acetylcellulose and Leukopenia

Topics: Acrylic Resins; Animals; Biocompatible Materials; Cellulose; Complement Activation; Humans; Kidneys, Artificial; Leukopenia; Lung Diseases; Membranes, Artificial; Methylmethacrylates; Renal Dialysis

The study is a comparison of 4 successive hemodialysis (HD) sessions on each patient, 2 with cuprophan (CU) membrane (Gambro 120 M) and 2 with Cellulose acetate (CA) (Cordis Dow 3500). 60 minutes prior to the HD session placebo or Ticlopidine (500 mg) was administered orally to each patient. Leucocyte and platelet counts, serum C3 complement, arterial PO2, PCO2 and PH were measured before and 15, 30, 60, 120 and 240 minutes after the beginning of HD. Leucocyte count fell markedly within 15 minutes of both placebo HD sessions, but it was significantly lower (p less than 0.005) in CA than CU membrane. Ticlopidine prevented significantly (p less than 0.01) the HD-induced leucopenia. Slight changes in platelet count, either in placebo or Ticlopidine study were observed. Serum C3 complement increased significantly (p less than 0.05) at 15 minutes of CU placebo session and was also correlated (p less than 0.01) with the concurrent leucopenia. The arterial PO2 decreased 22% and 13.5% during HD with CU and CA membranes respectively, but it was preserved within normal limits by Ticlopidine. The arterial PH was increased up to 7.4 at the end of all HD sessions, while PCO2 showed only slight changes. We conclude that: 1) CA membrane is better tolerated than CU 2) HD-induced leucopenia and hypoxemia are prevented by Ticlopidine, probably by modulating the complement activation.

Topics: Adult; Aged; Biocompatible Materials; Cellulose; Complement Activation; Female; Humans; Hypoxia; Leukopenia; Male; Middle Aged; Renal Dialysis; Ticlopidine

The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investigating the effects of these membranes on complement function in vitro. Whereas from in vivo studies no definite conclusions could be drawn, in vitro investigations provided clear-cut information. When more sophisticated technical approaches were undertaken, it became evident that hemodialysis leukopenia has to be thought of in terms of chemotactic factor generation. In fact, a strict correlation was demonstrated between the degree of leukopenia induced by the dialyzers tested and the ability of the relative membrane to generate chemotactic activity in vitro. Moreover, the previously observed ability of polyacrilonitrile membrane to induce a decrement in complement function was due to the ability of polyacrilonitrile to adsorb complement activity and did not correspond to effective complement consumption. This finding explained why polyacrilonitrile dialysis is not accompanied by a decrease in circulating granulocytes. Taken together, our data strongly point to a pivotal role of complement system in the pathogenesis of hemodialysis leukopenia.

Topics: Acrylic Resins; Acrylonitrile; Cellulose; Chemotactic Factors; Complement Activation; Complement C3; Complement Factor B; Complement System Proteins; Female; Humans; Immunoelectrophoresis; Kidneys, Artificial; Leukopenia; Male; Membranes, Artificial; Renal Dialysis; Time Factors

Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-cellulose, 1.8 m2 for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-alpha1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs acetate cellulose). In the presence of fresh plasma, as source of complement, the differences between acetate cellulose vs polysulfone and benzyl-cellulose were even more evident, suggesting the role of complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of leukopenia was at 15 and 30 min with acetate-cellulose (79%) and benzyl-cellulose (50%) (p<0.05 acetate- vs benzyl-cellulose) and at 15 min with polysulfone (24%) (p<0.01 vs acetate- and benzyl-cellulose). Plasma C3a des Arg levels arose to 2037 +/- 120 ng/ml, 1216 + 434 ng/ml and 46 +/- 55 ng/ml with acetate-, benzyl-cellulose and polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of TNF-alpha was detected with any of three membranes. Clearance values of urea, creatinine and uric acid were superimposable for all the three membranes. However, benzyl cellulose had a significantly higher clearance for phosphorus (normalized for surface area) (p<0.01 vs acetate-cellulose, 0.001 vs polysulfone). These results implicate that synthetic modification of the cellulose polymer as for the benzyl-cellulose significantly reduces the in vitro adherence, delays the in vivo activation of "classic" biocompatibility p

Topics: Aged; Aged, 80 and over; Anaphylatoxins; Biocompatible Materials; Blood Cell Count; Cell Adhesion; Cellulose; Complement C3a; Humans; In Vitro Techniques; Kidney Failure, Chronic; Leukopenia; Membranes, Artificial; Middle Aged; Monocytes; Neutrophils; Pancreatic Elastase; Phosphates; Polymers; Renal Dialysis; Sulfones

The effect of blood-membrane interaction on several biocompatibility parameters has been investigated. Four groups of healthy subjects underwent sham hemodialysis, i.e. the establishment of blood-dialysis membrane contact, but without circulating dialysate, using cellulose-based membranes (regenerated cellulose and cellulose acetate) or synthetic membranes (polysulfone and polyacrilonitrile). Contact between blood and cellulose-based membranes resulted in pronounced complement activation and leukopenia whereas contact between blood and synthetic membranes induced weak complement reaction. The release of granulocytic elastase comparable to that obtained during clinical dialysis seemed to correlate directly with the types of membrane used. The gradual increase in the level of plasma elastase during blood-membrane contact, as opposed to the transient nature of the increase in the levels of complement, suggests that different mechanisms are responsible for these reactions. Nutritional implications of dialysis membrane bioincompatibility are discussed in the light of recently published metabolic data obtained in these subjects.

Topics: Acrylic Resins; Acrylonitrile; Adult; Alkanesulfonates; Biocompatible Materials; Blood Physiological Phenomena; Blood Platelets; Cell Size; Cellulose; Complement Activation; Complement C3a; Fasting; Humans; Leukopenia; Membranes, Artificial; Middle Aged; Pancreatic Elastase; Polymers; Renal Dialysis; Sulfones

The effects of hemodialysis (HD) on the levels of serum amyloid A (SAA), C-reactive protein (CRP) and interleukin-1 beta (IL-1 beta) were studied in 8 patients. Bicarbonate dialysate was used exclusively, and three different membranes, Cuprophan (CU), cellulose acetate (CA), and polymethylmetachrylate (PMMA) were compared. The SAA levels increased significantly with each membrane. With CU, they rose from 4.0 +/- 2.0 (mg/l, mean +/- SEM) to 9.6 +/- 2.8 at 60 min and to 15.0 +/- 4.9 at 240 min. The values with CA were 3.8 +/- 2.1, 15.3 +/- 5.6, and 23.8 +/- 3.9; and with PMMA 2.4 +/- 1.3, 12.1 +/- 5.6, and 12.1 +/- 5.9, respectively. The alterations of SAA neither correlated with the weight loss nor the increase of serum albumin during dialysis. The CRP values showed insignificant changes. The IL-1 beta levels rose with CU from 87 +/-18 (ng/l) to 155 +/- 33 at 60 min and to 172 +/- 47 at 240 min. With CA, the values were 67 +/- 14, 198 +/- 46, and 121 +/- 23, and with PMMA 63 +/- 13, 246 +/- 93, and 211 +/- 86, respectively. These results did not correlate with the effects of the membranes on complement activation. It is concluded that the release of cytokines during HD apparently leads to a rapid synthesis of acute-phase proteins as a sign of inflammation. Thus, SAA may be used as one indicator of the biocompatibility of HD treatment.

Topics: Adult; Aged; C-Reactive Protein; Cellulose; Complement Activation; Cytokines; Female; Humans; Inflammation; Interleukin-1; Leukopenia; Male; Membranes, Artificial; Methylmethacrylates; Middle Aged; Renal Dialysis; Serum Amyloid A Protein

The goal of these prospective studies was to determine the effect of different dialyzer membranes and dialysate composition on leukopenia and hypoxemia during hemodialysis with citrate anticoagulation. Significant early leukopenia was found with a cuprophane membrane, while a cellulose acetate membrane was associated with mild early leukopenia. Bath composition had no effect. Bicarbonate dialysate, compared with acetate, eliminated hypoxemia in cellulose acetate membranes and reduced its degree and duration with cuprophane. Membrane composition had no effect on hypoxemia during acetate dialysis. The findings indicate that leukopenia is directly and exclusively related to membrane composition while hypoxemia only relates in part to membrane effects. Serial determinations of complement components C3a and C5a showed significant increases in parallel with leukopenia during heparin anticoagulation, but the anaphylatoxin concentration changes were dissociated during dialysis with citrate anticoagulation. The concentrations of anaphylatoxins C3a and C5a appear not to be directly related to dialysis-induced leukopenia. The dissociation between anaphylatoxin concentrations and leukopenia may be related to changes in generation or unmasked changes in leukocyte response. Citrate anticoagulation may provide a useful probe for further studies on membrane-leukocyte interactions in vivo.

Topics: Acetates; Anaphylatoxins; Anticoagulants; Bicarbonates; Calcium; Cellulose; Citrates; Citric Acid; Complement Activation; Complement C3; Complement C3a; Complement C5; Complement C5a; Heparin; Humans; Hypoxia; Leukocyte Count; Leukopenia; Male; Membranes, Artificial; Oxygen; Peptide Biosynthesis; Potassium; Prospective Studies; Renal Dialysis; Sodium

An interest in hemodialysis-related patient symptomatology dating back to the beginnings of maintenance hemodialysis (HD) therapy prompted our investigations to determine the etiology of such discomfort. Since the discovery by Craddock et al (1) of the activation of the alternative complement pathway by hemodialyzer membrane, our efforts toward defining the relationship of symptoms to complement activation have been done in collaboration with the Minnesota group. Results of an earlier blinded study, (2) and continuing investigations of HD membranes provide data which support the contention that complement activation, although not necessarily etiologic in the symptoms related to dialysis, serves as an indicator of membrane compatibility. These newer data reveal C3a rises in vivo and in vitro by a Japanese processed cuprammonium membrane for dialysis to be similar to cuprophane. In vivo C3a elevation using Travenol CA-110 hemodialyzers of cellulose acetate are significantly lower and are similar to earlier results obtained by cellulose acetate of CD manufacture.

Topics: Cellulose; Complement Activation; Complement C3; Complement C3a; Humans; In Vitro Techniques; Kidneys, Artificial; Leukopenia; Materials Testing; Renal Dialysis

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.

Topics: Acrylic Resins; Cellulose; Complement Activation; Complement C3; Complement C3a; Humans; Hypersensitivity; Kidneys, Artificial; Leukopenia; Membranes, Artificial; Radioimmunoassay; Renal Dialysis

Topics: Acrylic Resins; Cellulose; Complement Activation; Humans; Leukopenia; Membranes, Artificial; Renal Dialysis

In a study on polymorphonuclear leucocyte (PMN) chemotaxis and random locomotion carried out on 16 patients undergoing haemodialysis and on the same functions in normal PMN which were separated from plasma and subjected to laboratory haemodialysis, it was shown that random PMN locomotion is reduced and that there is a concomitant fall in the leucocyte count in haemodialyzed patients. The laboratory haemodialysis demonstrated that serum factors were not responsible for the PMN dysfunction, which lasted for the entire period of the procedure. The changes were observed only when cellulose membranes were used, and not when haemodialysis was performed with polyacrilonitrile membranes. The reduction in random PMN locomotion may be involved in the genesis of dialysis leucopenia, as well as in the increased susceptibility of uremic patients to infections.

Topics: Cell Movement; Cellulose; Chemotaxis, Leukocyte; Complement C3; Complement C3d; Humans; Kidney Failure, Chronic; Leukopenia; Membranes, Artificial; Neutrophils; Renal Dialysis

Acute, transient leucopenia occurs in uraemic patients during the first minutes of haemodialysis, haemofiltration and ultrafiltration, and this leucopenia depends on the membrane used: maximal with cuprophan, less marked using cellulose acetate in haemofiltration and minimal with polyacrylonitrile. Complement activation was noted in all dialysis procedures except ultrafiltration. However, no correlation was found between the intensity of the complement activation and the degree of leucopenia. Significant hypoxia only appeared in haemodialysis using an acetate bath even with the polyacrylonitrile membrane. Sequential ultrafiltration-dialysis studies clearly demonstrate that leucopenia and hypoxia are unrelated effects of haemodialysis. Leucopenia depends on the membrane used and hypoxia may be related to the use of an acetate dialysate. In addition, the presence of dialysis fluid was necessary for membrane-induced complement activation suggesting an important influence of the dialysate on membrane biocompatibility.

Topics: Acetates; Acrylic Resins; Adolescent; Adult; Blood; Cellulose; Complement Activation; Humans; Kidney Failure, Chronic; Kidneys, Artificial; Leukopenia; Membranes, Artificial; Middle Aged; Oxygen; Renal Dialysis; Time Factors; Ultrafiltration