Intravenous amino acid for kidney protection: current understanding and future perspectives

Acute kidney injury (AKI) is a common complication in critically ill and perioperative patients and is associated with mortality, morbidity, medical costs, and progression to chronic kidney function. Unfortunately, despite numerous research efforts, until recently, there was no AKI preventive therapy supported by level 1 evidence. Among the several factors that contribute to renal damage, two of the major triggers of AKI development are renal hypoperfusion and renal medullary hypoxia. The intravenous administration of a mixture of amino acids promotes the prevention of AKI through multiple mechanisms: the recruitment of renal functional reserve, increased renal blood flow, and improvements in renal oxygenation. Such mechanisms of action led to increased glomerular filtration rate and urine output in preclinical and pilot clinical studies. To test if these benefits on physiological parameters could be translated into clinically meaningful outcomes, a multicenter, randomized, placebo-controlled, trial was conducted in the cardiac surgery setting. Among 3511 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass, intravenous amino acid administration, compared to placebo, significantly reduced the occurrence of AKI, providing the first level 1 evidence of an effective treatment for AKI prevention. In this review, we provide the epidemiology and pathophysiology of cardiac surgery-associated AKI and the concept of renal functional reserve. Then, we summarize the underlying mechanisms of intravenous amino acid infusion as a renoprotective strategy and its preclinical and clinical evidence. Finally, we discuss the existing evidence gaps and future directions of this promising intervention.