title: The favorable effect of regional citrate anticoagulation on interleukin-1beta release is dissociated from both coagulation and complement activation.
abstract: BACKGROUND
  It has been claimed that regional citrate anticoagulation (RCA) improves unfavorable calcium and magnesium dependent cellular and humoral events due to blood/dialyzer membrane interactions during hemodialysis (HD). This study aimed to verify whether the favorable effect of RCA on biocompatibility is independent from coagulation pathway modulation.
  
  
  METHODS
  A randomized controlled cross-over single blind trial comparing the activity of the coagulation pathway (thrombinantithrombin complexes (TAT), fibrinopeptide A (FPA), prothrombin fragments 1+2 (F 1+2) and D-dimer (DD)), complement activation (C3a) and interleukin-1 beta secretion (IL-1beta) in nine chronic HD patients treated with RCA or heparin. Blood samples were obtained from the arterial (C3a, IL-1beta, TAT, F 1+2, FPA and DD) and venous (TAT, F 1+2, FPA) lines 2 min after starting treatment and repeatedly during the procedure after 15 min (C3a and IL-1beta), 30 min (C3a), 45 (C3a) and 180 min (TAT, F 1+2, FPA and DD).
  
  
  RESULTS
  In both treatment protocols significant enhancement was observed in the coagulation activity during the dialysis session, documented by an increase in TAT (p<0.001), F 1+2 (p<0.001) and FPA (p=0.001). Comparing the two anticoagulation modalities, no differences were noticed in the activity of the coagulation pathway, but a significantly higher complement activity (C3a=886 (832-908) vs. 770 (645-857) ng/mL, p<0.05) and lower IL-1beta secretion (235 (206-285) vs. 538 (346-974) pg/mL, p<0.05) was observed in RCA.
  
  
  CONCLUSIONS
  Due to an RCA protocol guaranteeing the same extent of anticoagulation activation as standard heparin, we demonstrated that the significantly lower IL-1beta secretion obtained with RCA is independent from the anticoagulation modulation and dissociated from the complement activity.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Carità Hospital, Locarno, Switzerland. lugabutti@swissonline.ch
authors.forename: Luca
authors.initials: L
authors.lastname: Gabutti
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrari
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mombelli
authors.forename: Franco
authors.initials: F
authors.lastname: Keller
authors.forename: Claudio
authors.initials: C
authors.lastname: Marone
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III; D001777:Blood Coagulation / Q000187:drug effects*; D002951:Citrates / Q000627:therapeutic use*; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism / Q000628:therapy; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D006435:Renal Dialysis; D016037:Single-Blind Method
chemical_list: D000925:Anticoagulants; D002951:Citrates; D007375:Interleukin-1; D010446:Peptide Fragments; D011498:Protein Precursors; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D015926:Complement C3a; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases