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February 11, 2018

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis.

Mazen Kherallah

Summarized by: 

What was the research question?

  • In septic shock patients with acute kidney injury not requiring emergent renal replacement therapy, does early initiation of RRT (within 12 hours) improve 90-day mortality compared to delayed initiation of RRT (after 48 hours)?

How did they do it?

  • A multicenter, randomized, controlled trial in 29 ICUs in France

  • 488 patients with early-stage septic shock and severe acute kidney injury at the failure stage of RIFLE classification (3-fold increase in creatinine, an increase of at least 0.5 mg/dL if baseline serum creatinine ≥4 mg/dL, a urine output ≤0.3 mL/kg/hr for ≥24 hours, or anuria ≥12 hours); and had no emergent need of renal replacement therapy (RRT) were randomized to receive early RRT within 12 hours (early strategy) or delayed RRT after 48 hours (delayed strategy).

  • The primary outcome was death at 90 days.

What did they find?

  • Among 477 out of 488 patients, 90-day mortality was not different in the early strategy compared to the late strategy (58% vs. 54%, P=0.38).

  • RRT was initiated in 97% of the early strategy compared to 62% in the delayed strategy (p<0.001, NNT 3).

  • Delayed strategy is associated with more RRT-free days compared to early strategy (12 vs. 16 days, P=0.006).

  • There were no differences between the two groups in relation to 28-day mortality, 180-day mortality, days free of mechanical ventilation, days free of  vasopressors, median length of stay in the intensive care unit or hospital stay, fluid balance, or RRT dependence among survivors.

Are there any limitations?

  • The trial was stopped early for futility after the second planned interim analysis prior to enrolling a planned 864 patients.

  • The study is underpowered and would have required 9669 patients per arm to show any significant difference.

What does it mean?

  • Among patients with septic shock and acute renal failure not requiring emergent renal replacement therapy, early initiation of RRT did not improve 90-day mortality compared to delayed strategy but it resulted in lower utilization of RRT.

  • The study impacted our ICU practice and now RRT is delayed unless there is an emergent need (i.e. hyperkalemia, acidosis, or pulmonary edema).


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