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    Myostatin and activin A induce muscle wasting by activating the ubiquitin proteasome system and inhibiting the Akt/mammalian target of rapamycin pathway. In chronic kidney disease (CKD), myostatin and activin A plasma concentrations are increased, but it is unclear if there is increased production or decreased renal clearance. We measured myostatin and activin A concentrations in 232 CKD patients and studied their correlation with estimated glomerular filtration rate (eGFR). We analyzed the myostatin gene (MSTN) expression in muscle biopsies of hemodialysis (HD) patients. We then measured circulating myostatin and activin A in plasma and the Mstn and Inhba expression in muscles, kidney, liver and heart of two CKD mice models (adenine and 5/6 nephrectomy models). Finally, we analyzed whether the uremic toxin indoxyl sulfate (IS) increased Mstn expression in mice and cultured muscle cells. In patients, myostatin and activin A were inversely correlated with eGFR. MSTN expression was lower in HD patients' muscles (vastus lateralis) than in controls. In mice with CKD, myostatin and activin A blood concentrations were increased. Mstn was not upregulated in CKD mice tissues. Inha was upregulated in kidney and heart. Exposure to IS did not induce Mstn upregulation in mouse muscles and in cultured myoblasts and myocytes. During CKD, myostatin and activin A blood concentrations are increased. Myostatin is not overproduced, suggesting only an impaired renal clearance, but activin A is overproduced in the kidney and heart. We propose to add myostatin and activin A to the list of uremic toxins. © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.

    Citation

    Stanislas Bataille, Laetitia Dou, Marc Bartoli, Marion Sallée, Julien Aniort, Borhane Ferkak, Rania Chermiti, Nathalie McKay, Nathalie Da Silva, Stéphane Burtey, Stéphane Poitevin. Mechanisms of myostatin and activin A accumulation in chronic kidney disease. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2022 Jun 23;37(7):1249-1260

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    PMID: 35333341

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