IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2013;6(7):532-539

Original Article
Skeletal muscle mitochondrial depletion and dysfunction in chronic kidney disease

Puya G Yazdi, Hamid Moradi, Jia-Ying Yang, Ping H Wang, Nasratola D Vaziri

Division of Nephrology and Hypertension, Center for Diabetes Research and Treatment, University of California, Irvine, California, USA.
These authors have equally contributed to this project.

Received May 24, 2013; Accepted June 26, 2013; Epub August 1, 2013; Published August 15, 2013

Abstract: Advanced chronic kidney disease (CKD) is associated with impaired exercise capacity, skeletal muscle dysfunction, and
oxidative stress. Mitochondria are the primary source for energy production and generation of reactive oxygen species (ROS).
Mitochondrial state 3 respiration, mitochondrial complex I enzyme activity, and tissue porin/actin ratio were determined in the
gastrocnemius muscle of male SD rats 14 weeks after 5/6 nephrectomy (CKD) or sham-operation (control). The CKD group exhibited
azotemia, hypertension, significant reduction (-39%) of state 3 mitochondrial respiration, and a significant increase in the mitochondrial
complex I enzyme activity. The latter is the first step in oxidative phosphorylation, a process linked to production of ROS. These
abnormalities were associated with a significant reduction in muscle porin/β actin ratio denoting substantial reduction of mitochondrial
mass in skeletal muscle of animals with CKD. CKD results in impaired mitochondrial respiration, reduced muscle mitochondrial
mass, depressed energy production and increased ROS generation in the skeletal muscle. These events can simultaneously
contribute to the reduction of exercise capacity and oxidative stress in CKD. (IJCEM1305016).

Keywords: End stage renal disease, oxidative stress, muscle weakness, exercise capacity, uremia

Address correspondence to: Dr. Nasratola D Vaziri, Division of Nephrology and Hypertension, Schools of Medicine and Biological
Science, University of California, Irvine. Phone: 714-456-5142; Fax: 714-456-6034; E-mail: ndvaziri@uci.edu