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

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 (2020). Parathyroid hormone and plasma phosphate are predictors of soluble α-klotho levels in adults of European descent. Journal of Clinical Endocrinology & Metabolism, 105(4):dgz232.

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Biochemistry
Life Sciences > Endocrinology
Life Sciences > Clinical Biochemistry
Health Sciences > Biochemistry (medical)
Uncontrolled Keywords:Clinical Biochemistry, Biochemistry, Endocrinology, Diabetes and Metabolism, Endocrinology, Biochemistry, medical
Language:English
Date:1 April 2020
Deposited On:07 Feb 2020 10:34
Last Modified:23 Oct 2024 01:35
Publisher:Oxford University Press
ISSN:0021-972X
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1210/clinem/dgz232
PubMed ID:31774122
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