Comparison of Biocompatibility and Efficacy of Regional Citrate Anticoagulation and Unfractionated Heparin During Expanded Hemodialysis With a Medium Cut‐Off Membrane—A Randomized Trial

ABSTRACT Background Regional citrate anticoagulation (RCA) improves the biocompatibility of hemodialysis (HD) by reducing activation of complement, leukocytes, and platelets. Despite the new possibility of expanded hemodialysis (HDx), RCA and unfractionated heparin (UFH) have not been compared in this dialysis modality. This study compared the biocompatibility and efficacy of RCA versus full‐dose UFH during HDx. Methods In a randomized cross‐over trial, 32 chronic HD patients each underwent two HDx sessions with a Theranova dialyzer: one with RCA and one with UFH. Biocompatibility was assessed by plasma complement factor 3a (C3a), myeloperoxidase (MPO), and platelet factor 4 (PF4) measured pre‐HDx, after 15 min, and at session end. In a subset of patients ( n = 5), scanning electron microscopy (SEM) visualized cell adhesion and clotting on dialyzer fibers. Efficacy outcomes were overall clearances and reduction ratios (RR) for creatinine, urea, and β2‐microglobulin. Results MPO and C3a increased after 15 min of HDx only with UFH ( p < 0.001). In the available PF4 data, a significant increase after 15 min of HDx occurred only with UFH ( p = 0.02). SEM showed minimal cell adhesion with both anticoagulants. Overall clearances and RRs of creatinine, urea, and β2‐microglobulin did not differ. RCA was well tolerated, with no significant electrolyte disturbances. Conclusions RCA during HDx provided superior biocompatibility over UFH, eliminating complement, granulocyte, and platelet activation without improving dialysis efficacy.