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

TL;DR

Low levels of the Klotho protein are linked to higher risks of heart disease, fractures, and death in patients on hemodialysis.

Contribution

This study is the first to show a clinical association between soluble Klotho levels and adverse outcomes in hemodialysis patients.

Findings

Low sKlotho levels are associated with increased cardiovascular events in hemodialysis patients.

Patients with the lowest sKlotho levels had a higher risk of fractures and mortality.

sKlotho may serve as a biomarker for risk stratification in hemodialysis populations.

Abstract

Klotho, an aging-suppressor protein, has been shown to promote cardiovascular and bone health in animal models of chronic kidney disease (CKD). However, limited data exist on its role in clinical outcomes among patients undergoing hemodialysis. This study aimed to investigate the association between soluble Klotho (sKlotho) levels and cardiovascular disease (CVD) events, fractures, and all-cause mortality in this population.

We enrolled 1241 patients on hemodialysis from multiple medical institutions, with a median follow-up of 39 months. The primary outcome was a composite of CVD events, fractures, and all-cause mortality.

The median sKlotho concentration was 325.6 pg/ml (interquartile range [IQR]: 248.9–434.4 pg/ml). During the follow-up, 436 CVD and 100 fracture events were recorded, along with 228 deaths. Patients in the lowest quartile of sKlotho had significantly higher risks of CVD events (hazard ratio [HR] = 1.76; 95% confidence interval [CI]: 1.20–2.60), fractures (HR = 1.99; 95% CI: 1.01–3.91) and mortality (HR = 1.74; 95% CI: 1.00–3.03) than those in the highest quartile.

These findings suggest that low serum sKlotho levels are strongly associated with poor cardiovascular and skeletal outcomes and increased mortality in patients on hemodialysis. This study highlights the potential utility of sKlotho as a biomarker for risk stratification in this high-risk population.

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