Study Shows Infusion of Amino Acids Reduces Risk of Acute Kidney Injury Following Cardiac Surgery

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Findings from a Phase III trial (NCT03709264) show that intravenous (IV) infusion of amino acids in adults undergoing cardiac surgery lowers the risk of acute kidney injury (AKI).^1,2 The authors of the study, published by The New England Journal of Medicine, noted that amino acids have been found to increase kidney perfusion and enlist renal functional reserve, but their efficacy in decreasing the occurrence of AKI following cardiac surgery remains unclear.

“Even mild or moderate AKI is independently associated with increased morbidity and mortality, including an increased risk of chronic kidney disease,” the study authors wrote. “In patients with severe AKI, kidney-replacement therapy is common and is associated with doubling of hospitalization costs, decreased quality of life, and higher long-term mortality. However, other than the implementation of supportive measures, there is no single preventive intervention for cardiac surgery–associated AKI.”¹

The authors added that prior research indicates infusing amino acids elevates nephron plasma flow by reducing afferent arteriolar resistance, lowering tubuloglomerular feedback activation, and increasing cortical nitric oxide synthase activity.

“Moreover, in studies in animals, amino acid infusion increased renal perfusion, renal oxygenation, and GFR,” the study authors wrote. “Finally, pilot studies in humans have shown evidence that amino acid infusion is safe and has beneficial short-term and long-term effects on kidney function after cardiac surgery, as well as potential survival benefits in critical illness in general.”¹

The multinational, double-blind, randomized trial enrolled adults scheduled to undergo cardiac surgery with cardiopulmonary bypass. Patients received IV infusion of a balanced mix of amino acids (2 g per kilogram of ideal body weight per day) or a placebo for up to three days. The trial’s primary outcome was occurrence of AKI as defined by Kidney Disease: Improving Global Outcomes creatinine criteria, with secondary outcomes that included severity of AKI, use and duration of kidney-replacement therapy, and all-cause 30-day mortality.

Inclusion criteria included being 18 years of age and older with a scheduled elective cardiac surgery requiring cardiopulmonary bypass, and patients were expected to stay in the intensive care unit for at least one night following the procedure. Patients were also required to have a baseline serum creatinine measurement prior to the procedure.

A total of 3511 patients were included from 22 centers in three countries. Investigators randomly assigned 1759 patients to the amino acid cohort and 1752 patients to the placebo cohort. AKI was observed in 474 patients (26.9%) in the amino acid cohort compared to 555 (31.7%) patients in the placebo cohort (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P=0.002).

Stage 3 AKI was observed in 29 patients (1.6%) in the amino acid cohort compared to 52 patients (3.0%) in the placebo cohort (relative risk, 0.56; 95% CI, 0.35 to 0.87). Further, kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid cohort compared to 33 patients (1.9%) in the placebo cohort. In terms of safety, investigators did not observe any substantial differences between either cohort in other secondary outcomes or adverse events.

“The infusion of amino acids appeared to be safe and effective for the prevention of AKI in patients undergoing cardiac surgery,” the study authors wrote. “Moreover, the lower percentage of patients with stage 3 AKI in the amino acid group than in the placebo group implied an effect on AKI severity. These findings appear to be clinically and epidemiologically important because they may apply to more than two million patients who undergo heart surgery worldwide every year and because AKI is an independent risk factor for subsequent chronic kidney disease.”¹

References

1. Landoni G, et al. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Engl J Med 2024;391:687-698. DOI: 10.1056/NEJMoa2403769. Vol. 391 No. 8.

2. Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery. (PROTection). ClinicalTrials.gov ID. April 5, 2024. https://clinicaltrials.gov/study/NCT03709264