Amino Acid Transport Kinetics and Protein Turnover in Hemodialysis

Abstract

Background: Protein metabolism is abnormal in patients with end-stage renal disease. However, the etiology of abnormal protein turnover is unclear. Also the role of hemodialysis on protein turnover remains controversial. Abnormal protein metabolism could be due to malnutrition or due to abnormal amino acid transport kinetics Hypothesis: 1) Amino acid transport is abnormal in uremia, 2) Hemodialysis increases fractional protein synthesis rate and c) Net protein accretion is negative during hemodialysis because of increased catabolism. Aim: 1) To study the impact of uremia and hemodialysis on intracellular amino acid transport kinetics and 2) Quantify the fractional protein synthesis rate and degradation in a uremic state and during hemodialysis Methods: Protein turnover and amino acid transport kinetics using stable isotopes of phenylalanine in 2 patients and 2 controls. The patients were placed on a standard diet (1.2 gm/Kg protein and 35 Kcal/Kg) for 2 weeks prior to the study. Acidosis as corrected by NaHCO3 supplementation. Amino acid transport and protein turnover were estimated by compartmental model and precursor product approach respectively. Results: Mean protein intake and HCO3 were 1.4 ± 1 gm/day and 26.8 ± 4.1 meq/L respectively. Inward transport (11.2 ± 2.6 vs. 9.8 ± 2.1 nmol/min−1/100 ml leg−1) and outward transport (10.2 ± 1.2 vs.11.0 ± 1.6 l nmol/min−1/100 ml leg−1) were not different before and during HD. Inward and outward transport in controls were 12.6 ± 3.7 and 16.2 ± 3.5 nmol/min−1/100 ml leg−1 respectively. Protein synthesis was higher than catabolism in the pre-dialysis phase (156.8 ± 66.1 vs. 144.3 ± 53.7 nmol/min/ml leg-1, p = NS), but catabolism was higher than synthesis during HD (172.3 ± 20.5 vs. 186.8 ± 25.8 nmol/min/ml leg-1, p = NS). Protein synthesis and catabolism in controls were 110.8 ± 13.5 and 127.4 ± 12.7 nmol/min/ml leg-1. Conclusion: 1. Inward and outward transport of amino acids are not altered by renal failure or hemodialysis. 2. Protein turnover is increased during hemodialysis, with net balance favoring catabolism