How FGF23 shapes multiple organs in chronic kidney disease

Area of Science:

• Nephrology
• Pediatric Endocrinology
• Mineral Metabolism

Background:

• Chronic kidney disease (CKD) in children causes significant mineral metabolism disturbances, leading to CKD-mineral and bone disorder (CKD-MBD).
• CKD-MBD manifests as impaired bone mineralization, deformities, fractures, growth failure, muscle weakness, and vascular calcification.
• CKD-MBD is a primary driver of increased cardiovascular disease (CVD) comorbidity and mortality in pediatric patients.

Purpose of the Study:

• To review the regulators of fibroblast growth factor 23 (FGF23) synthesis altered in CKD.
• To summarize the main CKD-mediated organ dysfunctions associated with elevated FGF23 levels.

Main Methods:

• Review of existing clinical and experimental studies on FGF23 regulation and its effects in CKD.
• Analysis of the relationship between FGF23 levels and organ-specific complications in pediatric CKD.

Main Results:

• Elevated FGF23 is the earliest detectable mineral metabolism alteration in CKD-MBD.
• Increased FGF23 is linked to pathological cardiac remodeling, vascular alterations, and cognitive risks in pediatric CKD.
• FGF23's role in CKD-related hypertension and bone mineralization shows conflicting results, requiring further clarification.

Conclusions:

• FGF23 plays a central role in CKD-MBD pathogenesis and associated organ dysfunctions.
• Understanding FGF23 regulation and its downstream effects is crucial for managing pediatric CKD complications.
• Further research is needed to clarify causal relationships between FGF23 and specific CKD-mediated complications.