title: Active inhibitory effect of nafamostat mesylate against the elevation of plasma myeloperoxidase during hemodialysis.
abstract: Plasma levels of myeloperoxidase (MPO) were compared between hemodialysis (HD) sessions using heparin and those using nafamostat mesylate (NM) as an anticoagulant by an enzyme immunoassay established in our laboratory. MPO levels were markedly elevated during the entire HD procedure with heparin. In contrast, MPO levels were scarcely elevated during the HD with NM. On the other hand, polymorphonuclear leukocyte-elastase was markedly elevated during both of these HD procedures. These observations indicated that NM selectively attenuated MPO elevation in vivo during HD. This inhibitory effect of NM was further investigated ex vivo. Blood samples from a normal subject were collected with heparin alone, NM alone and a mixture of heparin and NM. Each sample was then circulated in a closed circuit composed of a dialyzer with a cuprophane membrane. MPO levels with heparin alone were shown to markedly rise in the closed system. In contrast, levels of MPO in the blood samples mixed with NM were not elevated even in the presence of heparin. These ex vivo results indicate that NM has an active inhibitory effect on the elevation of plasma MPO induced by granulocyte activation through a dialysis membrane. Our results demonstrate that clinical use of NM as an anticoagulant serves to selectively suppress MPO elevation considered as a consequence of granulocyte activation during HD.
authors.affiliation: Center for Kidney Disease, Toho Hospital, Gunma, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inose
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: A
authors.initials: A
authors.lastname: Tsutida
authors.forename: M
authors.initials: M
authors.lastname: Onai
authors.forename: M
authors.initials: M
authors.lastname: Komai
authors.forename: K
authors.initials: K
authors.lastname: Uehara
authors.forename: S
authors.initials: S
authors.lastname: Yano
authors.forename: T
authors.initials: T
authors.lastname: Naruse
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000925:Anticoagulants / Q000494:pharmacology*; D001550:Benzamidines; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D001550:Benzamidines; D006146:Guanidines; D009195:Peroxidase; D019272:Leukocyte Elastase; C032855:nafamostat