A randomized trial of intravenous amino acids for kidney protection

BACKGROUND Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer’s solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS The authors’ full names, academic de- grees, and affiliations are listed in the Ap- pendix. Dr. Landoni can be contacted at landoni.giovanni@hsr.it or at the Depart- ment of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. *The members of the PROTECTION study group are listed in the Supplementary Appendix, available at NEJM.org. This article was published on June 12, 2024, at NEJM.org. N Engl J Med 2024;391:687-98. DOI: 10.1056/NEJMoa2403769 Copyright © 2024 Massachusetts Medical Society. CME We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P=0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other sec- ondary outcomes or in adverse events. CONCLUSIONS Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.)