Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Thus, a heparin-free easy-to-use alternative type of anticoagulation within the dialysis circuit is required. In a non-comparative study, heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance, was considered as safe and efficient. The aim of this study is to confirm the superiority of this approach compared to a anticoagulation based on heparin-grafted membrane.

Critically ill patients have a high risk of bleeding but also require prolonged intermittent dialysis. Several modalities are used for heparin-free dialysis sessions. Iterative saline infusion and heparin-grafted membranes are easy to use and remain the standards-of-care for high-risk bleeding situations but efficiency is low: success rates from hemodialysis sessions range from 50% to 65% and 50% to 75%, respectively. Furthermore, sessions that last for greater than 240 minutes are rarely achievable and can be problematic when ensuring an adequate dose of dialysis and a negative water balance in patients who cannot tolerate a high ultrafiltration rate. Thus, the development of alternative regional anticoagulation methods is needed urgently to improve intermittent hemodialysis (IHD) in critically ill patients and to avoid systemic anticoagulation in patients with a high risk of bleeding.

An easy way to provide citrate inside the filter, to lower iCa below 0.45 mmol/L could be to use diffusive influx from the dialysate. It has been demonstrated recently that the use of citric acid as the acidic component of dialysate can enable a dose reduction of heparin and increase the efficiency of hemodialysis. However, the amount of citrate (0.8 mmol/L) and calcium (1.25-1.75 mmol/L) contained in this dialysate do not allow the target of iCa to be reached in the ECC. In contrast, a citrate dialysate that contains no calcium would provide enough calcium-free transfer to lower iCa below 0.45 mmol/L; however, a problem would be the large amount of calcium loss during the session.

Pivotal studies show that, during dialysis sessions performed with calcium-free dialysate, the rate of calcium reinjection required to compensate for calcium loss in the dialysate can be easily deducted from the ionic dialysance (ID), which is an online measurement of instantaneous small solute clearance, available from most dialysis monitors. ID has been also used as a surrogate marker for dialysis dose in ICU patients receiving IHD. Thus, the use of calcium-free citrate-containing dialysate with calcium reinjection according to ID could provide enough citrate to prevent coagulation within the filter, and calcium restitution can then be monitored by online ID without the need for systemic measurement of iCa. It may also improve the hemodynamic tolerance of IHD by avoiding acetate in the dialysate.

The objective of the present study was to show the efficiency of this approach using RCA for dialysis sessions (<4 hrs) of IHD in patients with moderate to high risk of bleeding, based on the success rate of hemodialysis without clotting. Each patient included in this study will receive two heparin-free dialysis sessions with heparin-grafted membrane (control group) or RCA with calcium-free citrate-containing dialysate and calcium reinjection according to the ionic dialysance (experimental group), alternatively. The order of anticoagulation will be randomized.

Inclusion Criteria: will be included in the study, patients

• hat require two sessions of dialysis that last for greater than 240 minutes in the 7 days following the inclusion.
• With a moderate to high risk of bleeding (platelets count below 150.000/mm3; platelet disorders; bleeding in the last 10 days, surgery or biopsy in the last 10 days or planned in the next 7 days; admission to the ICU)
• Older than 18 years of age
• That gave written informed consent

Exclusion Criteria: will be excluded from the study, patients with

• Heparin allergy
• On-going treatment by vitamin-K antagonists (INR > 1.2) or unfractionated heparin (anti-Xa activity > 0.10)..
• Known allergy to the Evodial (Baxter, France) or Cordiax FX100 (Fresenius, France) membranes
• On-going treatment by angiotensin converting enzyme inhibitors
• Pregnancy or risk of pregnancy
• Patient under guardianship