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Uremic Solutes and Sarcopenia

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Uremic Toxins and Organ Failure

Abstract

Sarcopenia in chronic kidney disease (CKD) is characterized by muscle wasting and decreased muscle endurance. Many insights have been 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 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. The increased ROS and inflammatory cytokine induce the expression of myostatin, a negative regulator of muscle growth. An impaired mitochondrial function also contributes to reduced muscle endurance. Uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and parathyroid hormone have a negative effect on muscle mass and endurance by affecting protein synthesis and degradation in addition to mitochondrial function in skeletal muscle. Some potential therapeutic approaches based on the molecular mechanisms of muscle wasting in CKD are currently in the testing stages.

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Acknowledgments

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, Hiromasa Kato, Hitoshi Maeda & Toru Maruyama

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

    Yuki Enoki

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  1. Hiroshi Watanabe
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  2. Hiromasa Kato
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Correspondence to Hiroshi Watanabe .

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  1. Department of Pharmacy, Kumamoto University Hospital, Kumamoto University, Kumamoto, Japan

    Hideyuki Saito

  2. Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takaaki Abe

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Watanabe, H., Kato, H., Enoki, Y., Maeda, H., Maruyama, T. (2020). Uremic Solutes and Sarcopenia. In: Saito, H., Abe, T. (eds) Uremic Toxins and Organ Failure. Springer, Singapore. https://doi.org/10.1007/978-981-15-7793-2_9

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