The favorable effect of regional citrate anticoagulation on interleukin-1beta release is dissociated from both coagulation and complement activation

J Nephrol. Nov-Dec 2004;17(6):819-25.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / therapeutic use*
  • Antithrombin III
  • Blood Coagulation / drug effects*
  • Citrates / therapeutic use*
  • Complement Activation / drug effects*
  • Complement C3a / metabolism
  • Fibrinopeptide A / metabolism
  • Humans
  • Interleukin-1 / metabolism*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / therapy
  • Peptide Fragments / blood
  • Peptide Hydrolases / blood
  • Protein Precursors / blood
  • Prothrombin
  • Renal Dialysis*
  • Single-Blind Method


  • Anticoagulants
  • Citrates
  • Interleukin-1
  • Peptide Fragments
  • Protein Precursors
  • antithrombin III-protease complex
  • Fibrinopeptide A
  • prothrombin fragment 1
  • prothrombin fragment 2
  • Complement C3a
  • Antithrombin III
  • Prothrombin
  • Peptide Hydrolases