Muscle amino acid metabolism and the control of muscle protein turnover in patients with chronic renal failure.

Abstract

Malnutrition is frequently observed in patients with end-stage renal disease. Studies indicate that poor nutritional status plays a major role among factors adversely affecting patients outcome. Therefore prevention and treatment of malnutrition in renal patients is a major issue. In this article the potential mechanisms for alterations in muscle protein metabolism in uremia are explored. Malnutrition has been mainly attributed to inadequate intake of nutrients, superimposed illnesses, or both. However, both clinical and experimental evidence show that uremia per se may adversely affect the control of muscle protein and amino acid metabolism. Available evidence suggests that catabolic factors appear to be distinct for patients at different stages of chronic renal failure and require different modalities of treatments. Both nutritional requirements and the prevalence of malnutrition increase as end-stage renal disease progresses. Muscle protein degradation is increased by metabolic acidosis, which is often found in uremic patients. Another relevant, but less proven cause for increased protein degradation is insulin resistance. Furthermore, specific defects in muscle amino acid metabolism, resistance to growth hormone, insulin-like growth factor 1, or a very low protein intake can reduce muscle protein synthesis. Finally, the hemodialytic procedure per se can stimulate protein breakdown or reduce protein synthesis. All these factors may potentiate the effects of concurrent catabolic illnesses, anorexia, and physical inactivity often found in uremic patients.