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

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-1β) in nine chronic HD patients treated with RCA or heparin. Blood samples were obtained from the arterial (C3a, IL-1β, 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-1β), 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-1β 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-1β secretion obtained with RCA is independent from the anticoagulation modulation and dissociated from the complement activity.