Significance: An estimated 700 million people globally suffer from chronic kidney disease (CKD). In addition to increasing cardiovascular disease risk, CKD is a catabolic disease that results in a loss of muscle mass and function, which are strongly associated with mortality and a reduced quality of life. Despite the importance of muscle health and function, there are no treatments available to prevent or attenuate the myopathy associated with CKD. Recent Advances: Recent studies have begun to unravel the changes in mitochondrial and redox homeostasis within skeletal muscle during CKD. Impairments in mitochondrial metabolism, characterized by reduced oxidative phosphorylation, are found in both rodents and patients with CKD. Associated with aberrant mitochondrial function, clinical and preclinical findings have documented signs of oxidative stress, although the molecular source and species are ill-defined. Critical Issues: First, we review the pathobiology of CKD and its associated myopathy, and we review muscle cell bioenergetics and redox biology. Second, we discuss evidence from clinical and preclinical studies that have implicated the involvement of mitochondrial and redox alterations in CKD-associated myopathy and review the underlying mechanisms reported. Third, we discuss gaps in knowledge related to mitochondrial and redox alterations on muscle health and function in CKD. Future Directions: Despite what has been learned, effective treatments to improve muscle health in CKD remain elusive. Further studies are needed to uncover the complex mitochondrial and redox alterations, including post-transcriptional protein alterations, in patients with CKD and how these changes interact with known or unknown catabolic pathways contributing to poor muscle health and function. Antioxid. Redox Signal. 38, 318-337.
Keywords: cachexia; metabolism; renal; skeletal muscle; uremia.