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Recent Advances of Sarcopenia and Frailty in CKD pp 15–33Cite as

Molecular Mechanism of Muscle Wasting in CKD

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Abstract

Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and a decreased muscle endurance. Many insights have made into the molecular mechanisms of muscle atrophy in CKD. A persistent imbalance between protein synthesis and degradation causes a loss of muscle mass. A decrease in insulin/IGF-1-Akt-mTOR signaling and an increased ubiquitin-proteasome system (UPS) have emerged as inducers of muscle loss. During muscle wasting, abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in skeletal muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The binding of myostatin to its receptor ActRIIB stimulates the expression of Foxo-dependent atrogenes. An impaired mitochondrial function also contributes to reduced muscle endurance. Increased glucocorticoid, angiotensin II, parathyroid hormone, and protein-bound uremic toxin levels that are observed in CKD all have a negative effect on muscle mass and endurance. The loss of skeletal muscle mass during the progression of CKD further contributes to the development of renal failure. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages using animal models and clinical settings.

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Acknowledgement

We are grateful to Professor Masafumi Fukagawa, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Kanagawa, Japan, Dr. Kazutaka Matsushita and Dr. Motoko Tanaka, Department of Nephrology, Akebono Clinic, Kumamoto, Japan for their valuable advice in the preparation of this manuscript. Our work was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (KAKENHI 25460190; 16H05114), the Research Foundation for Pharmaceutical Sciences, Japan and The Nakatomi Foundation.

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  1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan

    Hiroshi Watanabe & Toru Maruyama

  2. Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan

    Yuki Enoki

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  1. Hiroshi Watanabe
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  2. Yuki Enoki
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  3. Toru Maruyama
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Correspondence to Hiroshi Watanabe .

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  1. Blood Purification Unit, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan

    Akihiko Kato

  2. Medical Science, Kawasaki Medical School, Kurashiki, Japan

    Eiichiro Kanda

  3. Department of Nephrology, Tokyo Medical University, Tokyo, Japan

    Yoshihiko Kanno

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Watanabe, H., Enoki, Y., Maruyama, T. (2020). Molecular Mechanism of Muscle Wasting in CKD. In: Kato, A., Kanda, E., Kanno, Y. (eds) Recent Advances of Sarcopenia and Frailty in CKD. Springer, Singapore. https://doi.org/10.1007/978-981-15-2365-6_2

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