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Kidney Int. 2018 Dec 28. pii: S0085-2538(18)30777-4. doi: 10.1016/j.kint.2018.10.010. [Epub ahead of print]

Emerging role of myostatin and its inhibition in the setting of chronic kidney disease.

Author information

1
Clinica Nefrologica, Dialisi, Trapianto, Università di Genova e Ospedale Policlinico San Martino, Genoa, Italy.
2
Clinica Nefrologica, Dialisi, Trapianto, Università di Genova e Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: gari@unige.it.
3
Department of Nephrology and Nutrition, Centre Hospitalier Lyon SUD, Carmen, CENS, University of Lyon, UCBL, Pierre Bénite, France.

Abstract

The past two decades have witnessed tremendous progress in our understanding of the mechanisms underlying wasting and cachexia in chronic kidney disease (CKD) and in other chronic illnesses, such as cancer and heart failure. In all these conditions wasting is an effect of the activation of protein degradation in muscle, a response that increases the risk of morbidity and mortality. Major recent advances in our knowledge on how CKD and inflammation affect cellular signaling include the identification of the myostatin (MSTN)/activin system, and its related transcriptional program that promotes protein degradation. In addition, the identification of the role of MSTN/activin in the vascular wall shows premise that its inhibition can better control or prevent some effects of CKD on vessels, such as accelerated atherosclerosis and vascular calcifications. In this review, we summarize the expanding role of MSTN activation in promoting muscle atrophy and the recent clinical studies that investigated the efficacy of MSTN/activin pathway antagonism in sarcopenic patients. Moreover, we also review the utility of MSTN inhibition in the experimental models of CKD and its potential advantages in CKD patients. Lessons learned from clinical studies on MSTN antagonism in sarcopenic patients tell us that the anabolic intervention is likely better if we use a block of the two ActRII receptors. At the same time, however, it is becoming clear that MSTN-targeted therapies should not be seen as a substitute for physical activity and nutritional supplementation which are mandatory to successfully manage patients with wasting.

KEYWORDS:

chronic kidney disease; inflammation; insulin resistance; nutrition

PMID:
30598193
DOI:
10.1016/j.kint.2018.10.010

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