#2668 SUPERIOR BIOCOMPATIBILITY OF REGIONAL CITRATE ANTICOAGULATION COMPARED TO HEPARIN DURING EXPANDED HEMODIALYSIS WITH THERANOVA® MEMBRANE
Authors: Vrečko Marija Malgaj , Pajek Jernej , Gubensek Jakob , Hudoklin Samo , Bozic-Mijovski Mojca , Osredkar Joško , Buturović-Ponikvar Jadranka 
Published: June 2023

Abstract

Background and Aims
Regional citrate anticoagulation (RCA) is known to improve the biocompatibility of hemodialysis (HD) by reducing complement, leukocyte and platelet activation. As continuous exposure to bio-incompatible HD may accelerate cardiovascular disease and increase mortality, improved biocompatibility may be important for clinical outcomes, including long-term survival of chronic HD patients. We found no reports of RCA during expanded hemodialysis (HDx), except our recent pilot study [1]. The aim of our trial was to compare RCA and full dose unfractionated heparin (UFH) during HDx with respect to biocompatibility parameters.

Methods
We performed a randomized, cross-over trial in 32 patients on chronic HD. Each had 2 HDx procedures with Theranova® membrane: one with UFH and one with RCA. RCA was achieved with 8% trisodium citrate at a flow rate of 150 mL/min. Anticoagulation with UFH was achieved by a bolus of 30 I.U. per kg of body weight, followed by an infusion of 18 I.U. per kg of body weight per hour. Anticoagulation was monitored by post-filter ionized calcium (RCA) or activated partial thromboplastin time (UFH). The primary outcomes were serum concentrations of C3a (marker of complement activation) and myeloperoxidase (MPO; marker of leukocyte activation) and plasma concentrations of platelet factor 4 (PF4; marker of platelet activation). Blood was drawn prior to, after 15 minutes and just before the end of HDx. The area under the biocompatibility marker concentration-time curve (AUC) was calculated for an individual biocompatibility marker from all three concentrations using the linear trapezoidal rule. As a secondary outcome, adhesion of blood cells and activation of clotting on inner surfaces of dialyzer fibers were visualized using scanning electron microscopy (SEM) in a subset of patients (n = 5). Biocompatibility parameters were compared between the groups using paired t-test or Wilcoxon signed-rank test.

Results
The trial included 22 males and 10 females. Patients were of mean age 65 ± 12 years with median dialysis vintage of 31 (IQR 17-89) months. Mean duration of HDx was 4.4 ± 0.4 hours (always the same for an individual patient). All patients had arteriovenous fistulas. Analysis of PF4 included only 8 patients, while the rest had concentrations of PF4 above the measuring range, probably due to unspecific platelet degranulation because of preanalytical factors. The concentrations of C3a, MPO and PF4 rose significantly after 15 minutes of HDx with UFH, while we observed no significant rises during HDx with RCA (Table 1). The AUC for biocompatibility markers were significantly smaller during HDx with RCA in comparison to UFH: 1163.0 ± 306.8 vs. 1444.1 ± 385.9 µgh/L for C3a (p&lt;0.001); 78.2 (IQR 39.0-131.2) vs. 275.1 (IQR 136.9-492.9) µgh/L for MPO (p&lt;0.001) and 100.0 (IQR 51.8-196.6) vs. 379.4 (IQR 295.0-553.0) IUh/mL for PF4 (p = 0.04). SEM showed almost no deposition on the membrane with comparable clotting score: 2 (IQR 1-3) for RCA vs. 2 (IQR 1-2.25) for UFH (p = 0.40).

Conclusion
Given the higher activation of complement, leukocytes and platelets during HDx with UFH, we conclude that RCA offers superior biocompatibility compared to UFH during HDx. Whether improved biocompatibility has clinical relevance remains to be explored.