[The couple fibroblast growth factor 23 (FGF23)/Klotho]

Area of Science:

• Endocrinology
• Nephrology
• Molecular Biology

Background:

• Fibroblast growth factor 23 (FGF23) is a bone-derived hormone regulating phosphate and calcitriol homeostasis.
• FGF23 exerts its functions by binding to a receptor complex involving FGF receptors and Klotho, primarily in the kidney and parathyroid glands.
• Klotho, a membrane-bound protein, can also be cleaved into a circulating form with an unknown function, but it may influence renal phosphate and calcium transporters.

Purpose of the Study:

• To investigate the roles of FGF23 and Klotho in phosphate and calcitriol regulation.
• To explore the relationship between FGF23, Klotho, and the development of secondary hyperparathyroidism in renal insufficiency.
• To examine the association of FGF23 and Klotho levels with mortality and cardiac complications in chronic kidney disease.

Main Methods:

• Analysis of FGF23 and Klotho expression and function in vivo using gene-disruption mouse models.
• Measurement of plasma FGF23 and Klotho concentrations in animal models and human subjects with renal insufficiency.
• Correlation analysis to assess the relationship between FGF23, Klotho, mortality, and cardiac parameters.

Main Results:

• FGF23 and Klotho gene disruption in mice results in distinct but related phenotypes concerning FGF23 levels.
• In renal insufficiency, FGF23 plasma levels increase, while Klotho production decreases, contributing to secondary hyperparathyroidism.
• Elevated FGF23 and diminished Klotho levels are significantly associated with increased mortality, particularly from cardiovascular causes, and cardiac dysfunction.

Conclusions:

• FGF23 and Klotho play critical roles in mineral metabolism and are implicated in the pathophysiology of chronic kidney disease.
• The interplay between FGF23 and Klotho is crucial in managing phosphate levels and preventing hyperparathyroidism.
• Altered FGF23 and Klotho levels represent significant risk factors for cardiovascular complications and mortality in patients with kidney disease.