Phosphate and FGF-23.

Area of Science:

• Endocrinology
• Nephrology
• Mineral Metabolism

Background:

• Fibroblast growth factor (FGF)-23 is a key regulator of phosphate and calcitriol (1,25(OH)₂D₃) homeostasis.
• Osteocytes and osteoblasts secrete FGF-23 in response to phosphate loading or elevated calcitriol.
• In chronic kidney disease (CKD), FGF-23 is an early biomarker of impaired renal phosphate handling.

Purpose of the Study:

• To review the role of FGF-23 in CKD.
• To examine FGF-23's adaptive and maladaptive functions as CKD progresses.
• To discuss potential therapeutic strategies targeting FGF-23 in CKD.

Main Methods:

• Literature review of FGF-23's role in phosphate metabolism and CKD.
• Analysis of FGF-23's impact on renal phosphate excretion, calcitriol production, and parathyroid hormone (PTH) secretion.
• Examination of FGF-23 resistance in advanced CKD and its associated complications.

Main Results:

• Elevated FGF-23 levels in CKD increase phosphate excretion and decrease calcitriol, initially maintaining normophosphatemia.
• As CKD progresses, FGF-23 levels rise significantly, while responsiveness diminishes due to reduced Klotho expression.
• High FGF-23 in late CKD contributes to adverse outcomes like left ventricular hypertrophy, accelerated CKD progression, and mortality.

Conclusions:

• FGF-23 plays a critical adaptive role in early CKD but becomes detrimental in advanced stages.
• Therapeutic strategies aimed at lowering phosphate or modulating PTH may reduce FGF-23 levels in early CKD.
• Managing FGF-23 may offer a novel approach to improve patient outcomes in CKD.