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

DOI
Publisher DOI
PubMed ID
31774122
Abstract
Context: α-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.
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 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.
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.
Date Issued
2020-04-01
Publication Type
Article
Subject(s)
Subjects
soluble α-Klotho
•
parathyroid hormone
•
phosphate
Language(s)
en
Author(s)
Pruijm, Menno
Ponte, Belen
Devuyst, Olivier
Ehret, Georg
Guessous, Idris
Pechère-Bertschi, Antoinette
Pastor, Johanne
Martin, Pierre-Yves
Burnier, Michel
Moe, Orson
Bochud, Murielle
Additional Credits
Journal
The journal of clinical endocrinology and metabolism
Publisher
Oxford University Press
ISSN
1945-7197
Access(Rights)
open.access
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