Protein Energy Metabolism in Chronic Kidney Disease

CKD patients with protein energy wasting (PEW) have increased morbidity, mortality, and diminished quality of life. This dysfunctional metabolic state is characterized by anorexia, ineffective utilization of nutrients, and augmented muscle protein catabolism, which leads to loss of lean body mass. A multitude of factors contribute to PEW, including inflammation, oxidative stress, hormonal dysregulation, resistance to the actions of insulin and growth hormone, and metabolic acidosis. These factors trigger muscle breakdown through activation of the ubiquitin proteasome system, oxidation of branched-chain amino acids, and apoptosis. Several treatments for PEW have been proposed in the KDOQI guidelines, including nutritional goals to maintain protein stores. Potentially relevant treatments that have yielded controversial results so far include aerobic and resistance exercise, treatment with human growth hormone, and bicarbonate supplementation. Other potential treatments requiring additional study for safety and efficacy in humans include ghrelin administration and testosterone treatment. Understanding the etiology of this maladaptive metabolic state is important for development of new therapies for treatment of PEW. The current pathophysiology of PEW remains elusive and treatment of PEW in the CKD population remains difficult.