Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis.
BACKGROUND
During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation, most probably due to its calcium chelation ability.


METHODS
In the present study, apart from HD-induced PMN and platelet degranulation, oxidative stress was analysed during three modes of anticoagulation. Heparin, dalteparin and citrate (HDhep, HDdal and HDcit) were compared in a randomized, crossover fashion in eight chronic HD patients. Multiple blood samples were taken during the third HD session of each modality, from both the afferent and efferent line. Besides the degranulation markers MPO and PF4, various markers of oxidative stress were measured, including oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) and carboxymethyllysine (CML).


RESULTS
During HDhep and HDdal, marked degranulation was observed shortly after the start of HD. In contrast, during HDcit, PF4 and MPO levels remained unaltered, suggesting no release at all. After 1 week of HDcit, ox-LDL levels were markedly reduced [median 26% (3-65%), P=0.01], if compared with HDhep and HDdal. As regards MDA and CML, no differences were found.


CONCLUSIONS
This study shows first, that HD-induced PMN and platelet degranulation are early, most probably calcium-dependent processes and, secondly, that the formation of ox-LDL is clearly dependent on the type of anticoagulant applied.
Gritters
Mareille
M
Department of Nephrology, Medical Center Alkmaar, and VU University Medical Center, Amsterdam, The Netherlands. mareillegritters@hotmail.com
Grooteman
Muriël P C
MP
Schoorl
Margreet
M
Schoorl
Marianne
M
Bartels
Piet C M
PC
Scheffer
Peter G
PG
Teerlink
Tom
T
Schalkwijk
Casper G
CG
Spreeuwenberg
Marieke
M
Nubé
Menso J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D002951:Citrates / Q000627:therapeutic use; D018592:Cross-Over Studies; D017985:Dalteparin / Q000627:therapeutic use; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D011336:Probability; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D000925:Anticoagulants; D008078:Cholesterol, LDL; D002951:Citrates; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006493:Heparin; D017985:Dalteparin