Amino Acid Infusion Reduces Risk of AKI in Cardiac Surgery Patients

Patients undergoing cardiac surgery commonly experience acute kidney injury (AKI), leading to an increased risk of morbidity and mortality, including chronic kidney disease, even in patients with mild or moderate AKI. Treatment for patients with severe AKI may include kidney replacement therapy (KRT). There is an association between severe AKI and doubling of hospitalization costs, decreased quality of life, and higher long-term mortality. 

According to Giovanni Landoni, MD, and colleagues, with the exception of implementation of supportive measures, there is no single protective intervention for AKI resulting from complications in patients undergoing cardiac surgery. The researchers reported results of the PROTECTION (Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery) trial online in the New England Journal of Medicine.

Infusion of intravenous acids in the context of renal hypoperfusion has been shown to provide renoprotective effects by recruiting renal functional reserve. The PROTECTION trial, a multinational, double-blind, randomized, placebo-controlled trial, included adult patients scheduled to undergo cardiac surgery with cardiopulmonary bypass. Researchers sought to test the hypothesis that intravenous amino acid therapy would result in a lower occurrence of postoperative AKI compared with placebo. 

The primary outcome of interest was the occurrence of AKI defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included AKI severity, the use and duration of KRT, and all-cause 30-day mortality. Patients scheduled to undergo cardiac surgery were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g per kilogram of ideal body weight per day) or placebo for up to 3 days. 

A total of 4415 patients were screened for eligibility from October 2019 through January 2024 at 22 centers in three countries. Of those, 3512 were enrolled in the trial. Prior to initiation of the trial regimen, one patient in the placebo group withdrew consent, resulting in a study population of 1759 patients in the amino acid group and 1752 patients in the placebo group. The two groups were similar in baseline demographic and clinical characteristics, surgical interventions, and management. 

The median dose of amino acids was 1260 ml, corresponding to 126 g of amino acids. Median duration of infusion was 30 hours in the amino acid group and 31 hours in the placebo group. In both groups, median infusion rate was 40 ml per hour. 

Overall, at discharge from the intensive care unit (ICU), 72.1% of the study population stopped receiving the amino acids or placebo (2530/3511); 22.6% (n=795) of patients completed the maximum 72-hour infusion. A total of 20 patients discontinued the regimen at initiation of KRT. In 1.6% (n=56) of patients, the regimen was discontinued in error. Fourteen patients died prior to the end of the 3-day infusion period, and one patient withdrew consent. Crossover occurred in four patients. 

As of time of hospital discharge, AKI had developed in 474 (26.9%) patients in the amino acid group and 555 (31.7%) in the placebo group (relative risk [RR], 0.85; 95% CI, 0.77-0.94; P=.002). Stage 1 AKI was the most common stage (430/474 in the amino acid group and 492/555 in the placebo group). Twenty-nine patients in the amino acid group and 52 in the placebo group developed stage 3 AKI. Results were similar in the per-protocol analysis, the as-treated analysis, and in all sensitivity analyses. 

KRT was used in 24 (1.4%) patients in the amino acid group and 33 (1.9%) in the placebo group (RR, 0.73; 95% CI, 0.43-1.22). Mean duration of KRT was 64 hours in both groups. Mean duration of stay in the ICU was 30 hours in the amino acid group and 34 hours in the placebo group. Mean duration of hospital stay was 7 days in both groups. 

In the amino acid group, mortality prior to discharge from the ICU occurred in 34 (1.9%) patients, compared with 38 (2.2%) in the placebo group. Thirty-day mortality occurred in 50 (2.8%) patients in the amino acid group and 49 (2.8%) in the placebo group. 

The two groups were similar in the numbers of patients with prespecified adverse events. Seventy patients in the amino acid group and 62 in the placebo group underwent surgical revision for bleeding. There were no adverse drug reactions reported in either group. 

The researchers cited some limitations to the study, including limiting diagnosis of AKI to serum creatinine level alone, lack of measurement of newly identified biomarkers of kidney injury, and lack of a strict protocol for management or prevention of AKI. Further, there were substantial differences between the trial population and patients in low- and middle-income countries and from patients in geographic regions with ethnic distributions that differed from the trial group. The lack of data on tubular injury and obtaining of serum creatinine measurements a few days prior to surgery were also cited as potential study limitations. 

In summary, the authors said, “In this trial involving adult patients scheduled to undergo elective cardiac surgery with cardiopulmonary bypass, the infusion of amino acids significantly decreased the overall occurrence of AKI.” 

Source: New England Journal of Medicine