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. 2025 Mar;57(3):939-946.
doi: 10.1007/s11255-024-04262-8. Epub 2024 Nov 2.

Uric acid mediates the association between testosterone and α-Klotho among males: results from the NHANES 2013-2016

Andong Guo  1 , Jishuang Cao  2 , Chenrui Wu  2 , Sentai Ding  3   4
Affiliations

Uric acid mediates the association between testosterone and α-Klotho among males: results from the NHANES 2013-2016

Andong Guo et al. Int Urol Nephrol. 2025 Mar.

Abstract

Purpose: This study initially conducted a cross-sectional analysis to examine the association between total testosterone (TT), uric acid, and Klotho. The investigation examined whether uric acid mediates the association between TT and Klotho in males.

Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016, this study performed weighted multivariable-adjusted linear regression to evaluate the association between TT, uric acid, and α-Klotho. Then, mediation analysis was conducted to delineate the potential mediating role of uric acid in the TT-Klotho association.

Results: Multivariable linear regression analyses revealed inverse relationships between TT and uric acid (β = - 2.75, 95% CI: - 4.21, 1.28, p < 0.001) and between uric acid and α-Klotho (β = - 4.80, 95% CI: - 6.47, - 3.13, p < 0.001). Conversely, a positive correlation existed between TT and α-Klotho (β = 5.38, 95% CI: 2.23, 8.53, p < 0.001). Updated subgroup analyses show that the association strength between α-Klotho, TT, and uric acid levels was consistent across various population settings without significant variations. Restricted cubic spline analysis identified a non-linear association between TT and uric acid with an inflection point at 201 ng/mL. Mediation analysis confirmed uric acid-mediated 18.59% of the association between TT and α-Klotho (p < 0.001), highlighting its significant intermediary role.

Conclusion: This study elucidates the complex interrelationship between TT, uric acid, and α-Klotho, highlighting uric acid's significant mediating role. These findings provide novel insights into the hormonal and metabolic mechanisms underlying age-related processes and longevity.

Keywords: Mediation analysis; NHANES; Testosterone; Uric acid; α-Klotho.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no conflict oif interests. Informed consent: Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Institutional review board statement: The NHANES survey protocol was approved by the NCHS Research Ethics Review Committee ( https://www.cdc.gov/nchs/nhanes/irba98.htm ), and informed written consent was obtained from all participants. Since the NHANES database is publicly accessible, this study was exempt from further ethical review.

References

    1. Vingren JL, Kraemer WJ, Ratamess NA et al (2010) Testosterone physiology in resistance exercise and training: the up-stream regulatory elements. Sports Med 40:1037–1053 - DOI - PubMed
    1. Miller WL (1988) Molecular biology of steroid hormone synthesis. Endocr Rev 9:295–318 - DOI - PubMed
    1. Halpern JA, Brannigan RE (2019) Testosterone deficiency. JAMA 322:1116 - DOI - PubMed
    1. Andropause BJ (2001) Testosterone replacement therapy for aging men. Can Fam Phys 47:91–97
    1. Hazzard WR (1989) Why do women live longer than men? Biologic differences that influence longevity. Postgrad Med 85(271–278):281–273

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