Please select the eligibility criteria that correspond to the clinical trial below.
Title: Regional Citrate Versus Systemic Heparin Anticoagulation for Super High-flux Continuous Hemodialysis in Septic Shock: Effect on Middle Molecular Weight Molecules Clearances
Brief Summary: Sepsis is responsible for 50% of all acute kidney injury (AKI) in intensive care units (ICUs), contributing greatly to multiple organ dysfunction syndrome (MODS). Special types of continuous renal replacement therapies (CRRT) have been proposed as adjuvant therapies for septic shock due to their ability to remove middle molecular weight molecules such as inflammatory mediators involved in MODS pathophysiology. These therapies are called extracorporeal " blood purification " therapies.

When CRRT is used, an anticoagulation is required to prevent clotting of the extracorporeal circuit, possibly causing bleeding in selected patients. Many anticoagulation strategies have been proposed and the most commonly used in 2013 is still unfractionated heparin. Regional citrate anticoagulation (RCA) is an interesting alternative as it dramatically decreases the bleeding risk.

The investigators hypothesize that the use of citrate with Super High Flux Continuous Veno-Venus Hemodialysis (SHF-CVVHD) would be highly beneficial over time by preserving the filter effectiveness via limiting protein adhesion (which subsequently reduces filter pore sizes (protein cake)), as compared to heparin. Consequently, higher clearances of the inflammatory mediators could be maintained over time with citrate as compared to heparin anticoagulation. In other words, for the same duration of filter use, middle molecular weight molecules and cytokines clearances would be greater with citrate as compared to heparin. To test this hypothesis, the investigators will perform a clinical randomized controlled trial which aim would be to compare middle molecular weight molecules and cytokines clearances in SHF-CVVHD using RCA versus systemic heparin anticoagulation in septic patients with AKI.


Options:
A: Inclusion Criteria:

* acute renal failure requiring renal replacement therapy

Exclusion Criteria:

* (recent) bleeding or a suspicion of bleeding necessitating transfusion,
* need of therapeutic anticoagulation or
* (suspected) heparin-induced thrombocytopenia
B: Inclusion Criteria:

1. The treating clinician believes that the patient requires CRRT for acute renal failure.
2. The clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with higher intensity or lower intensity CRRT.
3. The treating clinicians anticipate treating the patient with CRRT for at least 72 hours.
4. Informed consent has been obtained
5. The patient fulfils ONE of the following clinical criteria for initiating CRRT:

   * Oliguria (urine output \< 100ml/6hr) that has been unresponsive to fluid resuscitation measures.
   * Hyperkalemia (\[K+\] \> 6.5 mmol/L).
   * Severe acidemia (pH \< 7.2).
   * Urea \> 25 mmol/liter.
   * Creatinine \>300 micromol/L in the setting of ARF.
   * Clinically significant organ oedema in the setting of ARF (eg: lung).

Exclusion Criteria:

1. Patient age is \<18 years.
2. Death is imminent (\<24 hours).
3. There is a strong likelihood that the study treatment would not be continued in accordance with the study protocol.
4. The patient has been treated with CRRT or other dialysis previously during the same hospital admission.
5. The patient was on maintenance dialysis prior to the current hospitalisation.
6. The patient's body weight is \<60 kg or \>100kg.
7. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
C: 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
D: Inclusion Criteria:

* Male or female critically ill patients over the age of 18 years old
* Acute Kidney Injury requiring CRRT defined using the Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification with criterion I or worse.
* Septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.
* Written informed consent obtained from the patient or a patient's legal representative
* Patient patient's legal representative able to agree to patient's enrollment in the study with informed consent.

Exclusion Criteria:

* Pregnancy
* Participation in another research study protocol
* Known heparin induced thrombopenia or contraindication to heparin
* Pre-existing chronic renal failure on chronic dialysis
* Therapeutic anticoagulation with heparin for another reason (e.g. chonic arrhythmia)
* Severe liver failure (15% prothrombin time)

Answer: D