Parathyroid Hormone and Plasma Phosphate Are Predictors of Soluble αあるふぁ-Klotho Levels in Adults of European Descent

Dhayat, Nasser A Pruijm, Menno Ponte, Belen Ackermann, Daniel Leichtle, Alexander Benedikt Devuyst, Olivier [UCL] 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 et al.[show all]

Context: αあるふぁ-klotho is an integral membrane protein that serves as a coreceptor for fibroblast growth factor 23 (FGF23) in conjunction with cognate fibroblast growth factor receptors. Proteolytic cleavage sheds the ectodomain of αあるふぁ-klotho (soluble αあるふぁ-klotho) as an endocrine substance into blood, urine, and cerebrospinal fluid. Objective: To study the relationship of soluble αあるふぁ-klotho to mineral metabolism in the general population with mainly preserved kidney function. Design: Cross-sectional analysis of the associations between soluble αあるふぁ-klotho with laboratory markers of markers of mineral metabolism in a population-based cohort. Setting: Three centers in Switzerland including 1128 participants. Measures: Soluble full-length αあるふぁ-klotho levels by a specific immunoassay and markers of mineral metabolism. Results: The median serum level of soluble αあるふぁ-klotho was 15.0 pmol/L. Multivariable analyses using αあるふぁ-klotho as the outcome variable revealed a sex-by-PTH interaction: In men, PTH was positively associated with αあるふぁ-klotho levels, whereas this association was negative in women. Plasma phosphate associated with soluble αあるふぁ-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あるふぁ-klotho levels. Conclusions: Soluble αあるふぁ-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あるふぁ-klotho as a modulator of 1,25 (OH)2 vitamin D3 levels in individuals with preserved renal function.