Fibroblast Growth Factor-23 and Cardiovascular Disease in Patients With Chronic Kidney Disease

Area of Science:

• Nephrology
• Cardiology
• Endocrinology

Background:

• Chronic kidney disease (CKD) significantly increases cardiovascular morbidity and mortality risk beyond traditional factors.
• Fibroblast growth factor-23 (FGF-23), a bone-derived hormone, rises early in CKD and mediates cardiorenal-osteoendocrine dysfunction.
• Pathological FGF-23 signaling in CKD promotes cardiac hypertrophy, fibrosis, and dysfunction via Klotho-independent pathways.

Purpose of the Study:

• To review the physiology of FGF-23 and its pathological role in CKD-associated cardiac disease.
• To examine the clinical evidence supporting FGF-23 as a cardiovascular risk biomarker.
• To discuss current and emerging therapeutic strategies targeting the FGF-23-Klotho-FGFR axis.

Main Methods:

• Review of existing literature on FGF-23, CKD, and cardiovascular outcomes.
• Analysis of cohort studies demonstrating FGF-23's predictive value for cardiac events.
• Examination of mechanistic studies on FGF-23's cardiac signaling pathways.

Main Results:

• Elevated FGF-23 independently predicts left ventricular hypertrophy, heart failure, atrial fibrillation, and mortality in CKD and non-CKD populations.
• FGF-23 acts as a biomarker for cardiovascular risk, particularly in heart failure with preserved ejection fraction.
• Clinical use is limited by assay variability and lack of outcome-proven interventions.

Conclusions:

• FGF-23 is a critical mediator linking CKD to cardiovascular complications.
• Targeting the FGF-23-Klotho-FGFR axis represents a potential therapeutic strategy for cardiorenal protection.
• Further research is needed to standardize FGF-23 assessment and validate therapeutic interventions.