BIOINCOMPATIBILITY - PERSPECTIVES IN 1993

Bioincompatibility reactions related to the non-physiology of the proc edure have plagued dialysis from its early days. Although the problem is certainly multifactorial, the present overview selectively focuses on some aspects of activation of late complement (C) components, the i mportance of which may have been underappreciated in the past. Dialysi s patients are poised for intense C activation because of cumulation o f the low molecular weight factor D, an intrinsically active serine es terase which is not inhibited by any known endogenous inhibitor and ca talyzes an early step in the alternative pathway. C activation reflect s the net balance between activation and inhibition, the latter partic ularly via factor H binding. Dialyzer membrane characteristics that ar e related to factor H binding and regulation of initial activation ste ps include not only membrane surface chemistry but also its microdomai n structure. Kinetic studies of the generation of the terminal complem ent complex (TCC) suggest ongoing generation throughout the duration o f a dialysis session (in contrast to the transient release of C-derive d anaphylatoxins). Potential consequences of TCC generation include am plification of the non-C-dependent cell activation signals through L-f ucose-dependent steps. Efforts to reduce TCC generation by membrane en gineering, for example, end group derivatization and optimization of m icrodomain structure, open perspectives for the development of more bi ocompatible membranes.