TY - JOUR
T1 - Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis
AU - Gritters, Mareille
AU - Grooteman, Muriël P C
AU - Schoorl, Margreet
AU - Schoorl, Marianne
AU - Bartels, Piet C M
AU - Scheffer, Peter G
AU - Teerlink, Tom
AU - Schalkwijk, Casper G
AU - Spreeuwenberg, Marieke
AU - Nubé, Menso J
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anticoagulants/therapeutic use
KW - Blood Platelets/drug effects
KW - Cell Degranulation/drug effects
KW - Cholesterol, LDL/blood
KW - Citrates/therapeutic use
KW - Cross-Over Studies
KW - Dalteparin/therapeutic use
KW - Female
KW - Heparin/therapeutic use
KW - Humans
KW - Kidney Failure, Chronic/diagnosis
KW - Lipoproteins, LDL/blood
KW - Male
KW - Middle Aged
KW - Neutrophils/drug effects
KW - Oxidative Stress
KW - Probability
KW - Reference Values
KW - Renal Dialysis/adverse effects
KW - Sensitivity and Specificity
KW - Statistics, Nonparametric
U2 - 10.1093/ndt/gfi069
DO - 10.1093/ndt/gfi069
M3 - Article
C2 - 16144857
VL - 21
SP - 153
EP - 159
JO - Nephrology, Dialysis, Transplantation
JF - Nephrology, Dialysis, Transplantation
SN - 0931-0509
IS - 1
ER -