Parathyroid hormone and plasma phosphate are predictors of soluble α-Klotho levels in adults of european descent

Context α-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-klotho (soluble α-klotho) as an endocrine substance into blood, urine, and cerebrospinal fluid. Objective To study the relationship of soluble α-klotho to mineral metabolism in the general population with mainly preserved kidney function. Design Cross-sectional analysis of the associations between soluble α-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-klotho levels by a specific immunoassay and markers of mineral metabolism. Results The median serum level of soluble α-klotho was 15.0 pmol/L. Multivariable analyses using α-klotho as the outcome variable revealed a sex-by-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. Conclusions Soluble 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.