Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis

Mareille Gritters, Muriël P C Grooteman, Margreet Schoorl, Marianne Schoorl, Piet C M Bartels, Peter G Scheffer, Tom Teerlink, Casper G Schalkwijk, Marieke Spreeuwenberg, Menso J Nubé

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)153-9
Number of pages7
JournalNephrology, Dialysis, Transplantation
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2006

Cite this

Gritters, Mareille ; Grooteman, Muriël P C ; Schoorl, Margreet ; Schoorl, Marianne ; Bartels, Piet C M ; Scheffer, Peter G ; Teerlink, Tom ; Schalkwijk, Casper G ; Spreeuwenberg, Marieke ; Nubé, Menso J. / Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis. In: Nephrology, Dialysis, Transplantation. 2006 ; Vol. 21, No. 1. pp. 153-9.
@article{0201a6311f734a879ffec75a152a4b0c,
title = "Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis",
abstract = "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.",
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author = "Mareille Gritters and Grooteman, {Muri{\"e}l P C} and Margreet Schoorl and Marianne Schoorl and Bartels, {Piet C M} and Scheffer, {Peter G} and Tom Teerlink and Schalkwijk, {Casper G} and Marieke Spreeuwenberg and Nub{\'e}, {Menso J}",
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Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis. / Gritters, Mareille; Grooteman, Muriël P C; Schoorl, Margreet; Schoorl, Marianne; Bartels, Piet C M; Scheffer, Peter G; Teerlink, Tom; Schalkwijk, Casper G; Spreeuwenberg, Marieke; Nubé, Menso J.

In: Nephrology, Dialysis, Transplantation, Vol. 21, No. 1, 01.2006, p. 153-9.

Research output: Contribution to journalArticleAcademicpeer-review

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

VL - 21

SP - 153

EP - 159

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 1

ER -