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Assessment of Vascular Function in Patients With Chronic Kidney Disease
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Assessment of Vascular Function in Patients With Chronic Kidney Disease

Published on: June 16, 2014

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FGF23 and klotho at the intersection of kidney and cardiovascular disease

Daniel Edmonston1,2, Alexander Grabner1, Myles Wolf3,4

  • 1Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.

Nature Reviews. Cardiology
|July 14, 2023
PubMed

Insights

Cardiovascular disease is a major risk in chronic kidney disease (CKD). In CKD, fibroblast growth factor 23 (FGF23) and low klotho contribute to heart problems, necessitating holistic treatment of mineral imbalances.

Area of Science:

  • Nephrology
  • Cardiology
  • Endocrinology

Background:

  • Cardiovascular disease (CVD) is the primary cause of mortality in chronic kidney disease (CKD) patients.
  • CKD progression exacerbates CVD risk through CKD-specific factors like disordered mineral homeostasis.
  • Fibroblast growth factor 23 (FGF23) and klotho are key regulators of mineral balance, impacting cardiovascular health.

Purpose of the Study:

  • To explore the role of FGF23 and klotho in cardiovascular complications of CKD.
  • To investigate the mechanisms by which FGF23 excess and klotho deficiency promote cardiac dysfunction.
  • To evaluate the potential of targeting mineral homeostasis for improving cardiovascular outcomes in CKD.

Main Methods:

  • Review of emerging data on FGF23 and klotho in CKD-associated cardiovascular disease.
  • Analysis of the interplay between FGF23, klotho, and mineral metabolism.
  • Discussion of the clinical implications for managing cardiovascular risk in CKD.

Main Results:

  • Rising FGF23 and declining klotho in CKD lead to klotho-independent, detrimental cardiac effects, including left ventricular hypertrophy and heart failure.
  • Soluble klotho may offer protective cardiovascular benefits through various mechanisms.
  • The complex feedback loops between FGF23 and klotho make it challenging to isolate the primary driver of pathology.

Conclusions:

  • Targeting disordered mineral homeostasis holistically is crucial for improving cardiovascular outcomes in CKD patients.
  • Randomized trials should focus on practical interventions addressing mineral imbalances.
  • Further research is needed to fully elucidate the specific roles of FGF23 and klotho in distinct cardiovascular complications of CKD.

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