Effects of Low-Protein, and Supplemented Very Low-Protein Diets, on Muscle Protein Turnover in Patients With CKD

Abstract

Introduction: Early studies have shown that patients with chronic kidney disease (CKD) are able to maintain nitrogen balance despite significantly lower protein intake, but how and to what extent muscle protein metabolism adapts to a low-protein diet (LPD) or to a supplemented very LPD (sVLPD) is still unexplored.

Methods: We studied muscle protein turnover by the forearm perfusion method associated with the kinetics of ²H-phenylalanine in patients with CKD: (i) in a parallel study in subjects randomized to usual diet (1.1 g protein/kg, n = 5) or LPD (0.55 g protein/kg, n = 6) (Protocol 1); (ii) in a crossover, self-controlled study in subjects on a 0.55 g/kg LPD followed by a sVLPD (0.45 g/kg + amino/ketoacids 0.1 g/kg, n = 6) (Protocol 2).

Results: As compared with a 1.1 g/kg containing diet, a 0.55 g/kg LPD induced the following: (i) a 17% to 40% decrease in muscle protein degradation and net protein balance, respectively, (ii) no change in muscle protein synthesis, (iii) a slight (by approximately 7%, P < 0.06) decrease in whole-body protein degradation, and (iv) an increase in the efficiency of muscle protein turnover. As compared with an LPD, an sVLPD induced the following: (i) no change in muscle protein degradation, and (ii) an approximately 50% decrease in the negative net protein balance, and an increase in the efficiency of muscle protein turnover.

Conclusion: The results of these studies indicate that in patients with CKD the adaptation of muscle protein metabolism to restrained protein intake can be obtained via combined responses of protein degradation and the efficiency of recycling of amino acids deriving from protein breakdown.

Keywords: amino acids; chronic kidney disease; ketoacids; low-protein diet; nutrition.

Figure 1

The design of the study in Protocol 1. Protocol 1 was a randomized, parallel design study in which subjects were randomly divided into 2 groups that received either a 0.55-g/kg low-protein diet (LPD) or a 1.1-g/kg per day protein diet. During the run-in phase, patients were instructed on a stable diet. In the LPD arm (n = 6), forearm protein turnover was evaluated as follows: (i) after a 6-week period of a 1.1-g/kg per day protein diet, and (ii) 12 weeks after an LPD (initially 0.8 and subsequently 0.55 g/kg). In the 1.1-g protein/kg arm (n = 5), muscle protein turnover was studied as follows: (i) after a 6-week period of a 1.1-g/kg per day protein diet, and (ii) 12 weeks after the patients continued the same diet. Arrows indicate forearm protein turnover studies.

Figure 2

The design of the study in Protocol 2. Protocol 2 was designed to study the muscle metabolic responses to an amino acid/ketoacid (AA/KA)-supplemented (0.1 g/kg) very low protein diet (VLPD) (0.45 g/kg), as compared to a 0.55-g/kg low-protein diet (LPD). This protocol was a prospective, crossover trial, with patients serving as their own controls. The study consisted of three 6-week consecutive periods: the baseline period (LPD, 0.55 g/kg), the treatment period (VLPD 0.45 g/kg + AA/KA 0.1 g/kg), and the washout period (LPD, 0.55 g/kg). Arrows indicate forearm protein turnover studies.

Figure 3

The magnitude of daily protein turnover requires reutilization of amino acids released by protein breakdown for protein synthesis. In patients with chronic kidney disease (CKD) and diets containing 1.1 g/kg protein, 64% of amino acid phenylalanine is recycled into protein synthesis. During a low-protein diet (0.55 g/kg), the entity of amino acid recycling increases to 75%, indicating greater efficiency of protein turnover.

Figure 4

The contribution of muscle to whole-body protein degradation declines markedly during a low-protein diet. a = P < 0.05 versus the 1.1-g/kg diet.

Figure 5

In patients with chronic kidney disease (CKD) and diets containing 0.55 g/kg protein, 72% of amino acid (AA) phenylalanine is recycled into protein synthesis. During a very low–protein diet (0.45 g/kg) supplemented with AA and ketoacids (AA/KA) (0.1 g/kg), the entity of AA recycling increases to 83%, indicating greater efficiency of protein turnover.