Prof Giovanni Landoni, MD Associate Professor Università Vita-Salute San Raffaele Milan, Italy

NEJM: Perioperative Amino Acid Infusion Reduced Acute Kidney Injury after Cardiac Surgery Interview with:

Prof Giovanni Landoni, MDAssociate Professor
Università Vita-Salute San Raffaele
Milan, Italy

Prof. Landoni

Prof Giovanni Landoni, MD
Associate Professor
Università Vita-Salute San Raffaele
Milan, Italy What is the background for this study?

Response: Acute kidney injury (AKI) affects approximately 10-15% of hospitalized patients, and up to 50% of intensive care unit (ICU) patients.

In cardiac surgery one patient out of three will face AKI during the postoperative period, and this will lead to higher morbidity and mortality. AKI is associated with an elevated risk of chronic kidney disease, as well as, in the most severe cases, with the use of renal replacement therapy, which may double hospitalization costs, reduce quality of life, and increase long-term mortality. So far, no preventive measure with level I of evidence did exist for AKI.

The PROTECTION trial is a multinational, randomized, double-blind, placebo-controlled trial, conducted at 22 centers in 3 different countries. We recruited 3,511 adult patients undergoing cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of amino acids (AA) (Isopuramin 10%, Baxter), at 2g/kg/day up to a maximum 100g/day, or an equivalent dose of placebo (Ringer’s solution), for a maximum of 72 hours.

The primary outcome was the incidence of any stage of AKI, according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 creatinine criteria. What are the main findings?

Response:  Incidence of AKI was significantly lower in our treatment group (26.9%) when compared to placebo group (31.7%), with a relative risk reduction of 15% (relative risk, 0.85; 95% confidence interval, 0.77 to 0.94; p value=0.002). Moreover, stage 3 AKI occurred in 1.9% vs. 3.0% in AA and placebo group, respectively (relative risk 0.56; 95% confidence interval, 0.35 to 0.87). No adverse drug reactions and no substantial differences in secondary outcomes and adverse events were registered, thus proving that the intervention is safe. What should readers take away from your report?

Response: It is not easy to precisely define a single mechanism of action of AA, but rather several mechanisms contribute to kidney protection.  Previous studies have indeed demonstrated that AA stimulate the recruitment of renal functional reserve (RFR), increase renal blood flow, and enhance renal (both cortical and medullary) oxygenation, thus protecting kidneys from unavoidable insults.

The PROTECTION trial confirmed the efficacy of a perioperative AA infusion to prevent AKI after cardiac surgery. This is the first time that the effectiveness of a preventive therapy for AKI has been demonstrated in a multicentric randomized controlled trial, reaching the level I of evidence. What recommendations do you have for future research as a results of this study?

Response: Starting from now, we will be able to study and possibly apply these results also to several other clinical fields, thus potentially broadening the beneficial effect of amino acids.

Citation: New England Journal of Medicine
Landoni G, et al “A randomized trial of intravenous amino acids for kidney protection” N Engl J Med 2024; DOI: 10.1056/NEJMoa2403769.


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Last Updated on June 13, 2024 by Marie Benz MD FAAD