Fibroblast Growth Factor-23-A Potential Uremic Toxin

Area of Science:

• Endocrinology
• Nephrology
• Cardiovascular Medicine

Background:

• Fibroblast growth factor-23 (FGF23) is a hormone primarily produced by osteocytes and osteoblasts.
• FGF23 regulates phosphate and vitamin D metabolism, lowering serum phosphate by reducing kidney reabsorption and 1,25(OH)₂-D generation.
• Elevated FGF23 is an early hallmark of chronic kidney disease (CKD), initially compensatory but leading to target organ toxicity.

Purpose of the Study:

• To review the role of FGF23 in CKD pathogenesis and clinical outcomes.
• To discuss factors influencing FGF23 levels and potential therapeutic strategies.
• To highlight kidney transplantation as the optimal method for FGF23 normalization in dialysis patients.

Main Methods:

• Review of clinical studies and existing literature on FGF23 in CKD.
• Analysis of FGF23's impact on renal, cardiovascular, and mortality outcomes.
• Examination of factors that increase or decrease FGF23 levels and emerging therapies.

Main Results:

• High plasma FGF23 is independently linked to CKD progression, cardiovascular complications, and mortality.
• FGF23 contributes to cardiomyocyte hypertrophy, vascular calcification, and endothelial dysfunction via the PLCγ-calcineurin-NFAT pathway.
• Factors increasing FGF23 include active vitamin D, inflammation, and iron deficiency; factors decreasing it include phosphate restriction, phosphate binders, cinacalcet, and nicotinamide.

Conclusions:

• Elevated FGF23 is a significant risk factor in CKD, contributing to adverse outcomes.
• While various interventions can modulate FGF23, kidney transplantation offers the most effective normalization in maintenance hemodialysis patients.
• Targeting FGF23 and its pathways remains a critical area for therapeutic development in CKD management.