Association of duration of amino acids infusion and renal protection: a secondary analysis of the PROTECTION trial

Abstract

Background: Intravenous amino acids (AA) reduce acute kidney injury (AKI) in adult patients undergoing cardiac surgery. Because the optimal duration of AA infusion is unknown, we investigated the effect of AA infusion duration on AKI and survival. Methods: In a secondary post hoc analysis of the PROTECTION randomised double-blind placebo-controlled trial, we divided patients into brief (≤48 h) or prolonged (>48 h but ≤72 h) AA infusion. The primary objective was to assess whether the direction of the effects on AKI and ICU mortality was consistent across subgroups. Results: A total of 3481/3511 patients had available data. Brief and prolonged AA infusion had similar magnitude and direction of effect on AKI (interaction P=0.89), with a risk reduction of 3.8% (25% to 21%) and 5.7% (44% to 38%), respectively. Brief AA infusion showed a reduction in the use of renal replacement therapy, whereas prolonged infusion showed no effect. The effects of AA on intensive care unit mortality were discordant (a reduction from 1.9% to 1.0% in the brief infusion group, and an increase from 2.5% to 3.5% in the prolonged infusion group; interaction P=0.04). Conclusions: The effect of AA on AKI was consistent across subgroups, whereas they had opposing effects on survival in patients receiving brief or prolonged study drug infusion and in favour of the brief infusion group. Although these results are hypothesis generating, centres that are following European guidelines and PROTECTION trial results and are implementing AA in clinical practice should consider AA infusion lasting ≤48 h. Clinical trial registration: NCT03709264.