Metabolic Conditioning for Renal Protection During Cardiopulmonary Bypass: A Narrative Review

ABSTRACT Background Acute kidney injury (AKI) remains one of the most frequent and prognostically relevant complications following cardiac surgery, even in the era of modern cardiopulmonary bypass (CPB) management and goal‐directed perfusion. Cardiac surgery–associated AKI (CSA‐AKI) is associated with increased postoperative morbidity, prolonged hospitalization, neurocognitive complications, and reduced early as well as long‐term survival. Although optimization of macrocirculatory parameters and oxygen delivery has demonstrated benefits, renal injury often occurs despite apparently adequate perfusion and oxygenation. Recent evidence suggests that CPB‐related metabolic stress and protein catabolism contribute to renal vulnerability. Indeed, intravenous amino acid administration has emerged as a novel metabolic strategy for renal protection. Materials and Methods This narrative review was informed by a structured literature search of PubMed/MEDLINE, Embase, and the Cochrane Library, covering publications from database inception through March 2025. Search terms included combinations of “acute kidney injury,” “cardiac surgery,” “cardiopulmonary bypass,” “amino acids,” “intravenous amino acid infusion,” “renal protection,” and “goal‐directed perfusion”. Randomized controlled trials, meta‐analyses, systematic reviews, secondary analyses, and relevant narrative reviews published in English were considered. Particular emphasis was placed on high‐quality evidence, including the PROTECTION randomized trial, contemporary meta‐analyses, and consensus or expert reviews addressing cardiac surgery–associated acute kidney injury and perioperative metabolic interventions. Results The literature search identified 124 records; 18 articles were included in the final narrative synthesis after title, abstract, and full‐text evaluation. The selected literature comprised a multicenter randomized controlled trial, secondary analyses of randomized data, meta‐analyses/systematic reviews, narrative or expert reviews, and observational or mechanistic studies addressing CSA‐AKI. The evidence indicates that CSA‐AKI results from an interaction between altered renal perfusion, inflammation, ischemia–reperfusion injury, and CPB‐induced metabolic derangement. Intravenous amino acid infusion was consistently associated with reduced postoperative AKI incidence, particularly in patients with preexisting chronic kidney disease, without significant safety concerns. These findings support amino acid administration as a metabolic adjunct to goal‐directed perfusion rather than a standalone intervention. Conclusions Intravenous amino acid infusion is a recent strategy to reduce AKI in cardiac surgery. By targeting the CPB‐induced metabolic stress, amino acid administration complements goal‐directed perfusion and expands current AKI prevention paradigms beyond hemodynamic optimization alone. Future research should focus on CPB‐specific timing, dosing strategies, and integration of metabolic support into multimodal AKI prevention bundles.