Fibroblast growth factor 23-Klotho and hypertension: experimental and clinical mechanisms

Area of Science:

• Nephrology
• Pediatric Endocrinology
• Cardiovascular Medicine

Background:

• Hypertension (HTN) and chronic kidney disease (CKD) are rising concerns in pediatric populations, posing long-term cardiovascular risks.
• In CKD, increased sodium reabsorption elevates extracellular fluid volume, a primary driver of HTN.
• The renin-angiotensin-aldosterone system (RAAS) influences sodium transport, intersecting with the FGF23-Klotho axis and vitamin D metabolism.

Purpose of the Study:

• To review the intricate interplay between the FGF23-Klotho axis, vitamin D, and RAAS in pediatric hypertension associated with CKD.
• To elucidate how these systems contribute to blood pressure dysregulation in pediatric CKD.
• To discuss potential therapeutic strategies targeting these pathways for managing HTN in children with CKD.

Main Methods:

• Literature review focusing on the molecular and physiological interactions of FGF23, Klotho, vitamin D, and RAAS.
• Analysis of studies investigating the role of these factors in pediatric hypertension and CKD.
• Synthesis of current understanding of pathophysiological mechanisms and therapeutic approaches.

Main Results:

• The FGF23-Klotho axis modulates sodium transport and interacts with RAAS and vitamin D activation.
• FGF23 inhibits 1,25-dihydroxyvitamin D production, which normally suppresses renin synthesis.
• Disturbances in this axis contribute significantly to HTN pathophysiology in pediatric CKD.

Conclusions:

• Understanding the complex interactions of FGF23-Klotho, vitamin D, and RAAS is crucial for addressing pediatric hypertension in CKD.
• Therapeutic strategies targeting these interconnected systems hold promise for improving blood pressure control and cardiovascular outcomes in affected children.