During citrate-based Continuous Renal Replacement Therapy (CRRT), an infusion of calcium is necessary to replace the calcium lost in the effluent. The replacement takes place through a central venous catheter (CVC) that is primed with saline solution. Thus, we hypothesized a potential systemic anticoagulation caused by the unchelated citrate reaching the patient at the start of CRRT because of 0.42 ml of line dead space. In this pilot study, two subpopulations of 7 patients who underwent Continuous Veno-Venous Hemodiafiltration (150 ml/min of blood flow, 1500 ml/h dialysate flow, 1500 ml/h of citrate predilution) were studied. One had the CVC primed with saline, the second with calcium chloride 10%. Calcium replacement rate was 6.3 ± 0.2 ml/h. Ionized calcium concentration was studied over time in the two groups and in the group with saline priming we detected a transient period of hypocalcemia (ionized calcium concentration [iCa] < 1.00 mmol/l for the first 2 hours). In the subpopulation with the calcium priming, this was not present. No significant effect on filter life emerged. Priming of the catheter with calcium seems effective in avoiding a potential issue regarding citrate accumulation at the start of CRRT. More studies are needed to assess the clinical significance of this finding.