Impaired skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease

Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity

“…The changes in mitochondrial parameters were correlated with the baseline level, with a higher benefit in subjects with greater dysfunction. The same improvement was observed for resting muscle oxygen uptake, found to be abnormally high during deconditioning [ 35 ], in MS [ 24 ] and in other chronic conditions [ 40 ]. It is known that low rates of physical activity, typical of people with disabilities, trigger deconditioning with disuse-induced changes in muscle [ 41 , 42 ].…”

Mitochondrial Dysfunction in Kidney Disease and Uremic Sarcopenia

“…Patients with CKD develop impaired mitochondrial energetics associated with the disease severity in skeletal muscle ( Kestenbaum et al, 2020 ). CKD mice with muscle atrophy have decreased mitochondrial activity and amount, metabolism related to AMP-activated protein kinase (AMPK) phosphorylation and Pgc1 α gene expression ( Tamaki et al, 2014 ).…”

Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease

“…Several studies have implicated skeletal muscle mitochondria as a contributor to CKDassociated myopathy (12)(13)(14)(15)(16)(17)(18). Reports in both animal models and human CKD muscle commonly observe decreased mitochondrial content (12,14,19), impaired mitochondrial respiration (12,18,20,21), and elevated oxidative stress (22,23). Because mitochondria are the primary site for ATP production and generation of the free energy for ATP hydrolysis (i.e.…”

“…capacity to power cellular work), impairment in mitochondrial energy transduction is likely to be a significant factor determining physical function and exercise tolerance in CKD patients. Indeed, recent clinical studies have confirmed that muscle oxidative capacity, measure by magnetic resonance spectroscopy, is strongly associated with physical performance in CKD patients (21,24). Despite these reports, a comprehensive understanding of how impaired kidney function alters skeletal muscle mitochondrial health is lacking.…”

“…muscle-related symptoms often develop over long periods of time and epidemiological and cross-sectional clinical studies have reported strong associations between the severity of myopathy and kidney function (GFR or diagnosed CKD stage)(42)(43)(44). To date, much of the CKD literature examining the basis for myopathy has focused on These metabolic changes were coincident with increased muscle protein degradation and muscle atrophy, but normal contractile performance in ex vivo muscle preparations.Although impaired mitochondrial respiration has been previously reported in both preclinical CKD models and human patients(14,15,17,19,21), the molecular mechanisms underlying these changes have not been defined. In this study, a comprehensive mitochondrial phenotyping analysis identified matrix dehydrogenase as the principal site of impaired energy transduction.…”