Alternative net ultrafiltration rate strategies in acute kidney injury: a feasibility randomized clinical trial

Observational studies link high net ultrafiltration (UFNET) rates during continuous kidney replacement therapy (CKRT) to increased mortality. The Restrictive versus Liberal Rate of Extracorporeal Volume Evaluation in Acute Kidney Injury trial evaluated the feasibility of a restrictive versus liberal UFNET rate strategy. This stepped-wedge cluster-randomized trial enrolled patients in ten ICUs across two healthcare systems from July 2022 to June 2024. Each ICU was a cluster, with 1 randomly transitioning from liberal (2.0-5.0 mL/kg/h) to restrictive (0.5-1.5 mL/kg/h) group every two months after the first six months. The coprimary outcomes included between-group separation in UFNET rates, protocol adherence, and recruitment rate. Of 97 patients (55 liberal, 42 restrictive) enrolled, the mean (SD) delivered UFNET rate did not differ between the groups (2.05 [0.83] vs. 1.81 [0.86] mL/kg/h; adjusted P = 0.4). In per-protocol analysis, there was a significant between-group separation in mean UFNET rates (2.24 [0.72] vs. 1.22 [0.32] mL/kg/h; P = 0.002). Protocol deviations were similar (9.1% vs.7.1%, P = 0.7), and the recruitment rate was 0.99 (0.27) patients per ICU per two months. The use of rescue UFNET was higher in the restrictive group (14.5% vs. 66.7%; P < 0.001). In conclusion, despite high protocol adherence, there was minimal separation in delivered UFNET rates. While both strategies were feasible in select patients, the high rates of hemodynamic instability, the need for rescue UFNET, and physician override orders suggest that UFNET is more often driven by dynamic patient physiology than fixed protocols. This makes it challenging to maintain distinct, alternative UFNET targets in clinical practice.Trial registration number: ClinicalTrials.gov Identifier: NCT05306964.