Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

Abstract

Intradialytic protein catabolism is attributed to loss of amino acids in the dialysate. We investigated the effect of amino acid infusion during hemodialysis (HD) on muscle protein turnover and amino acid transport kinetics by using stable isotopes of phenylalanine, leucine, and lysine in eight patients with end-stage renal disease (ESRD). Subjects were studied at baseline (pre-HD), 2 h of HD without amino acid infusion (HD-O), and 2 h of HD with amino acid infusion (HD+AA). Amino acid depletion during HD-O augmented the outward transport of amino acids from muscle into the vein. Increased delivery of amino acids to the leg during HD+AA facilitated the transport of amino acids from the artery into the intracellular compartment. Increase in muscle protein breakdown was more than the increase in synthesis during HD-O (46.7 vs. 22.3%, P < 0.001). Net balance (nmol·min−1·100 ml −1) was more negative during HD-O compared with pre-HD (−33.7 ± 1.5 vs. −6.0 ± 2.3, P < 0.001). Despite an abundant supply of amino acids, the net balance (−16.9 ± 1.8) did not switch from net release to net uptake. HD+AA induced a proportional increase in muscle protein synthesis and catabolism. Branched chain amino acid catabolism increased significantly from baseline during HD-O and did not decrease during HD+AA. Protein synthesis efficiency, the fraction of amino acid in the intracellular pool that is utilized for muscle protein synthesis decreased from 42.1% pre-HD to 33.7 and 32.6% during HD-O and HD+AA, respectively ( P < 0.01). Thus amino acid repletion during HD increased muscle protein synthesis but did not decrease muscle protein breakdown.

Sarcopenia: A Major Challenge in Elderly Patients with End-Stage Renal Disease

“…They are not built into the muscles, as we would expect during muscle reconstruction after proteolysis. Amino acids are transported to the liver where they are utilized probably to the synthesis of acute phase proteins [7, 60]. Experimental attempts to block TNF α and NF κ B inhibited skeletal muscle proteolysis [61, 62].…”

Physical Exercise in Patients with Severe Kidney Disease

“…There is a gradual increase in muscle wasting as kidney function deteriorates towards the need for RRT [22], and defective protein metabolism is observed in those treated with regular dialysis [23] suggesting that both renal failure itself and the dialysis process contribute to this catabolic state [24,25]. Specifically HD has been shown to promote muscle and whole body protein degradation [24,26].…”

“…There is a gradual increase in muscle wasting as kidney function deteriorates towards the need for RRT [22], and defective protein metabolism is observed in those treated with regular dialysis [23] suggesting that both renal failure itself and the dialysis process contribute to this catabolic state [24,25]. Specifically HD has been shown to promote muscle and whole body protein degradation [24,26]. Chronic metabolic acidosis (which occurs in nearly all patients with advanced CKD) contributes to this increased protein degradation [23] by activation of the ubiquitin-proteasome pathway [27], possibly initiated by impairing the transport and utilization of amino acids [28].…”

Inflammation in Chronic Kidney Disease

“…Consequently, clinical studies in CKD patients have shown links between inflammatory cytokines and muscle wasting [3,75e77]. A main mechanism of inflammationinduced wasting is via activation of NF-kB and ATPubiquitin-dependent proteolytic pathways (leading to cleavage of a characteristic 14 kDa actin fragment) that cause muscle wasting [78]. As Raj et al [79] observed ineffective utilization of exogenous amino acids for muscle protein synthesis during HD, they hypothesized that increased skeletal muscle expression of IL-6 further augmented muscle protein catabolism in ESRD.…”