Intermittent hemodialysis as the initial treatment approach in patients with acute kidney injury (AKI) who were critically ill was not shown to be noninferior to continuous renal-replacement therapy with respect to major adverse kidney events by day 90, and it was associated with higher mortality, according to results from an open-label noninferiority trial published Oct. 14 in NEJM.

Stéphane Gaudry, MD, PhD, et al., randomly assigned critically ill adults with AKI who had indications for renal-replacement therapy to undergo intermittent hemodialysis or continuous renal-replacement therapy as the initial treatment across 38 intensive care units in France. Patients had a mean age of 64 years and 25% were women. Data were collected from October 2023 through July 2025.

The primary outcome was a major adverse kidney event by day 90, defined as death, dependence on renal-replacement therapy or a serum creatinine concentration >25% above the baseline value.

Importantly, this trial was stopped early after sequential interim analyses showed a sustained signal of higher mortality with intermittent hemodialysis.

Before trial termination, 554 patients underwent randomization; 260 in the intermittent group and 275 in the continuous group were included in the intention-to-treat population. The median duration of renal-replacement therapy was five days in the intermittent group and seven days in the continuous group.

The primary outcome occurred in 203 patients (78%) in the intermittent group and in 197 patients (72%) in the continuous group. Death by day 90 occurred in 164 patients (63%) and in 147 patients (54%), respectively. Kaplan-Meier mortality estimates at day 90 were 63% and 54% (hazard ratio, 1.30).

Notably, the most frequent complication potentially related to AKI or renal-replacement therapy was hypotension, which occurred in 69% of patients in the intermittent group and in 67% in the continuous group.

Gaudry and colleagues note that the higher mortality rate for intermittent hemodialysis was "...unexpected on the basis of data from previous literature," emphasizing that "...because the trial was stopped early, the magnitude of the mortality difference should be interpreted with caution."