No abstract

Plasma triiodothyronine (fT3) is a strong predictor of adverse clinical outcomes in various clinical conditions. Since fT3 in patients with end-stage renal diseases (ESRD) is frequently reduced and is associated with inflammation and cardiovascular damage, we prospectively tested the hypothesis that it predicts death in a cohort of 200 hemodialysis patients. Plasma fT3 was lower in ESRD patients (P<0.001) than in healthy subjects and in clinically euthyroid patients with normal renal function. During the follow-up 102 patients died. Patients who died had significantly lower plasma fT3 than those who survived (P<0.001) and in a Kaplan-Meyer analysis plasma fT3 was associated with death (P<0.001). On multivariate Cox's regression analyses, adjusting for a series of traditional and emerging risk factors including inflammation markers, patients with relatively higher plasma fT3 (hazard ratio (HR) (1 pg/ml increase in fT3)) had a 50% reduction in the risk of death (HR=0.50, 95% CI: 0.35-0.72) as compared to those having relatively lower fT3 levels. Of note, plasma fT3 captured most of the predictive power of interleukin-6 (IL-6) because this latter variable emerged as a significant predictor of death only in a model excluding fT3. Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population.

Because inflammation influences thyroid function, it was hypothesized that low plasma free triiodothyronine (fT3) in ESRD may be an unsuspected expression of the inflammatory state of these patients. This study investigated (1) the steady-state relationship between fT3 and inflammation markers (IL-6 and C-reactive protein) and markers of endothelial activation (intercellular adhesion molecule-1 [ICAM-1] and vascular cellular adhesion molecule-1 [VCAM-1]) in 200 hemodialysis (HD) patients and (2) the effect of intercurrent acute inflammatory/infectious processes on plasma fT3 in a group of 17 patients with chronic kidney disease (CKD). HD patients displayed lower (P < 0.001) plasma fT3 than healthy subjects (n = 31) and clinically euthyroid patients with chronic diseases and normal renal function (n = 262). When HD patients were subdivided into IL-6 tertiles, fT3 was progressively lower across tertile increments (P < 0.001). Accordingly, regression analysis showed strong and inverse associations (P < or = 0.002) between fT3 and IL-6, C-reactive protein, ICAM-1, and VCAM-1, and, with the exception of the ICAM-fT3 relationship, these associations remained highly significant (P < or = 0.004) in multiple regression analyses adjusting for demographic variables, risk factors, and other potential confounders. In patients who had CKD and were studied during intercurrent inflammatory/infectious processes, fT3 was significantly lower (P = 0.008) at the zenith of inflammation than after its resolution. Low circulating fT3 is frequently observed in inflammatory illnesses, and the same association exists in patients with CKD and in ESRD. This association may entail a causal link because fT3 is acutely and reversibly suppressed in patients with CKD during inflammatory processes triggered by intercurrent infections.

Abstract-Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (−75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the betweengroup difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitoltreated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment.