Uremic Myopathy and Mitochondrial Dysfunction in Kidney Disease

Area of Science:

• Muscle physiology
• Renal medicine
• Metabolic pathways

Background:

• Chronic kidney disease (CKD) is linked to muscle structure and function alterations, impacting patient outcomes.
• Mitochondrial metabolism plays a crucial role in maintaining muscle homeostasis and is implicated in CKD-related muscle dysfunction.

Purpose of the Study:

• To investigate the roles of oxidative metabolism, glycolysis, and fatty acid oxidation in muscle metabolism within a CKD context.
• To elucidate the specific metabolic shifts contributing to muscle dysfunction in CKD.

Main Methods:

• Adenine-induced chronic kidney disease (CKD) model in mice.
• Analysis of muscle weight, fiber type proportion, and protein expression.
• In vitro studies using myotubes exposed to uremic serum to assess oxygen consumption and lactate production.

Main Results:

• CKD mice exhibited significant muscle weight loss and reduced fiber count in extensor digitorum longus (EDL) muscle.
• Decreased expression of oxidative phosphorylation proteins and increased expression of glycolytic enzymes/transporters were observed in CKD muscle.
• In vitro, uremic myotubes showed reduced glucose-dependent oxygen consumption but preserved fatty acid oxidation, alongside increased lactate production.

Conclusions:

• Adenine-induced CKD in mice results in sarcopenia characterized by a metabolic shift towards increased glycolysis, without significant changes in muscle fiber structure.
• In vitro models suggest that while glucose utilization is impaired, fatty acid utilization remains preserved in uremic myopathy.