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A complex array of inflammatory mediators are generated as a consequence of blood contact with hemodialysis (HD) membranes. Beside complement activation, other mediators are involved in cell activation, and are thought possibly to be responsible for early and long-term multiple changes in immunity infection, hypercatabolism, beta 2-microglobulin generation and hemostatic mechanisms. Previous studies from our laboratories have established platelet activating factor (PAF) as one of the mediators generated by complement-dependent or independent mechanisms of cell interaction with hemodialysis membranes. Recent studies on the production of PAF from endotoxin-primed polymorphonuclear neutrophils in a closed miniaturized circuit, and on the effect of PAF in mediating endotoxin- and cytokine-induced leukocyte adherence to HD membranes, highlight so far undescribed new roles of this mediator in biocompatibility.

In the present study we evaluated spontaneous and stimulated adherence of human monocytes to regenerated cellulose and polyacrylonitrile (AN69) membranes. Spontaneous adherence at 60 min was significantly higher for regenerated cellulose (28 +/- 2%, P < 0.001) than for AN69 (11 +/- 2) membranes. Stimuli such as bacterial lipopolysaccharide, TNF alpha, interleukin-1 and -6 as well as platelet-activating factor, but not IL-4, significantly enhanced adherence at 60 min to AN69 (28 to 30%). In contrast, adherence was not further inducible in the presence of regenerated cellulose. Both spontaneous and cytokine/bacterial lipopolysaccharide-stimulated adherence were significantly reduced by SDZ-63072, a specific platelet-activating factor receptor antagonist. This difference in sensitivity of monocyte adherence reflects probably the intrinsic ability of regenerated cellulose to provide maximal spontaneous monocyte adhesion. These data suggest that PAF may act as an adherence mediator. This is in line with the ability of regenerated cellulose to directly stimulate monocytes to synthesize platelet-activating factor and with the ability of cytokines and bacterial lipopolysaccharide to stimulate its synthesis. Although AN69 has a low adherence potential, bacterial lipopolysaccharide or cytokines may blunt the biocompatibility of this membrane.

BK-PMMA 2.1 m2 surface dialysers were used in vivo and in vitro for evaluation of their capacity for beta 2-M removal by both adsorption and elimination through the membrane. As expected, in vivo, beta 2-M plasma concentrations were more effectively reduced when the dialyser was used in haemofiltration, rather than in haemodialysis. However, the mass recovered in the ultrafiltrate could not account for the observed difference in beta 2-M removal. In vitro tests demonstrated that membrane adsorption of beta 2-M is greater when the dialyser is used in convection than in diffusion. Therefore, the greater beta 2-M removal during haemofiltration depends on both increased adsorption and membrane elimination by convection. Thanks to adsorption, beta 2-M removal by haemodialysis was greater than for other synthetic membranes, but was insufficient to obtain beta 2-M removal corresponding to the estimated generation.