Skip to main content

Advertisement

SpringerLink
Log in

J-shaped association of free triiodothyronine to free thyroxine ratio with 5-year mortality among patients with chronic kidney disease: a prospective cohort study

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association of free triiodothyronine to free thyroxine (FT3/FT4) ratio with 5-year mortality in patients with chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) through 2001–2002 and 2007–2012.

Methods

Two thousand four hundred twenty-four patients with CKD stage 1–5 were included. Patients’ baseline characteristics were collected. Cox proportional hazards models were used to investigate the association of FT3/FT4 ratio with 5-year all-cause and cardiovascular mortality. Subgroup analysis was performed.

Results

Within 5 years of follow-up duration, 425 (17.53%) deaths were recorded, and 154 patients died from cardiovascular disease. A J-shaped association between FT3/FT4 ratio and 5-year mortality was observed. After fully adjustment, the elevated FT3/FT4 ratio was significantly associated with a decreased 5-year all-cause mortality risk (HR: 0.79, 95% CI 0.63–0.99) among patients with CKD stage 1–5 when FT3/FT4 ratio < 4.71, and is significantly associated with an increased 5-year all-cause mortality risk in CKD patients with advanced CKD stages or low UACR when FT3/FT4 ratio ≥ 4.71 (HR: 2.74, 95% CI 1.20–6.29; HR: 3.09, 95% CI 1.12–8.57, respectively). The elevated FT3/FT4 ratio also showed a J-shaped association with the 5-year cardiovascular mortality which disappears after fully adjustment.

Conclusion

The FT3/FT4 ratio is closely associated with 5-year mortality risk among patients with CKD, indicating a potential role of FT3/FT4 ratio as a biomarker for mortality prediction in CKD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Availability of data and materials

All data used in the study are publicly available online. (https://wwwn.cdc.gov/nchs/nhanes/Default.aspx and https://www.cdc.gov/nchs/data-linkage/mortality-public.htm).

References

  1. Kalantar-Zadeh K et al (2021) Chronic kidney disease. Lancet 398(10302):786–802. https://doi.org/10.1016/S0140-6736(21)00519-5

    Article  CAS  PubMed  Google Scholar 

  2. Levey AS et al (2005) Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67(6):2089–2100. https://doi.org/10.1111/j.1523-1755.2005.00365.x

    Article  PubMed  Google Scholar 

  3. Jankowski J et al (2021) Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options. Circulation 143(11):1157–1172. https://doi.org/10.1161/CIRCULATIONAHA.120.050686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fraser SDS et al (2017) The association of serum free light chains with mortality and progression to end-stage renal disease in chronic kidney disease: systematic review and individual patient data meta-analysis. Mayo Clin Proc 92(11):1671–1681. https://doi.org/10.1016/j.mayocp.2017.08.021

    Article  CAS  PubMed  Google Scholar 

  5. Sun J et al (2016) Biomarkers of cardiovascular disease and mortality risk in patients with advanced CKD. Clin J Am Soc Nephrol 11(7):1163–1172. https://doi.org/10.2215/CJN.10441015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fassett RG et al (2011) Biomarkers in chronic kidney disease: a review. Kidney Int 80(8):806–821. https://doi.org/10.1038/ki.2011.198

    Article  CAS  PubMed  Google Scholar 

  7. Kaptein EM (1996) Thyroid hormone metabolism and thyroid diseases in chronic renal failure. Endocr Rev 17(1):45–63. https://doi.org/10.1210/edrv-17-1-45

    Article  CAS  PubMed  Google Scholar 

  8. Lo JC et al (2005) Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int 67(3):1047–1052. https://doi.org/10.1111/j.1523-1755.2005.00169.x

    Article  PubMed  Google Scholar 

  9. Chonchol M et al (2008) Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Soc Nephrol 3(5):1296–1300. https://doi.org/10.2215/CJN.00800208

    Article  PubMed  PubMed Central  Google Scholar 

  10. Xu G, Yan W, Li J (2014) An update for the controversies and hypotheses of regulating nonthyroidal illness syndrome in chronic kidney diseases. Clin Exp Nephrol 18(6):837–843. https://doi.org/10.1007/s10157-014-0974-1

    Article  CAS  PubMed  Google Scholar 

  11. Fan J et al (2016) Prevalence and clinical significance of low T3 syndrome in non-dialysis patients with chronic kidney disease. Med Sci Monit 22:1171–1179. https://doi.org/10.12659/msm.895953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xu LC et al (2021) The correlation between low serum T3 levels and all-cause and cardiovascular mortality in peritoneal dialysis patients. Ther Clin Risk Manag 17:851–861. https://doi.org/10.2147/TCRM.S324672

    Article  PubMed  PubMed Central  Google Scholar 

  13. Drechsler C et al (2014) Thyroid function, cardiovascular events, and mortality in diabetic hemodialysis patients. Am J Kidney Dis 63(6):988–996. https://doi.org/10.1053/j.ajkd.2013.10.009

    Article  CAS  PubMed  Google Scholar 

  14. Schultheiss UT et al (2021) Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study. Clin Kidney J 14(3):959–968. https://doi.org/10.1093/ckj/sfaa052

    Article  CAS  PubMed  Google Scholar 

  15. Shimizu Y et al (2022) Associations among Ratio of Free Triiodothyronine to Free Thyroxine, Chronic Kidney Disease, and Subclinical Hypothyroidism. J Clin Med. https://doi.org/10.3390/jcm11051269

    Article  PubMed  PubMed Central  Google Scholar 

  16. Inaba M et al (2021) Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients. Nutrients. https://doi.org/10.3390/nu13124537

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang L et al (2022) The serum free triiodothyronine to free thyroxine ratio as a potential prognostic biomarker of chronic kidney disease in patients with glomerular crescents: a retrospective study. Front Endocrinol (Lausanne) 13:977355. https://doi.org/10.3389/fendo.2022.977355

    Article  PubMed  Google Scholar 

  18. Chen TC et al (2018) National health and nutrition examination survey: estimation procedures, 2011–2014. Vital Health Stat 2 177:1–26

    Google Scholar 

  19. Miller WG et al (2022) National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories. Clin Chem 68(4):511–520. https://doi.org/10.1093/clinchem/hvab278

    Article  PubMed  Google Scholar 

  20. Murphy D et al (2016) Trends in prevalence of chronic kidney disease in the United States. Ann Intern Med 165(7):473–481. https://doi.org/10.7326/M16-0273

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhang NH et al (2020) Leisure-time physical activity and mortality in CKD: a 1999–2012 NHANES analysis. Am J Nephrol 51(11):919–929. https://doi.org/10.1159/000511685

    Article  PubMed  Google Scholar 

  22. Kim D et al (2021) Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States. J Hepatol 75(6):1284–1291. https://doi.org/10.1016/j.jhep.2021.07.035

    Article  CAS  PubMed  Google Scholar 

  23. Ataoglu HE et al (2018) Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome. Eur J Intern Med 57:91–95. https://doi.org/10.1016/j.ejim.2018.07.018

    Article  CAS  PubMed  Google Scholar 

  24. Yang JW et al (2012) Serum T3 level can predict cardiovascular events and all-cause mortality rates in CKD patients with proteinuria. Ren Fail 34(3):364–372. https://doi.org/10.3109/0886022X.2011.647342

    Article  CAS  PubMed  Google Scholar 

  25. Rhee CM (2015) Low-T3 syndrome in peritoneal dialysis: metabolic adaptation, marker of illness, or mortality mediator? Clin J Am Soc Nephrol 10(6):917–919. https://doi.org/10.2215/CJN.04310415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li J et al (2020) Association of Serum Thyroid Hormones with the Risk and Severity of Chronic Kidney Disease Among 3563 Chinese Adults. Med Sci Monit 26:e922910. https://doi.org/10.1265/MSM.922910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lang X et al (2022) FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007–2012. Front Endocrinol (Lausanne) 13:964822. https://doi.org/10.3389/fendo.2022.964822

    Article  PubMed  Google Scholar 

  28. Kozdag G et al (2005) Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur J Heart Fail 7(1):113–118. https://doi.org/10.1016/j.ejheart.2004.04.016

    Article  CAS  PubMed  Google Scholar 

  29. Neves JS et al (2019) Lower free triiodothyronine levels within the reference range are associated with higher cardiovascular mortality: an analysis of the NHANES. Int J Cardiol 285:115–120. https://doi.org/10.1016/j.ijcard.2019.03.009

    Article  PubMed  Google Scholar 

  30. Yuan D et al (2021) Usefulness of FT3 to FT4 ratio to predict mortality in euthyroid patients with prior cardiovascular events undergoing PCI: five-year findings from a large single-center cohort study. Front Endocrinol (Lausanne) 12:700349. https://doi.org/10.3389/fendo.2021.700349

    Article  PubMed  Google Scholar 

  31. Wang C et al (2022) Value of FT3/FT4 ratio in prognosis of patients with heart failure: a propensity-matched study. Front Cardiovasc Med 9:859608. https://doi.org/10.3389/fcvm.2022.859608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hong J et al (2022) Free triiodothyronine and free triiodothyronine to free thyroxine ratio predict all-cause mortality in patients with diabetic foot ulcers. Diabetes Metab Syndr Obes 15:467–476. https://doi.org/10.2147/DMSO.S354754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. He X et al (2022) Low FT3/FT4 ratio is linked to poor prognosis of acute myocardial infarction in euthyroid patients with type 2 diabetes mellitus. J Clin Med. https://doi.org/10.3390/jcm11216530

    Article  PubMed  PubMed Central  Google Scholar 

  34. Schirripa M et al (2018) Prognostic value of thyroid hormone ratios in patients with advanced metastatic colorectal cancer treated with regorafenib: the TOREADOR study. Clin Colorectal Cancer 17(3):e601–e615. https://doi.org/10.1016/j.clcc.2018.05.013

    Article  PubMed  Google Scholar 

  35. Yuan D et al (2021) Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr Metab Cardiovasc Dis 31(2):579–586. https://doi.org/10.1016/j.numecd.2020.10.011

    Article  CAS  PubMed  Google Scholar 

  36. Kong SH et al (2020) Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population. Osteoporos Int 31(3):525–531. https://doi.org/10.1007/s00198-019-05137-w

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank participants and staff of the NHANES.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82200813), and the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University.

Author information

Authors and Affiliations

  1. Department of Nephrology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, 410011, China

    Siyao Li & Mengru Zeng

Authors
  1. Siyao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mengru Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SL and MZ designed the study. SL analyzed and interpreted the data. SL drafted the manuscript. MZ revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mengru Zeng.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The studies involving human participants were reviewed and approved by The National Center for Health Statistics Research Ethics Review Board. The patients/participants provided their written informed consent to participate in this study.

Informed consent

All participants provided written informed consent in the NHANES.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, S., Zeng, M. J-shaped association of free triiodothyronine to free thyroxine ratio with 5-year mortality among patients with chronic kidney disease: a prospective cohort study. Int Urol Nephrol 55, 2567–2578 (2023). https://doi.org/10.1007/s11255-023-03548-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-023-03548-7

Keywords

Search

Navigation