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Klotho's Impact on Cardiovascular Disease, Fractures, and Mortality in Hemodialysis

Akio Nakashima1, Kazuhiko Kato1, Arisa Kobayashi1

  • 1Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Kidney International Reports
|October 27, 2025
PubMed

Insights

Low levels of soluble Klotho (sKlotho), an aging-suppressor protein, are linked to increased cardiovascular disease, fractures, and mortality in hemodialysis patients. This highlights sKlotho

Area of Science:

  • Nephrology and Gerontology
  • Biomarker Discovery
  • Cardiovascular and Skeletal Health

Background:

  • Klotho, an aging-suppressor protein, shows promise in animal models for improving cardiovascular and bone health in chronic kidney disease (CKD).
  • Clinical data on the role of soluble Klotho (sKlotho) in hemodialysis patients' outcomes remain limited.
  • Understanding sKlotho's association with clinical events is crucial for risk stratification in this population.

Purpose of the Study:

  • To investigate the association between serum sKlotho levels and cardiovascular disease (CVD) events.
  • To examine the relationship between sKlotho and fracture incidence.
  • To assess the link between sKlotho and all-cause mortality in patients undergoing hemodialysis.

Main Methods:

  • A cohort of 1241 hemodialysis patients was recruited from multiple institutions.
  • Patients were followed for a median of 39 months.
  • The primary composite outcome included CVD events, fractures, and all-cause mortality.

Main Results:

  • The median sKlotho concentration was 325.6 pg/ml.
  • Patients in the lowest quartile of sKlotho exhibited significantly higher risks for CVD events (HR=1.76), fractures (HR=1.99), and mortality (HR=1.74) compared to the highest quartile.
  • 436 CVD events, 100 fractures, and 228 deaths were recorded during follow-up.

Conclusions:

  • Low serum sKlotho levels are strongly associated with adverse cardiovascular and skeletal outcomes in hemodialysis patients.
  • Reduced sKlotho is a significant predictor of increased all-cause mortality in this population.
  • sKlotho may serve as a valuable biomarker for risk stratification among high-risk hemodialysis patients.
Abstract

Keywords:
FGF23Klothocardiovascular diseasefracturehemodialysis

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