1. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy.
2. Hazard ratio for mortality at day 60 was 1.65 in the more-delayed strategy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Uncertainty exists regarding the duration for which renal replacement therapy (RRT) can be postponed without inflicting harm to patients with severe acute kidney injury (AKI). While some studies show that delaying RRT in critically ill patients with no severe complications is safe, the extent to which this is true remains unclear. This randomized controlled trial aimed to assess whether a more-delayed initiation strategy (in which RRT is postponed until noticeable hyperkalemia, metabolic acidosis, pulmonary oedema, or blood urea nitrogen > 140 mg/dL) would result in more RRT-free days, compared with a delayed strategy (in which RRT is initiated after randomization). The primary outcome was number of RRT-free days between randomization to day 28, while key secondary outcomes included vital status at day 28 and 60, the percentage of patients receiving RRT at least once, and the number of RRT sessions between randomization and day 28. According to results, the primary outcome of RRT-free days was greater in the delayed strategy compared to the more-delayed strategy. This study was limited by the definition of “delayed” and “more-delayed” treatment with investigators using arbitrary clinical parameters to initiate RRT. Furthermore, the study does not allow for a longitudinal follow-up of patients to assess their quality-of-life with respect to both groups. Nonetheless, this trial provides valuable insight about the limit to which RRT can be safely postponed in critically ill patients with severe AKI.
Relevant Reading: Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury
In-depth [randomized controlled trial]: Between May 7, 2018, and Oct 11, 2019, 5336 patients were assessed for eligibility from 39 intensive care units in France. Included patients were ≥ 18 years old and hospitalized in the ICU with acute kidney injury (monitored until they had oliguria for > 72 h or a blood urea nitrogen concentration > 112 mg/dL). Those with immediate RRT indication, severe chronic renal failure, recent cardiac arrest, and ongoing pregnancy were excluded. Altogether, 278 patients (137 in the delayed strategy and 141 in the more-delayed strategy) were included in the intention-to-treat (ITT) population.
The primary outcome of RRT-free days did not differ between the delayed strategy (12 days, interquartile range [IQR] 0-25) and the more-delayed strategy (10 days, IQR 0-24, p=0.93). This was also true for 60-day mortality in both groups (44% of patients in the delayed strategy group died versus 55% in the more-delayed strategy group, p=0.071). However, in a multivariable analysis, the hazard ratio for death and mechanical ventilation at 60 days was significantly higher in the more-delayed strategy group (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.09-2.50, p=0.018 and HR 3.44, 95% CI 1.52-7.81, p=0.0020, respectively). Secondary outcomes concerning RRT dependence at day 60 and complications related to AKI or RRT were similar between both groups. Overall, findings from this study suggest that in severe AKI patients with oliguria > 72 h or blood urea nitrogen concentration > 112 mg/dL, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.
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