Citrate anticoagulation does not correct cuprophane bioincompatibility as evaluated by the expression of leukocyte surface molecules.
BACKGROUND
Citrate, used for the anticoagulation of the extracorporeal dialysis circuit, reduces ionized calcium by chelation and has been claimed to attenuate dialyser membrane bioincompatibility. Dialysis with complement-activating cuprophane membranes is associated with leukopenia which has been related to an increase in adhesion molecule expression on the surface of circulating leukocytes.


METHODS
The effect of citrate anticoagulation on the expression of CD11b, CD11c and CD45 on the surface of granulocytes and CD14 on monocytes during haemodialysis with cuprophane membranes, was evaluated by flow cytometric analysis. A comparison of standard heparin vs citrate was performed in 14 chronic haemodialysis patients. During citrate anticoagulation a calcium-free dialysate was used and citrate was infused to obtain a concentration of 4.3 mmol/l blood. The unchallenged 'baseline state' expression of the surface molecules and the increase after ex vivo stimulation with phorbol 12-myristate 13-acetate (delta-PMA) or formyl-methionyl-leucyl-phenylalanine (delta-fMLP) was studied.


RESULTS
With heparin, as well as with citrate, a sharp fall in granulocyte and monocyte count was observed after 15 min of dialysis, followed by a recovery at the end of the session. The expression of CD11b, CD11c and CD45 on granulocytes increased markedly during cuprophane dialysis with a peak at 15 min; there were no differences in response between heparin and citrate anticoagulation. Delta-PMA and delta-fMLP for CD45, CD11c and CD14 showed a decrease during cuprophane dialysis vs t0; again there were no differences between heparin and citrate.


CONCLUSIONS
We conclude that the use of citrate was not associated with reduced leukocyte activation as measured by the expression of surface molecules during cuprophane dialysis and that no effect on dialysis leukocytopenia could be registered.
Department of Internal Medicine, University Hospital, Gent, Belgium.
A
A
Dhondt
R
R
Vanholder
M A
MA
Waterloos
G
G
Glorieux
R
R
De Smet
N
N
Lameire
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000009:adverse effects*; D002482:Cellulose / Q000009:adverse effects / Q000031:analogs & derivatives*; D019343:Citric Acid / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D007688:Kidneys, Artificial / Q000009:adverse effects; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D008567:Membranes, Artificial; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D006435:Renal Dialysis / Q000009:adverse effects*; D013997:Time Factors
D000925:Anticoagulants; D001672:Biocompatible Materials; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D008567:Membranes, Artificial; D019343:Citric Acid; D002482:Cellulose; C009865:cuprammonium cellulose; D017493:Leukocyte Common Antigens