ICRAKI Trial Halts Early After Intermittent Hemodialysis Shows Higher Mortality in Acute Kidney Injury
When evaluated against continuous renal-replacement therapy for critically ill patients suffering from acute kidney injury, intermittent hemodialysis was not shown to be noninferior, leading to an increased rate of death within an open-label study that was terminated prematurely by its data and safety monitoring board. Findings from the randomized ICRAKI trial showed that a major adverse kidney event by day 90 occurred in 78.1% of patients assigned to intermittent hemodialysis, compared with 71.6% of those assigned to continuous therapy.
The multicenter trial enrolled 554 participants across intensive care units in France between October 2023 and July 2025, falling short of its original enrollment goal of 1,000 patients. Stéphane Gaudry, MD, PhD, of Avicenne Hospital in Bobigny, France, and his research colleagues tracked patients in an intention-to-treat analysis of 535 individuals. Most study participants were admitted to the ICU for medical reasons rather than surgical ones, with roughly half experiencing acute respiratory distress syndrome at baseline and over 70% receiving invasive mechanical ventilation upon admission.
Mortality Rates and Patient Outcomes by Day 90
By day 90 of the trial, deaths occurred in 63.1% of the intermittent hemodialysis arm compared with 53.5% of the continuous therapy arm. Kaplan-Meier mortality estimates suggested a 30% higher risk of death associated with the intermittent approach, yielding a hazard ratio of 1.30 with a 95% confidence interval ranging from 1.04 to 1.63. According to Gaudry and his colleagues, the decision to halt the trial early was defensible on ethical grounds, yet this action could have diminished the accuracy of treatment-effect calculations and inflated the perceived effect on mortality.
Common coexisting conditions among the patient cohort included hypertension in 50%, type 2 diabetes in 28%, chronic kidney disease in 19%, and congestive heart failure in 11%. Researchers described the higher mortality signal in the intermittent hemodialysis group as unexpected based on prior literature and not readily explained. Post hoc analyses pointed toward greater hemodynamic stress during intermittent treatments, though study authors emphasized that these exploratory findings only generate hypotheses and do not establish a causal mechanism.
Clinical Trade-offs and Prior Trial Comparisons
In an accompanying editorial, Paul Palevsky, MD, of the Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, detailed the distinct physiological trade-offs of each modality. Intermittent hemodialysis removes toxins rapidly and corrects fluid and electrolyte imbalances quickly, allowing a single machine to treat multiple patients successively. However, those rapid fluid and electrolyte shifts can contribute to hemodynamic instability.
Conversely, continuous renal-replacement therapy offers slower volume removal and lower solute clearance, theoretically causing less hemodynamic stress. Palevsky noted that earlier small-to-moderately sized trials largely showed no difference in survival between the two methods. Gaudry and co-authors suggested that earlier studies were conducted before trial-proven criteria for initiating renal-replacement therapy were established, whereas ICRAKI enrolled only patients with documented clinical indications, shifting the target population.
Treatment Duration and Post-Day-Three Switching Patterns
Assigned therapies in the trial were maintained for at least 4 consecutive days unless a patient experienced kidney recovery. The median duration of renal-replacement therapy reached 5 days in the intermittent group and 7 days in the continuous group. Thereafter, clinicians were permitted to switch treatment modalities based on usual clinical practice.
Treatment switching occurred in 21.9% of patients in the intermittent group and 42.5% of patients in the continuous group. Because of this flexibility, the trial does not establish which method is preferable for treatment after the first 3 days, when risk-benefit trade-offs may shift. Hypotension emerged as the most common complication in both arms, affecting 68.8% of patients receiving intermittent therapy and 66.5% of those receiving continuous therapy.
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