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PURPOSE To evaluate the feasibility of a protocol-based algorithm to wean acute kidney injury (AKI) patients from continuous renal replacement therapy (CRRT). METHODS The protocol was introduced on one of two similarly equipped ICUs, while on the other (reference) ICU, CRRT discontinuation was based on clinical judgement. Patients were allocated to either ICU and were subjected to physician- or protocol-directed weaning, respectively. According to the algorithm, periodical withdrawal trials (WTs) were mandatory. Interventions were recommended (administration of diuretics, fluid, vasopressors, inotropes, or human albumin) to achieve specific goals (sufficient urine output, balanced fluid status, adequate renal perfusion pressure, optimal oxygen delivery, normoalbuminemia). Clearly stated criteria defined when to abort a WT and to resume RRT for one cycle, followed by another WT. RESULTS Urine output and ScvO2 during WTs were higher with protocol-directed weaning, as well as the amount of administered fluids. WT abort ratio was 48% with a tendency to prolonged WT duration, compared to 64% in the reference patients. No relevant adverse side effects were observed. CONCLUSION Our data show the feasibility of a structured approach to wean AKI patients from RRT that bundles established interventions and brings the weaning into the physician's focus.