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Parathyroid hormone and plasma phosphate are predictors of soluble α-klotho levels in adults of European descent

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Dhayat Nasser A, Pruijm Menno, Ponte Belen, Ackermann Daniel, Leichtle Alexander Benedikt, Devuyst Olivier, Ehret Georg, Guessous Idris, Pechère-Bertschi Antoinette, Pastor Johanne, Martin Pierre-Yves, Burnier Michel, Fiedler Georg-Martin, Vogt Bruno, Moe Orson W, Bochud Murielle, Fuster Daniel G,
Project Mechanisms of thiazide-induced glucose intolerance
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Original article (peer-reviewed)

Journal The Journal of Clinical Endocrinology & Metabolism
Page(s) 1 - 28
Title of proceedings The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgz232

Open Access

Type of Open Access Repository (Green Open Access)


AbstractContextα-klotho is an integral membrane protein, that serves as a co-receptor for fibroblast growth factor 23 (FGF23) in conjunction with cognate fibroblast growth factor receptors. Proteolytic cleavage sheds the ectodomain of α-klotho (soluble α-klotho) as an endocrine substance into blood, urine and cerebrospinal fluid.ObjectiveTo study the relationship of soluble α-klotho to mineral metabolism in the general population with mainly preserved kidney function.DesignCross-sectional analysis of the associations between soluble α-klotho with laboratory markers of markers of mineral metabolism in a population-based cohort.SettingThree centers in Switzerland including 1128 participants.MeasuresSoluble full-length α-klotho levels by a specific immunoassay and markers of mineral metabolism.ResultsThe median serum level of soluble α-klotho was 15.0 pmol/L. Multivariable analyses using α-klotho as outcome variable revealed a sex-by-parathyroid hormone (PTH) interaction: In men, PTH was positively associated with α-klotho levels whereas this association was negative in women. Plasma phosphate associated with soluble α-klotho levels in an age-dependent manner, changing from a positive association in young adults gradually to a negative association in the elderly. The decline of 1,25 (OH)2 vitamin D3 levels in parallel to the gradual impairment of kidney function was greatly attenuated in the setting of high circulating soluble α-klotho levels.ConclusionsSoluble α-klotho level is associated with plasma phosphate in an age-dependent manner and with PTH in a sex-dependent manner. Furthermore, our data reveal soluble α-klotho as a modulator of 1,25 (OH)2 vitamin D3 levels in individuals with preserved renal function.