No mortality difference between early and delayed renal replacement therapy: The AKIKI trial

1. Critically ill patients in the ICU with severe acute kidney injury (AKI) who were randomized to early renal replacement therapy (RRT) had essentially the same 60-day mortality rate as those whose treatment was delayed until a hard indication for renal replacement therapy arose.

2. Patients in the delayed-strategy group had significantly decreased rates of catheter-associated infections and were much less likely to undergo renal replacement therapy.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The optimal timing of RRT in critically ill patients is unknown. In the Artificial Kidney Initiation in Kidney Injury (AKIKI) trial, the investigators sought to shed light on this question with an open-label, prospective randomized trial. Patients were critically ill in the ICU (requiring mechanical ventilation, catecholamine infusion, or both) with severe AKI and were randomized to receive RRT in either an expedited or delayed manner. Those in the delayed group were started on RRT when they developed a life-threatening complication related to renal failure. At 60 days of follow-up, there was no significant difference in all-cause mortality between the two groups. There was a higher rate of catheter-related bloodstream infections in the early-strategy group, and approximately half of the patients in the delayed-strategy group did not require RRT.

This study provides a compelling design to answer a highly debated question in intensive care medicine. Its strengths are a randomized and prospective design that is more sophisticated than previous observational research, which had conflicting results and ran the risk of confounding. The drawbacks include generalizability, as the population only involved patients with severe acute kidney injury. Furthermore, while the results certainly point to benefits of a delayed-strategy approach (particularly in preventing unnecessary exposure to RRT in some patients), the protocolized monitoring required in this trial may be hard to replicate in real-world scenarios.

Click to read the study, published today in NEJM

Relevant Reading: Dialysis in Acute Kidney Injury — More is Not Better

In-Depth [randomized controlled study]: The AKIKI trial initially was an unblinded, prospective, multicenter, open-label two-group randomized trial conducted at 31 intensive care units in France. Patients were adults admitted to the ICU with KDIGO stage 3 AKI consistent with acute tubular necrosis and required mechanical ventilation or catecholamine infusion; they were randomized either to receive RRT within 3 hours of diagnosis or when they developed hyperkalemia, metabolic acidosis, pulmonary edema, BUN greater than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The specific methods of RRT were left to the discretion of the treating sites.

A total of 5528 patients were eligible but only 620 underwent randomization; the groups were well balanced, with 80% diagnosed with sepsis and 64% having recently received nephrotoxic agents. At 60 days, 61% of the patients who were alive in the delayed-strategy group had not received RRT. There was a Kaplan-Meier estimated overall mortality of 48.5 (95%CI 42.6 to 53.8) and 49.7% (95%CI 43.8 to 55.0) in the early and delayed-strategy groups respectively, which was a non-significant difference (p = 0.79). Length of stay in the ICU did not differ between groups. There was a significantly increased rate of catheter-related bloodstream infections in the early-strategy group (10% vs. 5%, p = 0.03).

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