Metabolic Effects of Branched-Chain Amino Acids and Keto Acids: Mechanisms Independent of Protein Intake?

THE HUNGARIAN Ketosteril (Fresenius Kabi, Bad Homburg, Germany) Follow-Up Cohort Study (1995 to 1997) and several clinical studies evaluated the efficacy of protein-restricted diets (0.3 to 0.6 g protein/kg body weight/day) supplemented with keto acids/amino acids (KAs) on the progression and metabolic complications of chronic kidney disease (CKD). In all studies, metabolic complications were improved, and in the majority of studies, the decline in glomerular filtration rate was reduced compared with a moderate respectively protein-unrestricted diet. The rationale for the use of keto acids/amino acids within the therapeutic concept of low protein diets (0.3 to 0.6 g protein/kg body weight/ day) is based on the well-known antihyperfiltrative effects of branched-chain amino acids (BCAAs) and keto acids. Furthermore, Tutttle et al. studied the cellular mechanisms of glomerular injury induced by amino acids, with or without high glucose. Mesangial cells exposed to a mixture of amino acids, designed to resemble protein feeding, produced a profibrotic response as a consequence of advanced glycation end products and reactive oxygen species formation, presumably induced by the increased availability of amino groups for glycation reactions.