Connie M Rhee1, Kamyar Kalantar-Zadeh2, Vanessa Ravel1, Elani Streja2, Amy S You1, Steven M Brunelli3, Danh V Nguyen4, Gregory A Brent5, Csaba P Kovesdy6. 1. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA. 2. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA; Tibor Rubin Veterans Affairs Medical Center, Long Beach, CA. 3. DaVita Clinical Research, Minneapolis, MN. 4. Division of General Internal Medicine, University of California Irvine School of Medicine, Orange, CA. 5. Division of Endocrinology, Diabetes and Metabolism, David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA. 6. Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN; Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN. Electronic address: ckovesdy@uthsc.edu.
Abstract
OBJECTIVE: Given that patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) have a disproportionately higher prevalence of hypothyroidism compared with their non-CKD counterparts, we sought to determine the association between thyroid status, defined by serum thyrotropin (TSH) levels, and mortality among a national cohort of patients with NDD-CKD. PATIENTS AND METHODS: Among 227,422 US veterans with stage 3 NDD-CKD with 1 or more TSH measurements during the period October 1, 2004, to September 30, 2012, we first examined the association of thyroid status, defined by TSH categories of less than 0.5, 0.5 to 5.0 (euthyroidism), and more than 5.0 mIU/L, with all-cause mortality. We then evaluated 6 granular TSH categories: less than 0.1, 0.1 to less than 0.5, 0.5 to less than 3.0, 3.0 to 5.0, more than 5.0 to 10.0, and more than 10.0 mIU/L. We concurrently examined thyroid status, thyroid-modulating therapy, and mortality in sensitivity analyses. RESULTS: In expanded case-mix adjusted Cox analyses, compared with euthyroidism, baseline and time-dependent TSH levels of more than 5.0 mIU/L were associated with higher mortality (adjusted hazard ratios [aHRs] [95% CI], 1.19 [1.15-1.24] and 1.23 [1.19-1.28], respectively), as were baseline and time-dependent TSH levels of less than 0.5 mIU/L (aHRs [95% CI], 1.18 [1.15-1.22] and 1.41 [1.37-1.45], respectively). Granular examination of thyroid status showed that incrementally higher TSH levels of 3.0 mIU/L or more were associated with increasingly higher mortality in baseline and time-dependent analyses, and TSH categories of less than 0.5 mIU/L were associated with higher mortality (reference, 0.5-<3.0 mIU/L) in baseline analyses. In time-dependent analyses, untreated and undertreated hypothyroidism and untreated hyperthyroidism were associated with higher mortality (reference, spontaneous euthyroidism), whereas hypothyroidism treated-to-target showed lower mortality. CONCLUSION: Among US veterans with NDD-CKD, high-normal TSH (≥3.0 mIU/L) and lower TSH (<0.5 mIU/L) levels were associated with higher death risk. Interventional studies identifying the target TSH range associated with the greatest survival in patients with NDD-CKD are warranted.
OBJECTIVE: Given that patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) have a disproportionately higher prevalence of hypothyroidism compared with their non-CKD counterparts, we sought to determine the association between thyroid status, defined by serum thyrotropin (TSH) levels, and mortality among a national cohort of patients with NDD-CKD. PATIENTS AND METHODS: Among 227,422 US veterans with stage 3 NDD-CKD with 1 or more TSH measurements during the period October 1, 2004, to September 30, 2012, we first examined the association of thyroid status, defined by TSH categories of less than 0.5, 0.5 to 5.0 (euthyroidism), and more than 5.0 mIU/L, with all-cause mortality. We then evaluated 6 granular TSH categories: less than 0.1, 0.1 to less than 0.5, 0.5 to less than 3.0, 3.0 to 5.0, more than 5.0 to 10.0, and more than 10.0 mIU/L. We concurrently examined thyroid status, thyroid-modulating therapy, and mortality in sensitivity analyses. RESULTS: In expanded case-mix adjusted Cox analyses, compared with euthyroidism, baseline and time-dependent TSH levels of more than 5.0 mIU/L were associated with higher mortality (adjusted hazard ratios [aHRs] [95% CI], 1.19 [1.15-1.24] and 1.23 [1.19-1.28], respectively), as were baseline and time-dependent TSH levels of less than 0.5 mIU/L (aHRs [95% CI], 1.18 [1.15-1.22] and 1.41 [1.37-1.45], respectively). Granular examination of thyroid status showed that incrementally higher TSH levels of 3.0 mIU/L or more were associated with increasingly higher mortality in baseline and time-dependent analyses, and TSH categories of less than 0.5 mIU/L were associated with higher mortality (reference, 0.5-<3.0 mIU/L) in baseline analyses. In time-dependent analyses, untreated and undertreated hypothyroidism and untreated hyperthyroidism were associated with higher mortality (reference, spontaneous euthyroidism), whereas hypothyroidism treated-to-target showed lower mortality. CONCLUSION: Among US veterans with NDD-CKD, high-normal TSH (≥3.0 mIU/L) and lower TSH (<0.5 mIU/L) levels were associated with higher death risk. Interventional studies identifying the target TSH range associated with the greatest survival in patients with NDD-CKD are warranted.
Authors: Connie M Rhee; Steven Kim; Daniel L Gillen; Tolga Oztan; Jiaxi Wang; Rajnish Mehrotra; Sooraj Kuttykrishnan; Danh V Nguyen; Steven M Brunelli; Csaba P Kovesdy; Gregory A Brent; Kamyar Kalantar-Zadeh Journal: J Clin Endocrinol Metab Date: 2015-01-29 Impact factor: 5.958
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Authors: Miklos Z Molnar; Kamyar Kalantar-Zadeh; Evan H Lott; Jun Ling Lu; Sandra M Malakauskas; Jennie Z Ma; Darryl L Quarles; Csaba P Kovesdy Journal: J Am Coll Cardiol Date: 2013-11-21 Impact factor: 24.094
Authors: Connie M Rhee; Matthew Budoff; Gregory Brent; Amy S You; Peter Stenvinkel; Alejandra Novoa; Ferdinand Flores; Sajad Hamal; Christopher Dailing; April Kinninger; Tracy Nakata; Csaba P Kovesdy; Danh V Nguyen; Kamyar Kalantar-Zadeh Journal: Cardiorenal Med Date: 2022-05-12 Impact factor: 4.360
Authors: Guillermo Navarro Blackaller; Jonathan S Chávez-Iñiguez; Elsa Edith Carreón-Bautista; Francisco Javier González-Torres; Miroslava Villareal-Contreras; José Roberto Barrientos Avalos; Pablo Maggiani Aguilera; Francisco Romo Rosales; Torres Mayorga José Antonio; Juan Alberto Gómez Fregoso; Jorge Isaac Michel Gonzalez; Guillermo García-García Journal: Kidney Int Rep Date: 2020-12-03