The aim of this study is to evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.

Purpose of clinical trial:

To evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.

Patient population: critically ill patients with acute kidney injury requiring renal replacement therapy.

Primary objective:

Anticoagulation of the extracorporeal circuit is required in continuous RRT (CRRT). To this date, it is not clear which anticoagulant should be used for CRRT. Regional citrate anticoagulation (RCA) for CRRT in critically ill patients with AKI prolongs filter life span and reduces 90-day all cause mortality by approximately 8% (from 48% to 40%) compared to systemic heparin anticoagulation for CRRT

Inclusion Criteria:

1. Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability)

   Or

   Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation

2. At least one of the following conditions

   • Sepsis or septic shock
   • Use of catecholamines (norepinephrine or epinephrine ≥ 0.1 µg/kg/min or norepinephrine ≥ 0.05 µg/kg/min + dobutamine (any dose) or norepinephrine ≥ 0.05 µg/kg/min + vasopressin (any dose) or epinephrine ≥ 0.05 µg/kg/min + norepinephrine ≥ 0.05 µg/kg/min)
   • Refractory fluid overload: worsening pulmonary edema: PaO2/FiO2 < 300 mmHg and/or fluid balance > 10% of body weight)

3. 18-90 years old

4. Intention to provide full intensive care treatment for at least 3 days

5. Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation

Exclusion Criteria:

1. Patients with increased bleeding risk (e.g. an active bleeding from ulcers in the gastro-intestinal tract, hypertension with a diastolic blood pressure higher than 105 mm Hg, injuries (intracranial hemorrhage, aneurysm of brain arteries) of or surgical procedures on the central nervous system if a heparinization with a target aPTT 45-60 s is not allowed by the treating neurologist or neurosurgeon, severe retinopathies, bleeding into the vitreum, ophthalmic surgical procedures)) or injuries, active tuberculosis; infective endocarditis)
2. Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease)
3. Dialysis-dependent chronic kidney insufficiency
4. Need of therapeutic systemic anticoagulation
5. Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia
6. AKI caused by permanent occlusion or surgical lesion of the renal artery
7. AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction
8. Do-not-resuscitate order
9. Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
10. Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock
11. Kidney transplant within the last 12 months
12. Pregnancy and nursing period
13. Abortus imminens
14. No hemofiltration machine free for use at the moment of inclusion
15. Participation in another clinical intervention trial in the last 3 months
16. Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
17. Persons held in an institution by legal or official order