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; Bochud, Murielle; Fuster, Daniel G. (2020). Parathyroid hormone and plasma phosphate are predictors of soluble α-klotho levels in adults of European descent. The journal of clinical endocrinology and metabolism, 105(4) Oxford University Press 10.1210/clinem/dgz232

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

UniBE Contributor:

Dhayat, Nasser; Ackermann, Daniel; Leichtle, Alexander Benedikt; Fiedler, Georg Martin; Vogt, Bruno and Fuster, Daniel Guido

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1945-7197

Publisher:

Oxford University Press

Language:

English

Submitter:

Nasser Dhayat

Date Deposited:

03 Dec 2019 13:00

Last Modified:

14 Mar 2020 01:31

Publisher DOI:

10.1210/clinem/dgz232

PubMed ID:

31774122

Uncontrolled Keywords:

soluble α-Klotho; parathyroid hormone; phosphate

BORIS DOI:

10.7892/boris.135760

URI:

https://boris.unibe.ch/id/eprint/135760

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