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Updated: Jul 9, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Klotho and lean mass as novel cardiovascular risk factors in hemodialysis patients
Ana Rita Martins1,2, Sofia Azeredo-Lopes3,4, Sofia Azeredo Pereira5,6
1Nephrology Department, Hospital Santa Cruz, Western Lisbon Hospital Centre, Lisbon, Portugal.
Insights
Alpha-Klotho and lean mass are novel cardiovascular risk factors in hemodialysis patients. Higher alpha-Klotho and lean mass levels are associated with reduced mortality risk, while ADMA is linked to peripheral vascular disease.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Patients with chronic kidney disease (CKD) face elevated cardiovascular (CV) risks.
- Traditional CV risk factors are well-established, but novel factors like α-Klotho, ADMA, and lean mass require further investigation.
Purpose of the Study:
- To evaluate the association between α-Klotho, ADMA, and lean mass with the risk of peripheral vascular disease (PVD), CV events, and all-cause mortality.
- To identify novel CV risk factors in patients undergoing hemodialysis.
Main Methods:
- Observational, prospective, single-center cohort study.
- Included 200 adult patients on hemodialysis (online hemodiafiltration).
- Utilized logistic regression, Cox proportional hazards models, and Kaplan-Meier analysis.
Main Results:
- Increased α-Klotho levels correlated with decreased odds of PVD and CV events.
- Increased ADMA levels were significantly associated with increased odds of PVD.
- Higher α-Klotho and lean mass levels were associated with reduced risk of all-cause mortality, independent of confounders.
Conclusions:
- α-Klotho and lean mass emerge as significant novel predictors of reduced all-cause mortality in hemodialysis patients.
- These findings support α-Klotho and lean mass as important factors in managing cardiovascular risk in CKD patients.
Background:
Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass.
Methods:
This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan-Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients.
Results:
A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270-0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203-0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055-41.606, P < .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140-0.906, P < .05) and lean mass (HR 0.187, 95% CI 0.042-0.829, P < .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables.
Conclusions:
Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.
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