Skip to main content

Advertisement

SpringerLink
Log in

Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Aim

Non-thyroidal illness syndrome (NTIS) is common among patients with advanced chronic kidney disease (CKD) and is strongly associated with poor prognosis. However, it remains unclear in how to correct this disorder and this study aimed to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine (NAC) for correcting NTIS status.

Methods

Patients with CKD stage 3–4 were single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks. The primary end points were the correction of NTIS and the occurrence of end-stage renal disease (ESRD). The secondary point was the change in estimated glomerular filtration rate (eGFR) after the follow-up.

Results

The Kaplan–Meier survival analysis showed significant lower correcting ratio of NTIS in control group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval (CI) 0.04–0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02–0.38, p = 0.001), and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02–3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23–13.57, p < 0.001). The Cox regression analysis demonstrated significantly different effectiveness of placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively. Variance analysis displayed a greater reduction in eGFR in controls than in SB (p = 0.044) and NAC group (p < 0.001).

Conclusion

SB and NAC are effective in promoting the recovery from NTIS status and delaying the deterioration of renal function in advanced 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

Similar content being viewed by others

References

  1. Docter R, Krenning EP, de Jong M, Hennemann G (1993) The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism. Clin Endocrinol (Oxf) 39(5):499–518

    Article  CAS  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. Lim VS, Fang VS, Katz AI, Refetoff S (1977) Thyroid dysfunction in chronic renal failure. A study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine. J Clin Invest 60(3):522–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lo JC, Chertow GM, Go AS, Hsu CY (2005) Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int 67(3):1047–1052

    Article  PubMed  Google Scholar 

  5. De Groot LJ (1999) Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab 84(1):151–164

    Article  PubMed  Google Scholar 

  6. Van den Berghe G (2014) Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid 24(10):1456–1465

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bacci V, Schussler GC, Kaplan TB (1982) The relationship between serum triiodothyronine and thyrotropin during systemic illness. J Clin Endocrinol Metab 54(6):1229–1235

    Article  CAS  PubMed  Google Scholar 

  8. McIver B, Gorman CA (1997) Euthyroid sick syndrome: an overview. Thyroid 7(1):125–132

    Article  CAS  PubMed  Google Scholar 

  9. Xu G, Yan Y, Liu Y (2014) The cardiovascular disease risks of nonthyroidal illness syndrome and inflammatory responses on patients with chronic kidney disease: from the association to clinical prognosis. Cardiovasc Ther 32(6):257–263

    Article  CAS  PubMed  Google Scholar 

  10. Afsar B, Yilmaz MI, Siriopol D et al (2016) Thyroid function and cardiovascular events in chronic kidney disease patients. J Nephrol. doi:10.1007/s40620-016-0300-y [Epub ahead of print]

    PubMed  Google Scholar 

  11. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461–470

    Article  CAS  PubMed  Google Scholar 

  12. Lechan RM, Fekete C (2004) Feedback regulation of thyrotropin-releasing hormone (TRH): mechanisms for the non-thyroidal illness syndrome. J Endocrinol Invest 27(6 Suppl):105–119

    CAS  PubMed  Google Scholar 

  13. Yu J, Koenig RJ (2000) Regulation of hepatocyte thyroxine 5′-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome. J Biol Chem 275(49):38296–38301

    Article  CAS  PubMed  Google Scholar 

  14. Menzies KJ, Robinson BH, Hood DA (2009) Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects. Am J Physiol Cell Physiol 296(2):C355–C362

    Article  CAS  PubMed  Google Scholar 

  15. Mohamedali M, ReddyMaddika S, Vyas A, Iyer V, Cheriyath P (2014) Thyroid disorders and chronic kidney disease. Int J Nephrol 2014:520281

    Article  PubMed  PubMed Central  Google Scholar 

  16. Basu G, Mohapatra A (2012) Interactions between thyroid disorders and kidney disease. Indian J Endocrinol Metab 16(2):204–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chandurkar V, Shik J, Randell E (2008) Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation. Endocr Pract 14(1):97–103

    Article  PubMed  Google Scholar 

  18. Xu G, Luo K, Liu H, Huang T, Fang X, Tu W (2015) The progress of inflammation and oxidative stress in patients with chronic kidney disease. Ren Fail 37(1):45–49

    Article  PubMed  Google Scholar 

  19. Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH (2007) Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab 92(2):491–496

    Article  CAS  PubMed  Google Scholar 

  20. Yilmaz MI, Sonmez A, Karaman M et al (2011) Low triiodothyronine alters flow-mediated vasodilatation in advanced nondiabetic kidney disease. Am J Nephrol 33(1):25–32

    Article  CAS  PubMed  Google Scholar 

  21. Asvold BO, Bjøro T, Vatten LJ (2011) Association of thyroid function with estimated glomerular filtration rate in a population-based study: the HUNT study. Eur J Endocrinol 164(1):101–105

    Article  PubMed  Google Scholar 

  22. Nakahama H, Sakaguchi K, Horita Y et al (2001) Treatment of severe hypothyroidism reduced serum creatinine levels in two chronic renal failure patients. Nephron 88(3):264–267

    Article  CAS  PubMed  Google Scholar 

  23. de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM (2009) Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 20(9):2075–2084

    Article  PubMed  PubMed Central  Google Scholar 

  24. Vidart J, Wajner SM, Leite RS et al (2014) N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial. J Clin Endocrinol Metab 99(12):4537–4545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wajner SM, Goemann IM, Bueno AL, Larsen PR, Maia AL (2011) IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. J Clin Invest 121(5):1834–1845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pappa TA, Vagenakis AG, Alevizaki M (2011) The nonthyroidal illness syndrome in the non-critically ill patient. Eur J Clin Invest 41(2):212–220

    Article  CAS  PubMed  Google Scholar 

  27. De Groot LJ (2006) Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin 22(1):57–86

    Article  PubMed  Google Scholar 

  28. Liu H, Yan W, Xu G (2014) Thyroid hormone replacement for nephrotic syndrome patients with euthyroid sick syndrome: a meta-analysis. Ren Fail 36(9):1360–1365

    Article  PubMed  Google Scholar 

  29. Pingitore A, Galli E, Barison A et al (2008) Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab 93(4):1351–1358

    Article  CAS  PubMed  Google Scholar 

  30. Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP (2000) A trial of thyroxine in acute renal failure. Kidney Int 57(1):293–298

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The research was supported by the National Natural Science Foundation of China (No. 81360122/H0518), and by the Natural Science Foundation of Jiangxi Province (No. 20143ACB21010).

Author information

Author notes

    Authors and Affiliations

    1. Department of Nephrology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China

      Wenjun Yan

    2. Medical Center of the Graduate School, Nanchang University, Nanchang, People’s Republic of China

      Lijuan Wang

    3. Department of Nephrology, The Second Affiliated Hospital of Nanchang University, 1, Minde Road, Nanchang, 330006, People’s Republic of China

      Tianlun Huang & Gaosi Xu

    Authors
    1. Wenjun Yan
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Lijuan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Tianlun Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Gaosi Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Gaosi Xu.

    Ethics declarations

    Conflict of interest

    All the authors declare that they have no potential conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    The study has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    W. Yan and L. Wang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Yan, W., Wang, L., Huang, T. et al. Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease: a single-blind controlled study. J Nephrol 30, 557–565 (2017). https://doi.org/10.1007/s40620-016-0341-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40620-016-0341-2

    Keywords

    Search

    Navigation