| Institution: | 1. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA;2. 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;6. Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA;g. Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN;h. Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN |
| Abstract: | ObjectiveGiven 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 MethodsAmong 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.ResultsIn 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.ConclusionAmong 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. |
