Background:　It　is　unclear　whether　different　modes　of　continuous　renal　replacement　therapy　(CRRT)　impact　post-filter　ionized　calcium　concentrations　during　regional　citrate　anticoagulation　(RCA)　when　using　calcium-containing　replacement　fluid.　Methods:　This　prospective,　single-center,　observational　cohort　study　will　screen　all　patients　receiving　CRRT　for　eligibility.　General　clinical　information　will　be　collected　before　commencing　CRRT　treatment.　Patients　will　be　randomly　assigned　to　either　the　continuous　veno-venous　hemofiltration　(CVVH)　or　continuous　veno-venous　hemodialysis　(CVVHD)　group　and　switch　to　the　alternative　mode　in　the　subsequent　treatment　session.　Pre-filter　and　post-filter　ionized　calcium,　systemic　total　and　ionized　calcium,　and　effluent　total　calcium　will　be　measured　2　h　after　the　initiation　of　CRRT.　Electrolyte　levels,　arterial　blood　gases,　hourly　citrate　dose,　and　total　citrate　dose　will　be　recorded　every　6　h　until　the　end　of　CRRT.　The　primary　outcome　is　the　difference　in　ionized　calcium　concentrations　at　each　site　over　time　between　the　two　modes.　Discussion:　This　study　will　build　upon　clinical　practice　to　explore　the　differential　effects　of　various　CRRT　modes　on　ionized　and　total　calcium　in　patients　undergoing　RCA-CRRT　with　calcium-containing　replacement　solutions.