Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 21;20(7):922-930.
doi: 10.2215/CJN.0000000722.

Unveiling the Causal Relationship between Thyroid and Kidney Function: A Multivariable Mendelian Randomization

Hsiao-Mei Tsao  1   2   3   4 , Yu-Hsuan Joni Shao  3   4 , Yi-Cheng Chang  5   6   7 , Yu-Hsiang Chou  1   2 , Vin-Cent Wu  1   2 , Shuei-Liong Lin  1   8 , Yung-Ming Chen  2   9 , Tai-Shuan Lai  1   2
Affiliations

Unveiling the Causal Relationship between Thyroid and Kidney Function: A Multivariable Mendelian Randomization

Hsiao-Mei Tsao et al. Clin J Am Soc Nephrol. .

Abstract

Key Points:

  1. Thyroid-stimulating hormone levels were inversely associated with eGFR, and hypothyroidism was correlated with lower eGFR levels.

  2. Multivariable Mendelian randomization analysis confirms a causal link between elevated thyroid-stimulating hormone levels and reduced eGFR in diverse populations.

  3. Findings highlight the importance of considering thyroid dysfunction in CKD management and targeted treatments.

Background: Recent studies suggest an association between thyroid dysfunction and kidney function, but the causal relationship remains uncertain. The complex interactions between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and thyroid peroxidase antibodies (TPOAb) complicate the assessment of this link. This study employed multivariable Mendelian randomization (MVMR) to elucidate the causal relationship between thyroid dysfunction and kidney function in East Asian and European populations.

Methods: We conducted a cross-sectional study and MVMR analysis using data from 17,733 participants in the Taiwan Biobank. Thyroid function was assessed by measuring TSH, fT4 and TPOAb levels, with hypothyroidism classified as subclinical or overt. The primary outcome was creatinine-based eGFR, calculated using the CKD Epidemiology Collaboration equation. Observational analyses were adjusted for age, sex, body mass index, and metabolic and cardiovascular factors. MVMR analyses used genetic variants associated with TSH, fT4, and TPOAb levels to assess their causal effects on eGFR. Data from the ThyroidOmics and CKD Genetics Consortium were used to replicate findings in European populations.

Results: Both TSH and fT4 levels were inversely associated with eGFR, and hypothyroidism was correlated with lower eGFR. Conversely, TPOAb was positively associated with eGFR. Mendelian randomization analyses, using 26 genetic variants for TSH, four for fT4, and eight for TPOAb confirmed a causal relationship between TSH and eGFR. Significant causal effects of TSH were observed across various MVMR methods (P values from <0.001 to 0.01), whereas fT4 and TPOAb showed no significant causal effects (both P > 0.05). These findings were consistent in European populations.

Conclusions: The study found that elevated TSH levels are causally associated with reduced kidney function, highlighting the potential importance of thyroid function in kidney health. These findings suggest that thyroid dysfunction should be considered in managing patients with CKD.

Keywords: CKD; clinical epidemiology; epidemiology and outcomes; longitudinal data analysis; metabolism; risk factors.

PubMed Disclaimer

Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/CJN/C262.

References

    1. Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V. Chronic kidney disease. Lancet. 2021;398(10302):786–802. doi: 10.1016/S0140-6736(21)00519-5 - DOI - PubMed
    1. Carney EF. The impact of chronic kidney disease on global health. Nat Rev Nephrol. 2020;16(5):251. doi: 10.1038/s41581-020-0268-7 - DOI - PubMed
    1. Ricardo AC Yang W Sha D, et al. Sex-related disparities in CKD progression. J Am Soc Nephrol. 2019;30(1):137–146. doi: 10.1681/ASN.2018030296 - DOI - PMC - PubMed
    1. Bansal N Xie D Tao K, et al. Atrial fibrillation and risk of ESRD in adults with CKD. Clin J Am Soc Nephrol. 2016;11(7):1189–1196. doi: 10.2215/CJN.10921015 - DOI - PMC - PubMed
    1. Rahman M Xie D Feldman HI, et al. Association between chronic kidney disease progression and cardiovascular disease: results from the CRIC study. Am J Nephrol. 2014;40(5):399–407. doi: 10.1159/000368915 - DOI - PMC - PubMed

LinkOut - more resources