Low Triiodothyronine Alters Flow-Mediated Vasodilatation in Advanced Nondiabetic Kidney Disease

Abstract

Background/Aims: Subclinical or frank hypothyroidism is causally implicated in endothelial dysfunction. Since the plasma concentration of the active form of thyroid hormone, triiodothyronine (T₃), is reduced in chronic kidney disease (CKD), where endothelial function is frequently altered, low T₃ may be a factor implicated in this disturbance in CKD patients. Methods: We investigated the relationship between flow-mediated vasodilatation (FMD) and thyroid hormones in a series of 217 nondiabetic patients with stage 3–4 CKD. Results: The plasma concentration of free T₃ (fT₃) was closely associated with FMD (r = 0.38; p < 0.001). fT₃ was also inversely associated with hemoglobin (r = –0.41; p < 0.001), systolic pressure (r = –0.28; p < 0.001) and the plasma concentration of the endogenous inhibitor of NO synthase, asymmetric dimethylarginine (ADMA; r = –0.18; p = 0.007). However, adjustment for ADMA markedly attenuated the fT₃-FMD link, a phenomenon suggesting that raised plasma ADMA, possibly driven by low fT₃, at least in part mediates the adverse effects of low T₃ on endothelial function in CKD. Conclusions: Low T₃ in patients with moderate-to-severe CKD is a marker of endothelial dysfunction. This study sets a solid rationale for designing specific intervention studies aimed at clarifying the nature (causal or not causal) of the endothelial function-T₃ link in CKD.

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

“…In support of the association between T3 and cardiovascular death in our study, a previous report (11) in patients with moderate to severe kidney disease reported that T3 levels inversely associated with flow-mediated vasodilation and that this observation was dependent on multivariate adjustment for asymmetric dimethylarginine levels. At a cardiac level, low T3 levels in CKD patients are associated with reduced left ventricular function, increased left ventricular mass (13), and elevated intimamedia thickness (12).…”

“…However, growing evidence suggests participation of T3 in the pathophysiology of endothelial dysfunction (11), atherosclerosis (12), and cardiac abnormalities (13) of CKD patients. Some studies, with somewhat conflicting results, have also implicated thyroid alterations in the mortality risk of CKD patients (14)(15)(16).…”

Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

“…Moreover, it has been shown that serum free-T3 (fT3) level associated with impaired endothelial function as assessed by flowmediated dilation in nondiabetic nondialyzed patients with chronic kidney disease (CKD) (17). It is presently unknown whether atherosclerotic features commonly found in dialysis stages are associated with low T3 levels.…”

A Low Serum Free Triiodothyronine Level is Associated with Epicardial Adipose Tissue in Peritoneal Dialysis Patients

“…T3 is a potent stimulus for NO-dependent vasodilatation in the forearm in healthy subjects. It has also been shown that there is an association between low fT3 levels and endothelial dysfunction in stage 3-4 chronic kidney disease patients 13) . We also observed a significant relationship between the fT3 levels and FMD in our study; which supports that fT3 affects the endothelial function.…”

“…On the other hand, Tatar et al recently demonstrated that low fT3 levels are associated with carotid atherosclerosis in HD patients 11,12) . Yilmaz et al demonstrated a relationship between low fT3 levels and endothelial dysfunction in patients suffering from renal failure 13) . Moreover, there is a well-accepted association between low fT3 levels and mortality in patients suffering from renal failure 14) .…”