The relationship between serum α-Klotho with all-cause and cause-specific mortality

Q: What question does this study address about α-Klotho?

It tests whether serum α-Klotho protein levels are associated with all-cause and cause-specific mortality, noting that prior findings in humans have been inconsistent.

Q: How were the data and statistical models constructed?

The study used NHANES data from 2007 to 2016 and assessed non-linear (quadratic) associations with Cox proportional hazards models and competing risk models, adjusting for multiple confounders.

Q: What main relationship did the results show between α-Klotho and mortality?

The study found a U-shaped association between α-Klotho levels and all-cause mortality, and a similar U-shaped pattern for cancer mortality, while no relationship was observed for cardiovascular or other-cause mortality.

Sep 22, 2026

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Investigated whether serum α-Klotho (αK) protein levels relate to all-cause and cause-specific mortality in a large, diverse cohort representative of the US population. Analyzed NHANES data from 2007–2016, modeling non-linear (quadratic) associations using Cox proportional hazards and competing risk methods. Adjusted multivariable models accounted for demographics, comorbidities, lifestyle, body mass index, lipids, kidney function, education, and income. Results showed U-shaped risk patterns for all-cause and cancer mortality.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Klotho biology and α-Klotho functions

Epidemiological inconsistency and study rationale

DOI: 10.1111/bcp.16217 O R IG INA L ARTI CLE The relationship between serum α -Klotho with all-cause and cause-specific mortality Nargiza Sadr 1 | Cynthia J. Avila 2 | Hannah Chung 1 | Simrah Siddiqui 1 | Ayeman Basith 1 | Waleed Kassabo 1 | Rehan Qayyum 1 1Department of Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA 2EVMS School of Health Professions, Macon & Joan Brock Virginia Health Sciences, Old Domion University, Norfolk, Virginia, USA Correspondence Rehan Qayyum, MD, MHS, SFHM, FAHA, Department of Medicine, Eastern Virginia Medical School, 825 Fairfax Ave, Suite 571, Norfolk, VA 23507, USA. Email: [qayyumr@evms.edu](qayyumr@evms.edu) Funding information No funding was received for this study [Correction added on 12 November 2024, after first online publication: The article title has been corrected in this version.] Aims: The relationship between α-Klotho (α K) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum α K protein levels with all-cause and cause-specific mortality in a cohort representative of the US population. Methods: We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016 . A nonlinear association between mortality and αK levels asa quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio. Results: Of the 13 749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29 . 7 (6 . 7) kg/m2, and αK was 0 .85 (0 .31) ng/mL. In the adjusted Cox proportional hazards model with quadratic α K, we found a U-shaped relationship between all-cause mortality and α K levels (continuous α K hazard ratio [HR] = 0. 56, 95% confidence interval [CI]: 0 .37, 0 .85; P = .007; squared-αK HR = 1.25, 95% CI: 1 . 11, 1 .41; P < 0 .001) . A similar U-shaped relationship was noted between α K and cancer mortality in the adjusted Cox proportional hazards model (continuous αK HR = 0.45, 95% CI: 0 . 19, 1.06; P = 0.07; squared αK HR = 1.32, 95% CI: 1 .07, 1 . 61; P = 0.009) . No relationship was present with cardiovascular or other-cause mortality. Conclusions: In this large diverse cohort, we report a U-shaped relationship between αK with all-cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed. KEYWOR DS all-cause mortality, cancer mortality, cause-specific mortality, NHANES, α-Klotho This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s) . British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. 3278 SADR ET AL. 1 | INTRODUCTION Klotho is a multifunctional protein with three identified subtypes (α, β and γ) that collectively are involved in a vast network of biochemical mechanisms essential to survival.1–3 The most wellstudied subtype, α-Klotho (αK), has been shown to play a key role in nutrient metabolism, hormone regulation and ageing. 1,3,4 Klotho gene expression in the distal convoluted tubule of the kidney contributes to several pathophysiologic states including hypertension, kidney disease, adipogenesis, osteoporosis and cytokine production.2,5 αK is also known to play a key role in mineral homeostasis by regulating parathyroid hormone, vitamin D3, and serum phosphate levels, which ma

FAQs

What question does this study address about α-Klotho?

It tests whether serum α-Klotho protein levels are associated with all-cause and cause-specific mortality, noting that prior findings in humans have been inconsistent.

How were the data and statistical models constructed?

The study used NHANES data from 2007 to 2016 and assessed non-linear (quadratic) associations with Cox proportional hazards models and competing risk models, adjusting for multiple confounders.

What main relationship did the results show between α-Klotho and mortality?

The study found a U-shaped association between α-Klotho levels and all-cause mortality, and a similar U-shaped pattern for cancer mortality, while no relationship was observed for cardiovascular or other-cause mortality.

Sep 22, 2026

Upload by Evangeline