Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes.
BACKGROUND
Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia.


METHODS
In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl(2) was administered into the dialyzer outlet at 8. 25 mmol Ca(2+)/h (citrate 10 mmol/l) or at 11 mmol Ca(2+)/h (citrate 7 and 10 mmol/l) to reconstitute the calcium levels in the blood returning to the patient.


RESULTS
The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca(2+) concentration and the increase in CD11b and CD11c expression was found.


CONCLUSIONS
Citrate/CaCl(2) administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.
Dhondt
A
A
Renal Division, Department of Internal Medicine, University Hospital, Ghent, Belgium.
Vanholder
R
R
Tielemans
C
C
Glorieux
G
G
Waterloos
M A
MA
De Smet
R
R
Lameire
N
N
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001672:Biocompatible Materials; D002118:Calcium / Q000097:blood; D002482:Cellulose; D002951:Citrates / Q000008:administration & dosage*; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000737:chemistry* / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D007970:Leukopenia / Q000188:drug therapy* / Q000517:prevention & control; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods*; D012964:Sodium / Q000097:blood
D000925:Anticoagulants; D001672:Biocompatible Materials; D002951:Citrates; D016177:Macrophage-1 Antigen; D008567:Membranes, Artificial; D015926:Complement C3a; D002482:Cellulose; D006493:Heparin; D012964:Sodium; D017493:Leukocyte Common Antigens; D002118:Calcium