AKI
Aiya Almogaber, PharmD
Research shows that an infusion of amino acids may help protect patients from acute kidney injury (AKI) following cardiac surgery. The findings, published in NEJM on June 12, 2024, indicate that patients who received the infusion experienced fewer cases of AKI, a common complication that can lead to poor outcomes, including increased mortality and a higher risk of chronic kidney disease.
The PROTECTION trial involved 3,511 patients with a baseline eGFR of at least 30 mL/min/1.73 m2. Researchers evaluated the effects of an amino acid infusion on kidney function after cardiac surgery. Patients were randomly assigned to receive either an amino acid infusion (Isopuramin 10%–Baxter) or placebo (Ringer’s solution–Baxter). The infusion started before surgery and continued for up to 72 hours.
According to the findings, AKI of any stage occurred in significantly fewer patients in the amino acid group than in the placebo group, and the incidence of severe stage 3 AKI was also lower.
Previous studies have suggested that amino acid infusions improve kidney perfusion during cardiac surgery, reducing the risk of AKI. The PROTECTION trial supports these findings, showing a lower AKI rate in the amino acid group compared to placebo. However, similar to past research, the trial leaves questions about whether this reduction indicates true kidney protection or merely functional improvement. The lack of data on biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) highlight the need for further research to explore long-term effects and clarify the mechanisms behind the observed benefits.
Key findings
The research highlights the potential of amino acid infusions in reducing the risk of AKI after cardiac surgery. Although the overall incidence of AKI was lower in the amino acid group, the reduction in stage 3 AKI was particularly notable. The trial was double-blind and included patients from 22 centers in three countries, ensuring a high level of generalizability and robust data collection.
However, several aspects of the trial design complicate the findings. In particular, 336 patients underwent hemofiltration during cardiac surgery, which affected the researchers’ ability to assess postoperative creatinine levels accurately.
Additionally, the trial did not include data on biomarkers for tubular injury, such as NGAL or KIM-1. These biomarkers are essential in determining whether the AKI observed was functional or due to true kidney damage. Without these data, it remains unclear whether the reduction in AKI represents protection from tubular injury or simply a functional improvement in kidney filtration.
Study limitations
The PROTECTION trial faced a few limitations. In 104 patients, the trial infusion was stopped prematurely, which may have introduced bias against the intervention. Despite this, the per-protocol analysis did not show a significant difference in stage 2 or stage 3 AKI between the two groups.
Additionally, the study did not turn out long-term data, such as the development of chronic kidney disease in patients beyond 90 days after surgery. Similarly, health outcomes such as mortality rates at 30, 90, and 180 days, as well as the need for kidney-replacement therapy, showed no significant differences between the groups.
Questions remain
The PROTECTION trial offers important insights into the potential role of amino acid infusions in reducing the risk of AKI following cardiac surgery.
Although questions remain about whether the observed reduction in AKI is due to functional improvement or protection against tubular injury, the study’s results are promising.
Further research is needed to explore long-term outcomes, such as the progression of chronic kidney disease and quality of life after surgery. ■