Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-associated Acute Kidney Injury in the Intensive Care Unit
Brief Summary: Sepsis continues to be a major global cause of both mortality and morbidity. Furthermore, the development of acute kidney injury (AKI) in sepsis increases the risk of unfavorable outcomes. Besides source control, fluid resuscitation and the use of antibiotics, application of extracorporeal renal replacement therapies (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, the timing of initiation of RRT remains controversial. It is reported that a correlation was observed between the concentrations of circulating inflammatory cytokines and mortality in patients with septic shock. Therefore, it is hypothesis that adequate removal of inflammatory mediators from the circulation may provide a potential therapy for this devastating condition. Indeed, data from meta-analyses, observational studies and randomized controlled trial (RCT) suggests that initiating RRT in critical ill patients (including patients with sepsis and non-sepsis) at early stage may be beneficial. But in some studies, initiating RRT at early stage do not shown to improve survival compared with initiating RRT at late stage. At present, large-scale prospective RCT about the timing for initiating RRT in SAKI was still lack.The decision when to start RRT is not merely academic but may impact on outcomes. Therefore, in our study, 460 patients with SAKI at KDIGO 2 from multicenter in China will be recruited. And then the patients will be divided into early group and delayed group randomly. In the early group, continuous RRT (CRRT) was started immediately after randomization. In the delay group, CRRT was initiated if at least one of the following criteria was met: KDIGO 3, severe hyperkalemia, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter after randomization. Overall survival at day 90 will be observed in order to understand whether different CRRT strategy would affect the outcomes of SAKI. This clinical study will be a large-scale, multi center, prospective, randomized trial about SAKI. It will help clinician choose appropriate timing to initiate CRRT and improve outcomes of SAKI.


Options:
A: Inclusion Criteria:

* Age older than 18 years old and admission in an ICU
* Acute kidney injury (defined by serum creatinine increase ≥ 0.3 mg/dL or urine output ≤ 0.5 mL/kg/hour according to KDIGO criteria)
* Informed consent provided by the patient or person with decisional responsibility
* Indwelling bladder catheter
* Documented cause of acute kidney injury from acute tubular necrosis e.g. presence of granular or epithelial casts on urine sediment, FeNa more than 1%, Feurea more than 50%, urine or plasma neutrophil gelatinase-associated lipocalin (NGAL) more than 150 mg/dL
* Opinion of the treating clinical team that patient was well resuscitated and sufficiently clinically stable for the intervention or by noninvasive or invasive measurements i.e. fluid accumulation at least 5% plus at least one of the following e.g. chest radiography, central venous pressure ≥ 8 mmHg, pulse pressure variation \< 13%, inferior vena cava collapsibility index \< 50% in spontaneously breathing patients or distensibility index \< 18% in mechanically ventilated patients

Exclusion Criteria:

* Baseline serum creatinine ≥ 2 mg/dL (male) and ≥ 1.5 mg/dL (female) within 3 months
* Evidence of volume depletion at the time of furosemide administration or active bleeding
* Evidence of obstructive uropathy, renal vein thrombosis or renal artery stenosis, thrombotic microangiopathy, glomerulonephritis, tumor lysis syndrome
* History of renal allograft
* Known pregnancy
* Allergy or known sensitivity to loop diuretics
* Need for emergency renal replacement therapy at randomization or evaluation by the clinical team that the renal replacement therapy should be deferred
* Patient is moribund with expected death within 24 hr or whom survival to 28 days is unlikely due to an uncontrollable comorbidity (cardiac, pulmonary or hepatic end-stage disease; hepatorenal syndrome; poorly controlled cancer; severe post-anoxic encephalopathy; etc.)
* Patients with advance directives issued expressing the desire not to be resuscitated
* Prior treatment with RRT within 30 days
B: Inclusion Criteria:

1. Adult patients (over 16 years of age) admitted to a participating ICU
2. Serum creatinine increase of ≥ 50% from baseline
3. Hemodynamic instability as defined by the cardiovascular component of the SOFA score of ≥ 1
4. Attending physician deems the patient a candidate for RRT for at least one of the following reasons:

   1. Presence of oliguria, defined as a urine output of \< 100 mL in the preceding 4 hours
   2. metabolic acidosis (HCO3- \< 15 mmol/L and pH \< 7.25)
   3. refractory hyperkalemia (K \> 6.0 mmol/L)
   4. azotemia (BUN \> 50 mmol/L)
   5. suspected uremic organ involvement (pericarditis, encephalopathy, neuropathy or myopathy)

Exclusion Criteria:

1. renal replacement therapy within the previous 2 months
2. presence of renal obstruction
3. receipt of a kidney transplant in the previous year
4. diagnosis of rapidly progressive glomerulonephritis, vasculitis, or acute interstitial nephritis
5. indication for intermittent hemodialysis, specifically severe hyperkalemia, dialyzable drug or toxin
6. terminal illness with associated life expectancy less than 2 months
7. patients who are moribund
8. prior enrollment in this study
9. enrollment in a competing ICU interventional study
10. no CRRT machine available
11. acute renal replacement ongoing for \> 36 hours
C: Inclusion Criteria:

* Acute renal failure clinically consistent with a diagnosis of acute tubular necrosis
* Plan for renal replacement therapy by clinical team
* Receiving care in a critical care unit
* One non-renal organ failure or sepsis
* Age 18 or older
* Patient or surrogate provides informed consent

Exclusion Criteria:

* Baseline serum creatinine \> 2 mg/dL (177 mol/L) in males, \> 1.5 mg/dL (133 mol/L) in females
* Acute renal failure clinically believed to be due to an etiology other than acute tubular necrosis
* More than 72 hours since meeting both of the following conditions:

  1. Fulfillment of the definition of ARF; and
  2. BUN \> 100 mg/dL (36 mmol/L)
* More than 1 hemodialysis treatment or more than 24 hours since starting continuous renal replacement therapy
* Prior kidney transplant
* Pregnancy
* Prisoner
* Weight \> 128.5 kg
* Non-candidacy for renal replacement therapy
* Moribund state
* Patient not expected to survive 28 days because of underlying terminal chronic medical condition
* Comfort-measures-only status
* Participation in a concurrent interventional study
* Patient/surrogate refusal
* Physician refusal
D: Inclusion criteria

1. Age between 18 and 90 years.
2. Patients admitted into ICU with Sepsis (sepsis-3) compatible with the diagnosis of AKI at stage 2 of KDIGO classification.
3. Informed consent provided by the patient or person with decisional responsibility.

Exclusion criteria

1. Presence of one of the emergent CRRT conditions before randomization:

1. Hyperkalemia \> 6.0 mmol/L or \> 5.5 mmol/L persisting despite medical treatment.
2. Acute pulmonary edema due to fluid overload responsible for severe hypoxemia requiring oxygen flow rate \> 5 L/min to maintain a percutaneous oxygen saturation (SpO2) \> 95% or a fraction of inspiration oxygen (FiO2) \> 50% in patients already on invasive or non-invasive mechanical ventilation and despite diuretic therapy.
3. Blood urea nitrogen (BUN) \> 112 mg/dl (40 mmol/L). 2. Pre-existing severe chronic renal failure \[estimated glomerular filtration rate (eGFR) \< 30 ml/min\].

3. Previous renal replacement therapy. 4. Prior kidney t

Answer: D