Amino Acid Infusion Before Cardiac Surgery Reduced Acute Kidney Injury

An amino acid infusion reduced the occurrence of acute kidney injury (AKI) in adults undergoing elective cardiac surgery with cardiopulmonary bypass, the randomized PROTECTION trial showed.

Among over 3,500 patients, in-hospital AKI occurred in 26.9% of patients who received an intravenous infusion of a balanced mixture of amino acids compared with 31.7% of patients who received a placebo of Ringer’s solution (relative risk [RR] 0.85, 95% CI 0.77-0.94, P=0.002), reported Giovanni Landoni, MD, of IRCCS San Raffaele Scientific Institute in Milan, and colleagues.

Stage 3 AKI occurred in 1.6% and 3% of patients, respectively, representing a relative 44% reduction in risk (RR 0.56, 95% CI 0.35-0.87), according to results published in the New England Journal of Medicine.

“For the first time, we have an effective treatment to prevent acute kidney injury in our patients. This is the first time in medical history that this is happening,” said Landoni at the Critical Care Reviews meeting in Belfast, Ireland, where the study was simultaneously presented.

The researchers pointed out that the intervention “is straightforward and would be readily translated into practice,” adding that it works by boosting the estimated glomerular filtration rate (eGFR) by recruiting renal functional reserve, which may confer kidney protection.

“The combination of improved renal medullary perfusion and improved glomerular blood flow may be a key factor in conferring such kidney protection,” they wrote, explaining that “in patients undergoing cardiac surgery, renal functional reserve has been shown to be a crucial predictor of AKI and measure of kidney outcome, and a preoperative protein load has been associated with improved long-term renal outcomes.”

The double-blind trial included 3,511 patients from 22 centers across three countries. All were scheduled to undergo elective cardiac surgery requiring cardiopulmonary bypass and were expected to stay in the intensive care unit (ICU) for at least one night post-surgery. Some exclusion criteria included preoperative treatment or planned treatment with intermittent or continuous kidney-replacement therapy, and stage IV or greater chronic kidney disease defined as an eGFR under 30 mL/minute/1.73 m².

Participants randomized to the amino acid group received a continuous infusion of a balanced mixture of amino acids at a dose of 2 g/kg of ideal body weight per day (up to a maximum of 100 g per day) from the time of admission to the operating room to 72 hours after initiation of the infusion, discharge from the ICU, initiation of kidney-replacement therapy, or death — whichever occurred first.

Median patient age was 66-67, 30% were women, and 98% were white. Median preoperative serum creatinine level was 0.94-0.96 mg/dL, and 62% had arterial hypertension while receiving medical treatment. Surgeries were roughly equally split among coronary artery bypass grafting, mitral valve, and aortic valve surgeries.

The median dose of amino acids was 1,260 mL, corresponding to 126 g of amino acids. Median duration of infusion was 30 and 31 hours for the amino acid and placebo groups, respectively. The median infusion rate was 40 mL/hour in both groups. Most (72.1%) stopped receiving amino acids or placebo at ICU discharge, and 22.6% completed the maximum 72-hour infusion. Fourteen patients died before the end of the 3-day infusion.

Of the patients with AKI, most had stage 1: 430 patients in the amino acid group and 492 in the placebo group. According to the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria, stage 1 AKI is defined as an increase in the serum creatinine level of at least 0.3 mg/dL during a 48-hour period or a 50% increase from baseline during a 1-week period. Stage 2 AKI is defined as a doubling of the baseline serum creatinine level, and stage 3 AKI as a tripling of the baseline serum creatinine level or the initiation of dialysis, with either occurring within 1 week after surgery.

The use of kidney-replacement therapy — a secondary outcome of the trial — was not significantly different between the two groups: 1.4% in the amino acid group and 1.9% in the placebo group (RR 0.73, 95% CI 0.43-1.22).

Safety wasn’t an issue with treatment, as there were no significant differences between the two groups and no adverse drug reactions. The 30-day mortality rate was 2.8% in both groups, and 70 patients in the amino acid group and 62 patients in the placebo group underwent surgical revision for bleeding.

One limitation of the study was its reliance on serum creatinine level alone to diagnose AKI, since urinary catheters are typically removed within 48 to 72 hours after surgery.

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