STARRT-AKI Enrollment Criteria

The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. STARRT-AKI is a study designed to determine whether early vs deferred initiation of renal replacement therapy offers clinical advantage.

Inclusion criteria include:

• Age >18 and admitted to ICU?
• Minimum creatinine of 130 µmol/L (1.47 mg/dL) for men and 100 µmol/L (1.13 mg/dL) for women
• At least one of the following:
  • Serum creatinine ≥ 354 µmol/L (4 mg/dL) + increase in creatinine ≥ 27 µmol/L (0.3 mg/dL) OR
  • ≥2-fold increase in serum creatinine from baseline OR
  • Urine output <6 ml/kg over preceding 12 hours
• Serum K ≤ 5.5 mmol/L AND bicarbonate ≥15 mmol/L

Exclusion criteria include:

• Drug overdose requiring renal replacement therapy (RRT)
• Lack of committment to life support
• Any RRT in the previous 2 months
• Kidney transplant in last 365 days
• Known pre-hospitalization CKD with eGFR < 20mL/min/1.73m²
• Presence/suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis

Provisionally eligible patients must be reviewed by the attending clinicians. If the attending clinicians reviews a provisionally eligible patient and agrees with either of the following, then the patient is excluded: i) Renal replacement therapy must be initiated immediately OR ii) RRT must be deferred, then the patient is excluded. Otherwise, the patient is fully eligible to enroll in STARRT- AKI. Patients excluded after clinician review can be reassessed if the clinician reconsiders and RRT has not yet been started.

Post-Randomization: RRT Initiation Procedure

RRT initiation procedure after randomization depends on the arm to which the patient has been randomized, as described below:

A) Accelerated RRT Initiation:

• Dialysis catheter should be placed and RRT should be initiated within 12 hours of eligibility; includes the time needed to obtain/document consent
• Provide reminders to the clinical team until RRT has been initiated

B) Standard RRT Initiation:

• RRT Initiation discouraged unless patient has persistent severe AKI as defined by sCr that remains >50% of the value recorded at randomization AND at least one of the following develops:
  • Serum potassium ≥6.0 mmol/L
  • pH ≤ 7.20 or serum bicarbonate ≤ 12 mmol/L
  • PaO2/FiO2 ≤ 200 and clinical perception of volume overload
  • Persistent severe AKI for > 72 hours from randomization

RRT may still be commenced at any time based on clinical judgment, however RRT initiation within 12 hours will be considered a protocol violation

Follow-up Procedures for Both Arms

• Both arms will receive identical daily follow-up from randomization until Day 14
• Each participant will be followed to 90 days from randomization
• Follow-up will conclude at 365 days from randomization

Guidance for RRT Prescription

IHD:

• Minimum session duration: 3 hours
• Minimum frequency: 3 per week
• Blood flow: 200-400 ml/min
• Dialysate flow: 500-800 ml/min
• Anticoagulation options: None/heparin/citrate

SLED:

• Minimum session duration: 8 hours
• Minimum frequency: 3 per week
• Blood flow: 200-300 ml/min
• Dialysate flow: 100-400 ml/min
• Anticoagulation options: None/heparin/citrate

CRRT:

• Minimum session duration: 24 hours
• Blood flow: 100-250 ml/min
• Total effluent: ≥20 mL/kg/hr
• Anticoagulation options: None/heparin/citrate