medwireNews: The continuous infusion of amino acids in adult patients undergoing elective cardiac surgery with cardiopulmonary bypass reduces the occurrence of acute kidney injury (AKI), without increasing adverse events, suggest findings from the PROTECTION trial.
In this multinational, double-blind trial, the relative risk for AKI within a week of cardiac surgery was reduced by a significant 15% among patients who received an infusion of amino acids for up to 72 hours compared with those who instead receiving crystalloid solution.
Giovanni Landoni (IRCCS San Raffaele Scientific Institute, Milan, Italy) and colleagues explain that a “short-term amino acid infusion increases [estimated glomerular filtration rate] by recruiting renal functional reserve and may confer kidney protection.”
They add: “The combination of improved renal medullary perfusion and improved glomerular blood flow may be a key factor in conferring such kidney protection.”
For the trial, conducted at 22 centers in three countries between 2019 and 2024, the 1759 patients who underwent cardiac surgery with cardiopulmonary bypass and were randomly assigned to receive amino acids were given a balanced mixture (isopuramin 10%), at a daily dose of 2 g/kg. The 1752 who were instead assigned to receive placebo were given Ringer’s solution at the same dose. The patients were aged a mean of 66 and 67 years, respectively, and 30.1% of patients in each group were women.
The primary outcome was incident AKI (stage 1 or above), defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Patients were diagnosed with stage 1 AKI if they had an increase in serum creatinine of at least 0.3 mg/dL (26.5 μmol/L) over 48 hours or a 50% rise from baseline within 7 days, with stage 2 if they had a doubling of their baseline serum creatinine level, and with stage 3 if their creatinine levels tripled or they needed dialysis within a week of surgery.
The median dose of amino acids administered was 126 g and the median duration of amino acid infusion was 30 hours, at a median rate of 40 mL/hour. In all, 22.6% of the patients completed the maximum 72-hour infusion.
As reported in The New England Journal of Medicine, the rate of any AKI at the time of hospital discharge was 26.9% in the patients receiving amino acids compared with 31.7% among those receiving placebo, a significant difference. Most of the patients with AKI had stage 1, at respective rates of 91.5% and 88.6%%, again a significant difference. The rate of grade 3 was halved with the use of amino acids, occurring in 1.6% of patients versus 3.0% of those receiving placebo.
Moreover, fewer patients in the amino acid group than the placebo group needed kidney replacement therapy, at 1.4% versus 1.9%, although the difference was not statistically significant.
For other secondary outcomes, such as median duration of kidney replacement therapy, mechanical ventilation, and hospital and intensive care stays, there were no significant differences between the two groups.
The two groups also did not differ significantly in terms of prespecified adverse events, including atrial fibrillation, need for noninvasive ventilation, and type 2 neurologic dysfunction, and need for surgical revision for bleeding. And the mortality rate at 30 days was the same with and without amino acid infusion, at 2.8%.
The investigators highlight that “the trial intervention is straightforward and would be readily translated into practice.”
They conclude that their findings are “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.”
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N Engl J Med; 2024; doi:10.1056/NEJMoa2403769