Chronic kidney disease and acquired mitochondrial myopathy

被引:37
作者
Rao, Madhumathi [1 ]
Jaber, Bertrand L. [2 ]
Balakrishnan, Vaidyanathapuram S. [2 ]
机构
[1] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA
[2] Tufts Univ, St Elizabeths Med Ctr, Sch Med, Dept Med,Div Nephrol, 736 Cambridge St, Boston, MA 02135 USA
关键词
chronic kidney disease; mitochondrial biogenesis; mitochondrial dysfunction; sarcopenia; CHRONIC-RENAL-FAILURE; DNA COPY NUMBER; SKELETAL-MUSCLE; OLDER-ADULTS; BODY-COMPOSITION; CONTROLLED-TRIAL; L-CARNITINE; HEMODIALYSIS-PATIENTS; EXERCISE CAPACITY; PHYSICAL FUNCTION;
D O I
10.1097/MNH.0000000000000393
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Sarcopenia and muscle weakness contribute to fragility and limit exercise tolerance among patients with CKD. This review focuses on the role of reduction in mitochondrial mass and function in the myopathy associated with CKD, causes for these muscle mitochondrial abnormalities, and potential therapeutic interventions that may improve mitochondrial biogenesis and function as well as skeletal muscle function and performance in patients with CKD. Recent findings Multiple abnormalities of mitochondrial structure, function, and composition have been shown in both experimental models and patients with CKD. A significant reduction in mitochondrial respiratory function and an increase in mitochondrial complex 1 enzyme activity has been demonstrated in the muscle tissue of male Sprague-Dawley rats following 5/6 nephrectomy. These changes were associated with a substantial reduction in skeletal muscle mitochondrial mass. In patients with CKD, in-vivo magnetic resonance and optical spectroscopy show significantly elevated resting skeletal muscle oxygen consumption and lower mean mitochondrial coupling ratio indicating disrupted muscle mitochondrial metabolism and uncoupling of oxidative phosphorylation. Skeletal muscle biopsies from patients with advanced CKD show lower mitochondrial volume density and mitochondrial DNA (mtDNA) copy number than controls. Summary Advanced CKD is associated with decreased exercise capacity, skeletal muscle weakness, and muscle atrophy. Impaired mitochondrial respiratory function, reduced muscle mitochondrial mass, and decreased energy production in skeletal muscle play a critical role in this 'acquired mitochondrial myopathy' of CKD. It is reasonable, therefore, to develop therapeutic interventions that enhance mitochondrial biogenesis and function as well as skeletal muscle function and performance in patients with CKD.
引用
收藏
页码:113 / 120
页数:8
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