Supplementary Appendix

Supplement to: Gaudry S, Palevsky PM, Dreyfuss D. Extracorporeal kidney-replacement therapy for acute kidney
injury. N Engl J Med 2022;386:964-75. DOI: 10.1056/NEJMra2104090

This appendix has been provided by the authors to give readers additional information about the work.
 TABLE OF CONTENTS OF SUPPLEMENTAL ELECTRONIC MATERIAL

1/ DEFINITION AND STAGING OF ACUTE KIDNEY INJURY (AKI)

• KDIGO
• RIFLE

2/ TABLE S1: COMPARISON OF THREE LARGE MULTICENTER RANDOMIZED

CONTROLLED TRIALS ON THE TIMING OF KRT IN ACUTE KIDNEY INJURY.

1
DEFINITION AND STAGING OF ACUTE KIDNEY INJURY (AKI)

KDIGO (2012)
STAGE 1 (definition of AKI)
Stage 1 is defined by at least one of the following criteria: increase in serum creatinine of
more than 0.3 mg/dl (26 µmol/liter) within 48 hours or greater than 1.5 times the baseline
creatinine level which is known or presumed to have occurred within the prior 7 days, urine
output below 0.5 ml/kg/h for more than 6 hours

STAGE 2
Stage 2 is defined by at least one of the following criteria: increase in serum creatinine
between 2 and 2.9 times the baseline creatinine level, urine output below 0.5 ml/kg/h for more
than 12 hours

STAGE 3
Stage 3 is defined by at least one of the following criteria: serum creatinine concentration of
more than 4 mg/dl (354 µmol/liter) or greater than 3 times the baseline creatinine level, anuria
(urine output of 100 ml/day or less) for more than 12 hours, oliguria (urine output below 0.3
ml/kg/h or below 500 ml/day) for more than 24 hours.

RIFLE (2004)
STAGE (RISK)
Stage R is defined by at least one of the following criteria: increase in serum creatinine of
greater than 1.5 times the baseline creatinine level, urine output below 0.5 ml/kg/h for more
than 6 hours.

STAGE (INJURY)
Stage I is defined by at least one of the following criteria: increase in serum creatinine of
greater than 2 times the baseline creatinine level, urine output below 0.5 ml/kg/h for more
than 12 hours.

STAGE F (FAILURE)

2
Stage F is defined by at least one of the following criteria: serum creatinine concentration of
more than 4 mg/dl (354 µmol/liter) or greater than 3 times the baseline creatinine level, anuria
(urine output of 100 ml/day or less) for more than 12 hours, oliguria (urine output below 0.3
ml/kg/h or below 500 ml/day) for more than 24 hours.

Comment: The severest stages of these classifications are of utmost importance as they were
used in trials on kidney replacement therapy timing as an indication for starting kidney
replacement therapy (KDIGO stage 3 in AKIKI, RIFLE F in IDEAL-ICU). Very similar stage
was used in STARRT-AKI trial.

3
 Table S1. Comparison of Three Large Multicenter Randomized Controlled Trials on the Timing of KRT in Acute Kidney Injury
Patients
Early KRT initiation criteria
Delayed KRT initiation criteria
Patients (n)
Time difference between delayed and
early KRT initiation (h)
Percentage of patients free of KRT in
the delayed group (%)
Survival (primary outcome)
Renal function recovery
ICU denotes intensive care unit, KDIGO Kidney Disease: Improving Global Outcomes, RIFLE risk, injury, failure, loss, and end-stage kidney disease classification, KRT
kidney replacement therapy
AKIKI
ICU patients receiving invasive
mechanical ventilation and/or
catecholamine infusion
KDIGO stage 3
• Serum potassium level of 6.0
mmol or more per liter
• Acute pulmonary edema due to
fluid overload responsible for
severe hypoxemia, despite
diuretic therapy
• Pure metabolic acidosis or
mixed acidosis with pH of 7.15
or less
• Blood urea nitrogen level higher
than 112 mg per deciliter
• Oliguria or anuria lasted for
more than 72 hours
619
52
49
Day 60 mortality
150/311 vs 153/308 (p=0.79)
• Earlier adequate diuresis
resumption in the delayed group
(P<0.001)
• KRT dependence at day 60:
2% in the early group and 5% in
the delayed; p = 0.12
IDEAL-ICU
ICU patients with early-stage septic
shock
FAILURE stage of RIFLE
• Serum potassium level of 6.5
mmol or more per liter
• Extravascular fluid overload
that was refractory, to
diuretics, with pulmonary
edema
• Metabolic acidosis with pH of
7.15 or less
• No renal function recovery
after 48 hours
488
44
38
Day 90 mortality
138/246 vs 128/242 (p=0.38)
• KRT dependence at day 28:
13% in the early group and
12% in the delayed; p = 0.89
STARRT-AKI
ICU patients
KDIGO stage 2 or 3
• Serum potassium level of 6.0 mmol
or more per liter
• Evidence of severe respiratory
failure and clinical perception of
volume overload
• pH of 7.20 or less or a serum
bicarbonate level of 12 mmol per
liter or less
• Persistent AKI for at least 72 hours
after randomization.
2927
25
38
Day 90 mortality
643/1465 vs 639/1462 (p=0.92)
• KRT dependence at day 90:
10 % in the early group and 6%
in the delayed; relative risk:
1.74; 95% CI, 1.24 to 2.43