Dialysis membranes complement-activating

Complement activation by dialysis membranes may be related in part to the availability of surface hydroxyl groups, particularly on cellu-losic membranes. Complement activation may be greatly attenuated by the use of other membrane materials such as polysulfone and polycarbonate. Complement activation by biomaterial membranes has been reviewed [27]. 

With either type of dialysis, studies suggest that recovery of renal function is decreased in ARF patients who undergo dialysis compared with those not requiring dialysis. Decreased recovery of renal function may be due to hemodialysis-induced hypotension causing additional ischemic injury to the kidney. Also, exposure of a patient s blood to bioincompatible dialysis membranes (cuprophane or cellulose acetate) results in complement and leukocyte activation which can lead to neutrophil infiltration into the kidney and release of vasoconstrictive substances that can prolong renal dysfunction.26 Synthetic membranes composed of substances such as polysulfone, polyacrylonitrile, and polymethylmethacrylate are considered to be more biocompatible and would be less likely to activate complement. Synthetic membranes are generally more expensive than cellulose-based membranes. Several recent meta-analyses found no difference in mortality between biocompatible and bioincompatible membranes. Whether biocompatible membranes lead to better patient outcomes continues to be debated. 

Another issue relating to dialysis membranes is their ability to stimulate the immune system. If the dialysis filter membrane does not activate the complement system (C3a and C5a) when it comes in contact with the patient s blood, it is considered biocompatible. In the acute setting, the incidence of hypotension, fever, bronchoconstric-tion, and thrombocytopenia are lower in patients dialyzed with biocompatible filters. The most biocompatible dialyzers use a synthetic membrane of PS, PAN, or PMMA. Although not definitive, biocompatible membranes may be associated with fewer adverse events during dialysis, lower rates of hospitalization, reduced death rates, and slower declines in residual renal function. ... 

Another cause of dialysis-induced hypoxemia is the use of bioincompatible dialyzer membranes, which activate complement (C3 and C5). This causes the formation of C3a and C5a, which are chemotactic for neutrophils and are ana-phylatoxic, thereby causing pulmonary sequestration of neutrophils and platelets (hence neutropenia and thrombocytopenia), with resultant ventilation-perfusion (V/Q) mismatch and hypoxemia. This is evidenced by the simultaneous development 15 minutes after the start of dialysis of hypoxemia, neutropenia, and high circulating levels of C3a and C5a (C2). 

Ivanovich, R, Chenoweth, D., Schmidt, R., Klinkmann, H., Boxer, L., Jacob, H., Hammerschmidt, D. Symptoms and activation of granulocytes and complement with two dialysis membranes. Kidney Int. 24, 758-763 (1983)... 

While transport properties play an important role in the selection of a dialyzer membrane, an equally important consideration in the evolution of the dialyzer technology has been biocompatibility, or the compatibility of the dialyzer with blood. Three aspects of biocompatibility that are important in dialysis are clotting, activation of the complement cascade, and cytokine generation. 

Complement Activation Complement proteins are so-named because they complement antibody activity to eliminate pathogens. The alternate pathway of the complement cascade is normally activated by bacterial surface molecules. Complement activation during dialysis was first identified by the rapid drop in white blood cell counts (neutropenia) during the first 30 min of dialysis. Regenerated cellulose membranes activate complement through the alternate pathway (Chenoweth et al., 1983). Modified cellulose membranes approach the biocompatibility profile of synthetic materials in terms of neutropenia and complement activation. 

---