Timing of Renal Replacement Therapy and Patient Outcomes in the Randomized Evaluation of Normal Versus Augmented Level of Replacement Therapy Study

Objectives: To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury. The primary outcomes were all-cause mortality at 28 and 90 days. Design: Nested observational cohort study using data from the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study. Setting: Twenty-three ICUs in Australia and New Zealand. Patients: Four hundred thirty-nine critically ill patients with acute kidney injury Risk, Injury, Failure, Loss, End-stage kidney disease-injury (RIFLE-I) criteria. Interventions: None. Measurements and Main Results: The time between RIFLE-I acute kidney injury and randomization in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study (proxy for continuous renal replacement therapy commencement) was the variable of interest. All baseline variables in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study were assessed. Multivariable Cox, logistic, and linear regression models were used to assess the independent relationship of time of onset of RIFLE-I acute kidney injury and randomization and patient outcomes. The median time between RIFLE-I acute kidney injury and continuous renal replacement therapy commencement was 17.6 hours (interquartile range, 7.1-46 hr). Based on four groups of continuous renal replacement therapy commencement ([group 1; reference]: < 7.1, [group 2]: >= 7.1 to < 17.6, [group 3]: = 17.6 to < 46.0, [group 4]: = 46.0 hr), earlier commencement of continuous renal replacement therapy was not associated with a significantly lower risk of death at 28 days (hazard ratio for group 2: 1.06, 95% CI: 0.62-1.81; p = 0.83; hazard ratio for group 3: 1.23, 95% CI: 0.71-2.12; p = 0.46; hazard ratio for group 4: 1.33, 95% CI: 0.77-2.31; p = 0.31). Similar findings were observed for death at 90 days. Conclusions: In a subgroup of participants of the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study, earlier commencement of continuous renal replacement therapy relative to RIFLE-I acute kidney injury was not significantly associated with improved survival. Additional studies with larger sample sizes and broader commencement times are warranted.