Chapter 74 - Amino Acid Turnover, Protein Metabolism, and Nitrogen Balance in Acute Kidney Injury

Abstract

Critical illness induces an inflammatory milieu in patients that is exacerbated by acute kidney injury (AKI) and results in derangements in protein metabolism. Proteins are polymers of amino acids (AAs), with nitrogen as a fundamental component. Metabolic equilibrium between intake/synthesis and degradation/loss exists physiologically. Protein synthesis and muscle hypertrophy are promoted by activity-driven insulin-like growth factor-1 action and downstream induction of autocrine and paracrine activities. These are counterbalanced by protein breakdown via the ubiquitin-proteasome pathway. The oxidative stress and catabolic hormonal surge during critical illness and AKI tip the balance into net protein catabolism, with increased hepatic gluconeogenesis, ureagenesis, and disordered plasma AA profile. These are worsened by metabolic acidosis and restricted intake with acute illness and oligoanuric state. Protein catabolism translates to early and severe muscle wasting in critically ill patients, especially with multiorgan failure. Renal replacement therapy (RRT) facilitates nutritional support by volume and azotemic control during AKI but leads to undesired losses, including AAs because of their small molecular weight and membrane adsorption of proteins. AAs are lost selectively at 5% to 20% of daily intake but account for less than 10% of total nitrogen loss, the majority being urea nitrogen. Corresponding protein loss during RRT can exceed 2 g/kg/day. However, purported benefits of early, enhanced nutritional support and increased protein delivery during initial acute illness on patient outcomes are not proven by recent large-scale randomized controlled trials (RCTs). Individualized nutritional management during recovery phase of AKI, with objective assessments of nitrogen balance during RRT, muscle mass indices, and early patient mobilization, are desirable for future research.