Intensive care unit continuous kidney replacement therapy: time to change dosage recommendations?

Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney support used for hemodynamically unstable adult ICU patients with severe AKI (KDIGO stage 3). The success of CKRT depends on the achieved doses. Practice patterns worldwide are highly variable. A contemporary understanding of treatment adequacy is essential. The KDIGO AKI clinical guidelines recommend delivering effluent volumes of 20-25 ml/kg/hour for CKRT in the ICU setting, with the caveat that higher prescribed doses (25-30 ml(kg/h) may be necessary to achieve adequate delivered CKRT doses. The reference landmark trials provide definitive evidence that increases of delivered CKRT doses beyond the recommended dose are not beneficial for unselected ICU patients with severe AKI. However, the minimum delivered CKRT intensity at which underdosing becomes harmful remains unknown. The answer to this question has clinical relevance (dosing of critically ill patients with obesity or Covid-19 disease, minimizing adverse effects of CKRT) and a relevant impact on the costs of CKRT. The delivered dose of CKRT for Japanese ICU patients with severe AKI has been generally smaller (median 15 ml/h/kg) than the recommended delivered KDIGO dose. The most recently published retrospective cohort study by Okamoto et al. demonstrated that low delivered CKRT doses were associated with a higher mortality among critically ill patients with severe AKI. These data challenge the nation-wide accepted hypothesis that a lower limit of delivered CKRT (< 20 ml/ kg/h) may adequately control uremia/volume overload. Thus, there is an unmet clinical need for prospective randomized trials defining the minimal effective dose of CKRT. Given the dynamic nature of the precipitating critical illness and the natural course of most episodes of AKI, CKRT dose targets are likely to vary. Doses should be tailored to the needs of the individual patient within the limits of the KDIGO guideline recommendations. The Japanese experience with low-dose CKRT is not practice changing.