Young Adults' Circulating FGF23 and α-klotho and Their Relationship with Habitual Dietary Acid Load and Phosphorus Intake During Growth

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 13

PMID 39537770

Authors

Luciana Peixoto Franco

Seyedeh-Masomeh Derakhshandeh-Rishehri

Ute Nothlings

Michaela F Hartmann

Christian Herder

Hermann Kalhoff

Stefan A Wudy

Thomas Remer

Affiliations

Soon will be listed here.

Abstract

The bone-derived hormone FGF23, primarily secreted by osteocytes, is a major player in the regulation of phosphate homeostasis. It becomes upregulated by increased circulating phosphate concentration, e.g. due to elevations in phosphorus intake (P-In) or alterations in habitual dietary acid load. The present study aimed to investigate whether long-term endogenous acid production or a habitual high phosphorus intake during childhood and adolescence may be prospectively related with altered adult levels of FGF23 and the FGF23-related metabolite α-klotho. Urinary phosphate excretion (PO4-Ex), net acid excretion (NAE), and potential renal acid load (uPRAL) were analyzed in 24-h urine samples (n = 3369) collected from 343 healthy 3-17 years old participants of the DONALD Study (Dortmund, Germany) to assess, biomarker-based, P-In and habitual dietary acid load. Circulating FGF23, α-klotho, and further blood parameters were additionally examined in young adulthood. Individual means of standard-deviation-scores were calculated for 24-h urinary biomarker excretions and anthropometrics longitudinally determined between ages 3-17 years. Multivariable linear regression was used to analyze the prospective relations of pre-adulthood PO4-Ex, NAE, and uPRAL with the adulthood outcomes FGF23 and α-klotho. After adjusting for growth period-related covariates and adulthood confounders only for P-In during growth, i.e., PO4-Ex, but not for NAE and uPRAL, a significant positive association (p = 0.03) with FGF23 and an inverse trend (p = 0.10) with the FGF23-α-klotho ratio were observed. Neither PO4-Ex, nor NAE or uPRAL were associated with soluble α-klotho levels in adulthood. The prospective relationships of long-term assessed 24-h phosphaturia and habitual dietary acid load during growth with adult circulating, phosphate-adjusted FGF23 strongly suggest that children´s habitually higher P-In does unfavorably affect adult FGF23-α-klotho axis.

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