The favorable effect of regional citrate anticoagulation on interleukin-1beta 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-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.
Gabutti
Luca
L
Division of Nephrology, Department of Internal Medicine, Carità Hospital, Locarno, Switzerland. lugabutti@swissonline.ch
Ferrari
Nicola
N
Mombelli
Giorgio
G
Keller
Franco
F
Marone
Claudio
C
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
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