The role of fibroblast growth factor 23 and Klotho in uremic cardiomyopathy

Area of Science:

• Nephrology
• Cardiology
• Endocrinology

Background:

• Chronic kidney disease (CKD) is linked to cardiac hypertrophy through various systemic factors like hypertension and inflammation.
• Phosphate metabolism disturbances are emerging as key nonclassical risk factors for cardiovascular mortality in CKD patients.
• Altered levels and activity of phosphate regulators contribute to cardiac hypertrophy as kidney function declines.

Purpose of the Study:

• To review the direct and indirect effects of fibroblast growth factor 23 (FGF23) and soluble Klotho on cardiac remodeling in CKD.
• To explore the novel pathomechanisms of cardiac hypertrophy involving FGF23 and Klotho in CKD.
• To discuss the crosstalk between FGF23 and Klotho in regulating cardiac hypertrophy.

Main Methods:

• Review of recent findings on FGF23 and Klotho in CKD-related cardiac remodeling.
• Analysis of studies investigating the direct cardiac effects of FGF23 and Klotho.
• Examination of the interplay between FGF23, Klotho, and cardiac hypertrophy.

Main Results:

• FGF23 directly induces cardiac hypertrophy in myocytes via FGF receptor 4, independent of blood pressure.
• Soluble Klotho may offer direct myocardial protection against CKD-associated stress, including uremic toxins and FGF23.
• Elevated FGF23 and reduced soluble Klotho synergistically promote uremic cardiomyopathy.

Conclusions:

• FGF23 and Klotho represent a novel pathway contributing to cardiac hypertrophy in CKD.
• The balance between FGF23 and Klotho is critical for preventing uremic cardiomyopathy.
• Targeting the FGF23-Klotho axis may offer therapeutic strategies for cardiovascular complications in CKD.