Reduction of neutrophil activation by vitamin E modified dialyzer membranes.
OBJECTIVE
Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dialysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS).


METHODS
(1) CLSS and CLEE 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 circulated through CLEE 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 inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared.


RESULTS
In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated.


CONCLUSIONS
Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.
Omata
M
M
Kidney Center, Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Higuchi
C
C
Demura
R
R
Sanaka
T
T
Nihei
H
H
D000328:Adult; D000368:Aged; D002482:Cellulose; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007688:Kidneys, Artificial / Q000009:adverse effects; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects; D014810:Vitamin E
D016177:Macrophage-1 Antigen; D014810:Vitamin E; D015926:Complement C3a; D002482:Cellulose; D009195:Peroxidase