Parathyroid Hormone And Plasma Phosphate Are Predictors Of Soluble Alpha-Klotho Levels In Adults Of European Descent

Context alpha-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 alpha-klotho (soluble alpha-klotho) as an endocrine substance into blood, urine, and cerebrospinal fluid.Objective To study the relationship of soluble alpha-klotho to mineral metabolism in the general population with mainly preserved kidney function.Design Cross-sectional analysis of the associations between soluble alpha-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 alpha-klotho levels by a specific immunoassay and markers of mineral metabolism.Results The median serum level of soluble alpha-klotho was 15.0 pmol/L. Multivariable analyses using alpha-klotho as the outcome variable revealed a sex-by-PTH interaction: In men, PTH was positively associated with alpha-klotho levels, whereas this association was negative in women. Plasma phosphate associated with soluble alpha-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 D-3 levels in parallel to the gradual impairment of kidney function was greatly attenuated in the setting of high circulating soluble alpha-klotho levels.Conclusions Soluble alpha-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 alpha-klotho as a modulator of 1,25 (OH)(2) vitamin D-3 levels in individuals with preserved renal function.