Nutritional State Alters the Association between Free Triiodothyronine Levels and Mortality in Hemodialysis Patients

Abstract

Background: Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. Methods: A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. Results: Baseline fT3 was 1.47 ± 0.43 (0.01–2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. Conclusions: Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.

Baseline Levels and Trimestral Variation of Triiodothyronine and Thyroxine and Their Association with Mortality in Maintenance Hemodialysis Patients

“…Furthermore, Zoccali et al (14) reported that as adjustment for fT3 abrogated the association between inflammation and patient outcome, fT3 may be an intermediate pathologic indicator of systemic inflammation. In our data, as well as in Ozen et al (5), adjustment for inflammation did not affect the link between T3 and mortality. Also, associations between trimestral thyroid hormone changes and variation of inflammatory markers were somewhat weak and inconsistent in our study.…”

“…Whereas earlier studies (5,14,17) only studied the association between T3 and fT3 and all-cause mortality, our study adds that this mortality prediction is mainly attributable to CV causes. The lack of mortality prediction observed by Fernández-Reyes et al (15) could relate to the selection of patients having survived at least 12 months, the low number of events encountered, and the strict inclusion criteria that excluded, among others, patients with abnormal fT3 and free T4 (fT4) levels.…”

“…In this sense, our analysis shows that patients with both baseline and longitudinal low T3 levels have a relatively shorter time to death, possibly suggesting a stronger impact of thyroid hormones on short-term outcome. The study from Ozen et al (5) showed that adjustment for CRP and s-albumin abrogated the association between fT3 and all-cause mortality, and the authors concluded that poor nutritional status confounded this association. The acute-phase reactant nature of s-albumin makes these results difficult to contextualize (24,25), and in our study, adjustment for inflammation (IL-6) and malnutrition did not affect this association.…”

“…We could further confirm and expand these observations in a cohort of euthyroid incident HD patients, in which the variance of all-cause and cardiovascular (CV) mortality was better explained by T3 than by fT3 levels (16). In contrast, a study in 87 HD patients could not confirm these findings (15), and a retrospective report found that the association between fT3 and mortality was confounded by the nutritional status of the patients (5). Whereas existing evidence on the association between thyroid hormones and mortality is limited to studies considering single measurements of hormone levels, it is currently unknown whether thyroid hormone fluctuation over time affects mortality hazards.…”

“…Recent reports suggest that as many as 70% of patients with ESRD present with low T3 levels (2)(3)(4)(5) and as many as 20%-25% have subclinical hypothyroidism (6,7). The underlying pathophysiology of these derangements is likely multifactorial, involving iodine retention, altered serum protein binding capacity, systemic inflammation, and peripheral deiodinase activity (8,9).…”