"Renal-Replacement Therapy in Septic Shock with Acute Kidney Injury". The New England Journal of Medicine. ClinicalTrials.gov number, NCT01682590.

Clinical Question

In patients with early-stage septic shock and severe acute kidney injury (AKI) without life-threatening complications, does early initiation of renal-replacement therapy within 12 hours offer a mortality benefit over initiation after 48 hours?

Bottom Line

Early initiation of renal-replacement therapy in septic shock patients with severe AKI showed no significant difference in 90-day mortality compared to a strategy in which renal-replacement therapy was delayed for 48 hours.

Major Points

Guidelines

Design

Multicenter, randomized, controlled, open-label trial
N=488 patients with early-stage septic shock and severe AKI
Early initiation of renal-replacement therapy within 12 hours (n=239)
Delayed initiation after 48 hours without recovery (n=238)
Mean follow-up: 90 days
Primary outcome: All-cause mortality at 90 days

Population

Inclusion Criteria: Patients ≥18 years old within 48 hours of septic shock and vasopressor therapy onset, with severe AKI classified as "failure" stage by RIFLE criteria
Exclusion Criteria: Immediate need for emergency renal-replacement therapy before randomization
Baseline Characteristics: Comparable between both groups concerning demographics and clinical parameters

Interventions

Early strategy: Renal-replacement initiated within 12 hours after AKI documentation
Delayed strategy: Initiated after 48 hours delay if no spontaneous recovery and no emergency criteria developed

Outcomes

Primary Outcome: No significant difference in mortality at 90 days (early: 58%, delayed: 54%, P=0.38)
Secondary Outcomes: No significant differences in secondary outcomes, including 28-day and 180-day mortality, days free of renal-replacement therapy, and length of stay in ICU or hospital

Criticisms

- The adoption of the RIFLE classification which may not be as sensitive as KDIGO classification for identifying patients with AKI.
- A delayed strategy of only 48 hours may not be long enough to determine clear differences between early and delayed initiation of renal-replacement therapy.

Funding

The trial was funded by the French Ministry of Health.

Further Reading