Dietary Amino Acid Availability and Anabolic Signaling Molecule Phosphorylation is Blunted in Maintenance Hemodialysis Patients

Abstract

Skeletal muscle mass loss is a common feature in patients with renal failure receiving maintenance hemodialysis (MHD) therapy. Dietary protein (amino acids) is one of the main anabolic stimuli to skeletal muscle tissue in humans, and impairments to anabolic stimuli over time may lead to muscle mass loss. However, there are major gaps in our knowledge of how muscle mass is regulated by protein intake in MHD patients. PURPOSE: To compare dietary protein digestion and absorption kinetics and phosphorylation of anabolic signaling proteins after mixed meal ingestion in MHD patients and age- and BMI-matched controls. METHODS: 8 MHD patients (age: 56±5 y; BMI: 32±2 kg/m2) and 8 controls (age: 50±2 y; BMI: 31±1 kg/m2) received primed continuous infusions of L-[1-13C]leucine and ingested a mixed meal (546 kcal, 20 g protein, 59 g carbohydrate, 26 g fat) with protein provided as intrinsically L-[5,5,5-2H ]leucine labeled eggs. Breath, blood, and muscle biopsies were collected to determine amino acid concentrations, leucine enrichments, and phosphorylation of mTORC1 on Ser2448 during a 5 postprandial period. RESULTS: Postprandial release of dietary leucine into circulation over 5 h was reduced in MHD patients (41±5%) vs. controls (61±4%; P=0.03). The feeding-mediated increase in mTORC1 phosphorylation was blunted in MHD patients (0.6-fold above basal) vs. controls (1.1-fold above basal; P=0.006) at 5 h of the postprandial period. CONCLUSION: Our data demonstrated impaired kinetics of digestion/absorption of dietary proteins and reduced postprandial plasma amino acid availability in circulation after mixed meal ingestion in MHD patients when compared to age- and BMI-matched controls. This diminished dietary amino acid availability may have partly contributed to the blunted anabolic signaling mechanisms in MHD patients. Supported by the Egg Nutrition Center (ENC)