. This relationship is characterized by a positive correlation between delta 15 C3a and delta 15 basal CL levels in afferent and efferent lines, and a negative correlation between delta 15 C3a and delta 15 CL response capacity values in the efferent but not afferent line. In contrast, no significant correlation with the type of dialysis membrane could be demonstrated between the variations in polymorphonuclear neutrophil counts and C3a antigen levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Plasma levels of granulocyte elastase during hemodialysis: effects of different dialyzer membranes

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor during hemodialysis were investigated in 15 patients (37.4 +/- 3.2 years) undergoing maintenance hemodialysis (47.0 +/- 12.9 months) with dialyzers made from cellulose hydrate, cuprophan, polymethylmethacrylate, ethylene-vinyl alcohol copolymer, and polyacrylonitrile. Cellulose hydrate membrane caused a maximal increase of the plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI: 1,659.0 +/- 256.8 ng/ml). Patients dialyzed with polyacrylonitrile dialyzers failed to exhibit comparable plasma levels of granulocyte elastase (E-alpha 1PI: 237.8 +/- 22.9 ng/ml). During hemodialysis plasma E-alpha 1PI values rose to a peak 643.0 +/- 174.7 ng/ml in patients on polymethylmethacrylate dialyzers, to 557.5 +/- 120.0 ng/ml on cuprophan dialyzers, but to only 381.9 +/- 54.0 ng/ml on ethylene-vinyl alcohol copolymer dialyzers. Plasma lysozyme levels decreased significantly in the presence of polyacrylonitrile and polymethylmethacrylate membranes. We conclude that the degree of PMNs stimulation depends on the nature of the dialyzer membrane material. The following membranes induce a reaction of increasing intensity: polyacrylonitrile, ethylene-vinyl alcohol copolymer, cuprophan, polymethylmethacrylate, and cellulose hydrate.     

Effect of the hemodialysis membrane on the inflammatory reaction in vivo

BACKGROUND: Increased levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with myocardial infarction, stroke and the development of peripheral arterial disease. Hemodialysis patients show signs of an inflammatory reaction indicated by elevated plasma levels of CRP and by increased plasma levels of interleukins. PATIENTS AND METHODS: To investigate the effect of the dialysis membrane on the inflammatory reaction, we conducted a randomized study in 18 hemodialysis patients. Patients were subsequently treated with dialyzers containing polyamide, polycarbonate or cuprophan for 8 weeks on each dialyzer in a crossover design. During each treatment period, CRP plasma levels were measured 6 times at weekly intervals. The total content and the spontaneous and lipopolysaccharide- (LPS) stimulated production of interleukin-1beta (IL-1beta), IL-6 and IL-1 receptor antagonist (IL-1Ra) were determined in whole blood samples. RESULTS: CRP plasma levels were significantly higher in hemodialysis patients (all patients, 1.63 +/- 0.23 mg/dl) compared to normals (0.14 +/- 0.02 mg/dl, p < 0.0001). CRP levels were lower when patients were dialyzed with polyamide (1.19 +/- 0.18 mg/dl) compared to the levels when the same patients were dialyzed with cuprophan (1.77 +/- 0.37 mg/dl, p = 0.02) or with polycarbonate (1.34 +/- 0.2 mg/dl, n.s). The whole blood content of IL-1Ra in non-incubated samples was significantly lower in normal subjects (512 +/- 60 pg/ml) compared to hemodialysis patients (980 +/- 80 pg/ml, p < 0.01). The whole blood content of IL-1Ra was higher when patients were dialyzed with cuprophan (1,062 +/- 119 pg/ml) compared to the same patients on polyamide (906 +/- 78 pg/ml, p < 0.05) or on polycarbonate (973 +/- 80 pg/ml, n.s.). Spontaneous and LPS-induced production of IL-1beta and IL-6 was similar for all dialyzers. CONCLUSION: We conclude that the inflammatory reaction in hemodialysis patients is affected by the choice of the dialyzer.     

Cuprophan reuse and intradialytic changes of lung diffusion capacity and blood gases

The changes in arterial blood gas, pulmonary function tests, leukocyte counts and complement activation were evaluated during first use and subsequent reuse of cuprophan dialyzers. The dialysate buffer was bicarbonate. Reuse of cuprophan dialyzers significantly attenuated the fall in leukocyte counts and the rise in C3a des Arg seen during first use dialysis. First use dialysis also caused a drop in arterial paO2 from 93.0 +/- 12.4 mm Hg to a nadir of 82.8 +/- 12.6 mm Hg at 60 minutes (P less than 0.01). PaO2 levels did not change when reused dialyzers were employed (93.7 +/- 12.2 before dialysis and 96.4 +/- 15.2 mm Hg at 60 minutes, P greater than 0.05). Intradialytic paO2 curves obtained during first use and reuse were significantly different by variance analysis (P less than 0.001). There was also a significant decline in lung diffusion capacity (DLCO, from 30.70 +/- 8.89 to 23.77 +/- 7.76 ml/min X mm Hg, P less than 0.01) and transfer factor (KCO, from 6.07 +/- 1.97 to 5.65 +/- 2.13 ml/min X mm Hg, P less than 0.01), during first use at one hour after initiation of dialysis. This decrease was entirely prevented during reuse, (P less than 0.001 vs. first use by variance analysis). Percentual changes in leukocyte counts and C3a des Arg concentration on one hand, and in paO2, DLCO and KCO on the other were significantly correlated to each other. Other factors with a possible influence on intradialytic pulmonary function such as ultrafiltration volume, dialysate buffer composition, evolution of intradialytic blood pH and cardiac output, were all identical under both experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polymorphonuclear leukocyte function during hemodialysis: relationship to complement activation

Phagocytosis, H2O2 production, and C3bi receptor (CR3) expression by polymorphonuclear leukocytes (PMN) obtained from patients before, during, and after a hemodialysis treatment were evaluated by flow microfluorometry. The results were compared to changes in plasma levels of C3ades Arg and C5ades Arg. Prior to hemodialysis C3ades Arg and C5ades Arg levels, CR3 expression and phagocytosis were not different from normal controls. However, both basal and phagocytosis-induced H2O2 production were increased. C3ades Arg and C5ades Arg were increased after 15 min of dialysis; this was accompanied by transient but significant reductions in PMN count and phagocytosis and increased CR3 expression. No changes in basal or stimulated H2O2 production were observed. We conclude that PMN of hemodialysis patients are primed for an enhanced respiratory burst before dialysis is initiated. Dialysis-induced complement activation after the initiation of dialysis does not further stimulate H2O2 production or enhance the response to phagocytosis. However, complement activation may cause leukopenia and CR3 expression.