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.
Keywords: Alpha-klotho; Fibroblast growth factor 23; Habitual dietary acid load; Net acid excretion; Phosphate; Urinary potential renal acid load.
© 2024. The Author(s).