Hemodialysis Timing in Critically Ill Patients

Trial	Very Early	Early	Delayed/Standard	More-Delayed
ELAIN	x	x
AKIKI
IDEAL-ICU
STARRT-AKI		x	x
AKIKI 2			x	x

In summary: - early KRT may lead to more KRT dependence in the long term, and does not improve mortality - more-delayed KRT may increase mortality but does not decrease KRT dependence - Therefore, consider a delayed/standard approach for most patients:. Indications to proceed to dialyze in these circumstances are: - Stage II or III AKI + acidemia (pH < 7.20)/acidosis (bicarb < 12)/pulmonary edema (PF < 200)/72 hours of AKI (per STARRT-AKI) - Stage III AKI + oliguria/anuria or azotemia (Urea >40 mM) per AKIKI 2 - Consider a more-delayed approach for selected patients - Stage III AKI + preserved UOP + urea <40 mM (per AKIKI 2) - Dialyze emergently for urgent indications (severe metabolic acidosis, severe acidemia, severe volume overload) regardless of other patient characteristics

ELAIN (2016)

Question: In critically unwell patients with acute kidney injury, does early initiation of renal replacement therapy (RRT) compared to delayed initiation reduce all cause mortality at 90 days?

Single centre RCT in mostly surgical patients: lower mortality among patients that received KRT within 8 hours of developing AKI stage 2 + NGAL > 150 ng/ml vs patients that received KRT after 12 hours of developing AKI stage 3 or an absolute indication of KRT.

AKIKI (2016)

Question: In critically ill patients with acute kidney injury does delayed compared with early initiation of renal replacement therapy (RRT) reduce mortality at 60 days?

IDEAL-ICU (2018)

multicenter randomized trial showed no difference in mortality between septic patients that received KRT at 12 hours of developing AKI RIFLE stage F vs patients that received KRT after 48 hours of developing AKI RIFLE stage F.

STARRT-AKI (2020)

Early vs standard initiation of KRT. Multicentre multinational study of N=3000 patients.

Population

• Adults in the ICU with renal dysfunction and severe AKI (double Cr from baseline, or oliguria).
• Exclusion: emergency KRT indications, advanced baseline CKD, previous KRT

Arms

1. Accelerated strategy: KRT started within 12 hours
2. Standard strategy: KRT not started until one or more of hyperkalemia (K>6), acidemia (pH <7.20), metabolic acidosis (HCO3 <= 12), PF ratio < 200 and volume overloaded, or persistent AKI for 72 hours after randomization

Outcomes

1. Death from any cause at 90 days
2. Secondary outcomes: MAKE, pressors, VFDs, hospital LOS, etc.

Results

1. No significant difference in mortality at 90 days (44% vs 44%)
2. Increased RRT dependence at D90 with accelerated strategy (10.4% vs 6%, RR 1.74)
3. No sigificant difference in MAKE, eGFR D90, mortality in ICU or hospital, RRT free at D90, VFD at D90, pressor dependence at D90.

AKIKI 2 (2021)

Delayed vs more-delayed strategy.

Population

• adults in ICU on pressors or mechanical ventilation
• KDIGO Stage III AKI with oliguria/anuria or azotemia (Urea 40-50 mM)
• Excludes patients with urgent indications for RRT (hyperkalemia, acidosis, pulmonary edema despite diuresis, urea > 50 mM, baseline severe CKD

Arms

1. Delayed strategy (KRT to be initiated within 12 hours of fulfilling randomisation criteria)
2. More-delayed strategy (KRT postponed until an urgent indication occurred [see below] or urea > 50 mM for 1 day). Duration of anuria is not a criterion.

Outcomes

1. Primary outcome: KRT-free days up to day 28
2. Secondary outcomes included vital status up to 2 months, renal recovery at 60 days, CLABSIs

Results

1. Primary outcome: No significant difference between delayed strategy and more-delayed strategy (12 vs 10 days)
2. More-delayed strategy is associated with higher 60-day mortality in multivariate analysis (HR 1.65, p=0.018).
3. No difference in KRT dependence at day 60, AKI/RRT complciations, fluid balances, and other secondary outcomes