Fibroblast growth factor 23--structure, function and role in kidney diseases

Area of Science:

• Endocrinology
• Nephrology
• Mineral Metabolism

Background:

• Fibroblast growth factor-23 (FGF-23) is a key hormone regulating phosphate and vitamin D metabolism.
• Produced by bone cells, FGF-23 acts on the kidneys to inhibit phosphate reabsorption and calcitriol synthesis.
• Imbalances in FGF-23 are linked to conditions like rickets, osteomalacia, and tissue calcinosis.

Purpose of the Study:

• To review the role of FGF-23 in phosphate homeostasis and its implications in chronic kidney disease (CKD).
• To discuss the dual role of FGF-23 in early CKD as a protective mechanism and a potential contributor to complications.
• To explore the association between FGF-23 levels and mortality in CKD patients.

Main Methods:

• Literature review of studies on FGF-23, phosphate metabolism, and CKD.
• Analysis of circulating forms of FGF-23 (intact and C-terminal).
• Examination of FGF-23 regulation, stimuli, and biological actions.

Main Results:

• FGF-23 levels, both intact (iFGF-23) and C-terminal (cFGF-23), rise in early CKD (stages 2-3).
• Increased FGF-23 secretion in early CKD may be a compensatory response to prevent phosphate accumulation.
• Elevated FGF-23 is associated with calcitriol deficiency, secondary hyperparathyroidism, and increased mortality in CKD.

Conclusions:

• FGF-23 plays a critical role in mineral metabolism, with altered levels indicating disease states.
• While initially protective in CKD, persistently high FGF-23 may contribute to adverse outcomes.
• Further research is needed to clarify the direct toxicity of FGF-23 versus its role as a marker of disease severity.