Standard vs. Accelerated Initiation of RRT in Acute Kidney Injury (STARRT-AKI: Principal Trial)

Acute kidney injury (AKI) is a common and devastating complication of critical illness. Once
AKI is established, treatment is largely supportive and no intervention has been found to
restore kidney function or improve overall survival. Renal replacement therapy (RRT), usually
in the form of hemodialysis, is frequently needed to manage patients with severe AKI. Such
patients have an in-hospital mortality that consistently exceeds 50% with delays in RRT
initiation implicated as a possible contributor. A recent meta-analysis suggested that
earlier initiation of RRT may improve survival, but this is based on data derived
overwhelmingly from observational studies. The investigators recently completed a
multi-centre randomized controlled pilot trial that confirmed the feasibility of allocating
patients to two different strategies of RRT initiation. Patient recruitment and follow-up, as
well as patient safety, were successfully demonstrated during the pilot phase of this
research program. The optimal timing of RRT initiation is an existing knowledge gap and a
clear priority for investigation.

Inclusion Criteria:

1. Age ≥ 18 years

2. Admission to an intensive care unit (ICU)

3. Evidence of kidney dysfunction [serum creatinine ≥100 µmol/L (women) and ≥ 130 µmol/L
(men)]

4. Evidence of severe AKI defined by at least 1 of the following 3 criteria:

i) ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during
the current hospitalization; OR ii) Achievement of a serum creatinine ≥ 354 µmol/L
with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during
the current hospitalization; OR iii) Urine output < 6.0 mL/kg over the preceding 12
hours

Exclusion Criteria:

1. Serum potassium > 5.5 mmol/L

2. Serum bicarbonate < 15 mmol/L

3. Presence of a drug overdose that necessitates initiation of RRT

4. Lack of commitment to ongoing life support (including RRT)

5. Any RRT within the previous 2 months (either acute or chronic RRT)

6. Kidney transplant within the past 365 days

7. Known pre-hospitalization advanced chronic kidney disease, defined by an estimated
glomerular filtration rate < 20 mL/min/1.73 m2

8. Presence or clinical suspicion of renal obstruction, rapidly progressive
glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial
nephritis

9. Clinician(s) caring for patient believe(s) that immediate RRT is mandated

10. Clinician(s) caring for patient believe(s) that deferral of RRT initiation is mandated

- at their discretion, clinicians may administer a bolus of intravenous furosemide
(ie, "furosemide stress test") and evaluate the subsequent urine output to help
guide decision making regarding the likelihood of AKI progression