Reduction of neutrophil activation by vitamin E modified dialyzer membranes

Background/Aim: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dailysis membrane, bu t the mechanism remains unclear. We studied the mechanism of neutrophilic a ctivation by comparing a vitamin E modified membrane (CLEE) and a regular c ellulose membrane (CLSS). Methods: (1) CLSS and GLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia , CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulate d through GLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivat ed; heating: alternative pathway inactivated; control: no modification) wer e incubated in the CLSS minimodel, and the neutrophilic activation was comp ared. Results: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when GLEE membrane s were used. The same tendency was observed in minimodels. However, the deg rees of inhibition in clinical dialysis, especially at the venous line, wer e significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both cl assical and alternative pathways were inactivated or when the classical pat hway alone was inactivated, but were not significantly different when the a lternative pathway alone was inactivated. Conclusions: Vitamin E modificati on of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the cl inical situation than in ex vivo models, suggesting a possible effect of vi tamin E in inhibiting bioreactions due to pyrogen in the dialysate. The cla ssical complement pathway is required in membrane-induced neutrophilic acti vation, at least during the initial stage. Copyright (C) 2000 S. Karger AG, Basel.