{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:54Z","timestamp":1787026674815,"version":"build-2736575974"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Chronic kidney disease (CKD) is a systemic disorder in which sarcopenia serves as a critical driver of frailty and mortality. However, the \u201ckidney-muscle axis\u201d remains conceptually fragmented, often confounded by the overlapping definitions of protein-energy wasting (PEW) and cachexia. This review argues that CKD-associated sarcopenia is not driven by isolated myokines, but rather by a clearance-distorted, inflammation-coupled signaling network. We first disambiguate sarcopenia from PEW and cachexia, distinguishing canonical myokines from mediators whose interpretive value is altered by uremia. We then propose a framework organized around four pillars: hypercatabolism, anabolic resistance, mitochondrial dysfunction and bioenergetic remodeling, and context-dependent inflammatory signaling. Within this context, we reinterpret key mediators, including myostatin, growth differentiation factor 15 (GDF-15), insulin-like growth factor 1 (IGF-1), irisin, and interleukin-6 (IL-6), emphasizing that their circulating levels reflect a complex entanglement of altered secretion, impaired renal clearance, and tissue-specific resistance. While the kidney-to-muscle vector is well-supported, direct muscle-to-kidney feedback remains less established. By framing myokine dysregulation as a mechanistic interface, this review aims to refine causal inference and support the development of targeted therapies for muscle wasting in CKD.<\/jats:p>","DOI":"10.3389\/fmed.2026.1868285","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:46:59Z","timestamp":1781239619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Crosstalk in the kidney-muscle axis: myokines and muscle-relevant mediators in chronic kidney disease-associated sarcopenia"],"prefix":"10.3389","volume":"13","author":[{"given":"Ran","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: an update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int Suppl (2011)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s12882-022-02794-8","article-title":"Targeting inflammation for the treatment of diabetic kidney disease: a five-compartment mechanistic model","volume":"23","author":"Hofherr","year":"2022","journal-title":"BMC Nephrol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/j.ekir.2020.09.040","article-title":"Worldwide disparity in the relation between CKD prevalence and kidney failure risk","volume":"5","author":"van Rijn","year":"2020","journal-title":"Kidney Int Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"afac220","DOI":"10.1093\/ageing\/afac220","article-title":"Sarcopenia definition, diagnosis and treatment: consensus is growing","volume":"51","author":"Sayer","year":"2022","journal-title":"Age Ageing"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000448247","article-title":"Oral drugs related with muscle wasting and sarcopenia. 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