Uremic Solutes and Sarcopenia

Sarcopenia in chronic kidney disease (CKD) is characterized by muscle wasting and decreased muscle endurance. Many insights have been made into the molecular mechanisms of muscle atrophy in CKD. A persistent imbalance between protein synthesis and degradation causes a loss of muscle mass. A decrease in insulin/IGF-1-Akt-mTOR signaling and an increased ubiquitin–proteasome system have emerged as inducers of muscle loss. During muscle wasting, abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in skeletal muscle. The increased ROS and inflammatory cytokine induce the expression of myostatin, a negative regulator of muscle growth. An impaired mitochondrial function also contributes to reduced muscle endurance. Uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and parathyroid hormone have a negative effect on muscle mass and endurance by affecting protein synthesis and degradation in addition to mitochondrial function in skeletal muscle. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages.