Thyroid Status and Mortality in a Prospective Hemodialysis Cohort

Connie M Rhee, Amy S You, Danh V Nguyen, Steven M Brunelli, Matthew J Budoff, Elani Streja, Tracy Nakata, Csaba P Kovesdy, Gregory A Brent, Kamyar Kalantar-Zadeh, Connie M Rhee, Amy S You, Danh V Nguyen, Steven M Brunelli, Matthew J Budoff, Elani Streja, Tracy Nakata, Csaba P Kovesdy, Gregory A Brent, Kamyar Kalantar-Zadeh

Abstract

Context and objective: Compared with the general population, hemodialysis patients have a substantially higher risk of hypothyroidism, as defined by an elevated serum thyrotropin (TSH) level, and cardiovascular mortality. Whereas an elevated TSH is associated with cardiovascular disease and death in the general population, associations among dialysis patients have been inconsistent.

Design, setting, participants, and main outcome: We examined 541 hemodialysis patients from 17 southern California dialysis centers in the prospective Hypothyroidism, Cardiovascular Health, and Survival study who underwent protocolized measurement of repeated serum TSH levels every 6 months from 2013 to 2015. Associations between TSH tertiles (<1.28, 1.28 to <2.14, and 2.14 to 86.7 mIU/L) and mortality were estimated using time-dependent Cox models with four adjustment levels. In sensitivity analyses, we excluded patients receiving thyroid hormone supplementation.

Results: Compared with the lowest TSH tertile, the highest TSH tertile was associated with a 2.2- to 2.5-fold higher mortality risk in unadjusted, case-mix, expanded case-mix+laboratory, and expanded case-mix+laboratory+medication models [hazard ratios (95% confidence interval), 2.54 (1.32 to 4.89), 2.53 (1.30 to 4.93), 2.19 (1.11 to 4.32), and 2.28 (1.45 to 3.58), respectively]. We observed a consistent trend between higher TSH tertiles and numerically higher mortality risk across all models. Similar findings were observed in analyses excluding patients receiving thyroid hormone supplementation.

Conclusion: In time-dependent analyses, TSH levels in the high-normal to high range were independently associated with higher death risk in hemodialysis patients. Further studies are indicated to determine whether normalization of TSH levels with thyroid hormone supplementation improves survival in this population.

Trial registration: ClinicalTrials.gov NCT01415570.

Copyright © 2017 by the Endocrine Society

Figures

Figure 1.
Figure 1.
Association of time-dependent TSH tertiles with all-cause mortality. Case-mix analyses adjusted for age, sex, race, ethnicity, and diabetes. Expanded case-mix+laboratory analyses adjusted for covariates in the case-mix model, plus dialysis vintage, vascular access, body mass index, and serum albumin level. Expanded case-mix+laboratory+medication analyses adjusted for covariates in the expanded case-mix+laboratory model, plus thyroid hormone supplementation use. TSH tertiles 1, 2, and 3 correspond to TSH levels of

Figure 2.

Sensitivity analyses of the association…

Figure 2.

Sensitivity analyses of the association between time-dependent TSH tertiles and (a) all-cause mortality…

Figure 2.
Sensitivity analyses of the association between time-dependent TSH tertiles and (a) all-cause mortality with medication exclusion (n = 504) and (b) with removal of TSH outliers [defined as TSH values greater than the ~99.5th percentile of observed values (TSH level >16.0 mIU/L; n = 538)]. Case-mix analyses adjusted for age, sex, race, ethnicity, and diabetes. Expanded case-mix+laboratory analyses adjusted for covariates in case-mix model, plus dialysis vintage, vascular access, body mass index, and serum albumin level. (b) Expanded case-mix+laboratory+medication analyses adjusted for covariates in the expanded case-mix+laboratory model, plus thyroid hormone supplementation use. (a) TSH tertiles 1, 2, and 3 correspond to TSH levels of

Figure 3.

Subgroup analyses of the association…

Figure 3.

Subgroup analyses of the association between time-dependent TSH tertiles with all-cause mortality adjusted…

Figure 3.
Subgroup analyses of the association between time-dependent TSH tertiles with all-cause mortality adjusted for expanded case-mix+laboratory covariates. Expanded case-mix+laboratory analyses adjusted for age, sex, race, ethnicity, diabetes, dialysis vintage, vascular access, body mass index, and serum albumin level. TSH tertiles 1, 2, and 3 correspond to TSH levels of
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References
    1. Chonchol M, Lippi G, Salvagno G, Zoppini G, Muggeo M, Targher G. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3(5):1296–1300. - PMC - PubMed
    1. Lo JC, Chertow GM, Go AS, Hsu CY. Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int. 2005;67(3):1047–1052. - PubMed
    1. Rhee CM, Alexander EK, Bhan I, Brunelli SM. Hypothyroidism and mortality among dialysis patients. Clin J Am Soc Nephrol. 2013;8(4):593–601. - PMC - PubMed
    1. Rhee CM, Kalantar-Zadeh K, Streja E, Carrero JJ, Ma JZ, Lu JL, Kovesdy CP. The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease. Nephrol Dial Transplant. 2015;30(2):282–287. - PMC - PubMed
    1. Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, Kuttykrishnan S, Nguyen DV, Brunelli SM, Kovesdy CP, Brent GA, Kalantar-Zadeh K. Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab. 2015;100(4):1386–1395. - PMC - PubMed
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Figure 2.
Figure 2.
Sensitivity analyses of the association between time-dependent TSH tertiles and (a) all-cause mortality with medication exclusion (n = 504) and (b) with removal of TSH outliers [defined as TSH values greater than the ~99.5th percentile of observed values (TSH level >16.0 mIU/L; n = 538)]. Case-mix analyses adjusted for age, sex, race, ethnicity, and diabetes. Expanded case-mix+laboratory analyses adjusted for covariates in case-mix model, plus dialysis vintage, vascular access, body mass index, and serum albumin level. (b) Expanded case-mix+laboratory+medication analyses adjusted for covariates in the expanded case-mix+laboratory model, plus thyroid hormone supplementation use. (a) TSH tertiles 1, 2, and 3 correspond to TSH levels of

Figure 3.

Subgroup analyses of the association…

Figure 3.

Subgroup analyses of the association between time-dependent TSH tertiles with all-cause mortality adjusted…

Figure 3.
Subgroup analyses of the association between time-dependent TSH tertiles with all-cause mortality adjusted for expanded case-mix+laboratory covariates. Expanded case-mix+laboratory analyses adjusted for age, sex, race, ethnicity, diabetes, dialysis vintage, vascular access, body mass index, and serum albumin level. TSH tertiles 1, 2, and 3 correspond to TSH levels of
Similar articles
Cited by
References
    1. Chonchol M, Lippi G, Salvagno G, Zoppini G, Muggeo M, Targher G. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008;3(5):1296–1300. - PMC - PubMed
    1. Lo JC, Chertow GM, Go AS, Hsu CY. Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int. 2005;67(3):1047–1052. - PubMed
    1. Rhee CM, Alexander EK, Bhan I, Brunelli SM. Hypothyroidism and mortality among dialysis patients. Clin J Am Soc Nephrol. 2013;8(4):593–601. - PMC - PubMed
    1. Rhee CM, Kalantar-Zadeh K, Streja E, Carrero JJ, Ma JZ, Lu JL, Kovesdy CP. The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease. Nephrol Dial Transplant. 2015;30(2):282–287. - PMC - PubMed
    1. Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, Kuttykrishnan S, Nguyen DV, Brunelli SM, Kovesdy CP, Brent GA, Kalantar-Zadeh K. Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab. 2015;100(4):1386–1395. - PMC - PubMed
Show all 38 references
Publication types
MeSH terms
Associated data
[x]
Cite
Copy Download .nbib .nbib
Format: AMA APA MLA NLM
Figure 3.
Figure 3.
Subgroup analyses of the association between time-dependent TSH tertiles with all-cause mortality adjusted for expanded case-mix+laboratory covariates. Expanded case-mix+laboratory analyses adjusted for age, sex, race, ethnicity, diabetes, dialysis vintage, vascular access, body mass index, and serum albumin level. TSH tertiles 1, 2, and 3 correspond to TSH levels of

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