Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis.
BACKGROUND
Haemodialysis (HD)-induced bio-incompatibility includes alterations in both cellular elements and humoral factors. As far as polymorphonuclear (PMN) cells are concerned, an increase in both adhesion and degranulation has been reported. However, whereas increased PMN adherence and aggregation is highly linked with early transient complement activation, degranulation seems a continuous process, independent from the formation of complement degradation products. In the process of cell activation, including PMN degranulation, divalent cations (Ca2+) appear to play a pivotal role. As regionally administering citrate creates an almost Ca(2+)-free environment within the dialyser, it is tempting to speculate that Ca2+ dependent phenomena of bio-incompatibility, originating within the dialyser, can be attenuated by substituting conventional heparin for citrate.


METHODS
Therefore, both anticoagulation modalities were compared in 10 stable patients, undergoing haemodialysis (HD) treatment with cellulose-triacetate membranes (CTA) only. Apart from the intracellular granule products myeloperoxidase (MPO) and lactoferrin (LF), the classical parameters of bio-incompatibility, peripheral blood neutropenia and complement activation, were measured.


RESULTS
Analysis of MPO and LF gradients across the dialyser (concentration in efferent line-concentration in afferent line) suggested that degranulation is an early process, that occurs mainly within the extracorporeal circuit. Citrate abolished the release of MPO almost completely, whereas LF release was partially inhibited. Neither neutropenia, nor complement activation could be correlated with the occurrence of degranulation.


CONCLUSIONS
HD-induced PMN degranulation seems largely independent from complement activation, but primarily reliant on Ca2+, at least in the case of CTA membranes.
Bos
J C
JC
Department of Nephrology, Medical Centre Alkmaar, The Netherlands.
Grooteman
M P
MP
van Houte
A J
AJ
Schoorl
M
M
van Limbeek
J
J
Nubé
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D019343:Citric Acid / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007781:Lactoferrin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D006435:Renal Dialysis
D000925:Anticoagulants; D019343:Citric Acid; D006493:Heparin; D009195:Peroxidase; D007781:Lactoferrin; D002118:Calcium