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There are three isoforms of the Klotho protein: \u03b1Klotho, \u03b2Klotho and \u03b3Klotho. This review will focus on \u03b1Klotho due to its relevance as a biomarker in CKD. \u03b1Klotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease\u2013mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.<\/jats:p>","DOI":"10.3390\/ijms25031843","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease\u2013Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows"],"prefix":"10.3390","volume":"25","author":[{"given":"Julia","family":"Mart\u00edn-V\u00edrgala","sequence":"first","affiliation":[{"name":"Metabolismo \u00d3seo, Vascular y Enfermedades Inflamatorias Cr\u00f3nicas, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Redes de 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