Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients

Introduction: Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy. Methods: Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m²) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m²) received primed continuous L-[ring-²H₅]phenylalanine and L-[1-¹³C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-²H₃]leucine-labeled eggs. Results: Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004). Conclusions: MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.