Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jul 6, 2015; 4(3): 415-422
Published online Jul 6, 2015. doi: 10.5527/wjn.v4.i3.415
Low T3 syndrome and long-term mortality in chronic hemodialysis patients
Stylianos Fragidis, Konstantinos Sombolos, Elias Thodis, Stylianos Panagoutsos, Euthymia Mourvati, Maria Pikilidou, Aikaterini Papagianni, Ploumis Pasadakis, Vasilios Vargemezis
Stylianos Fragidis, Elias Thodis, Stylianos Panagoutsos, Euthymia Mourvati, Ploumis Pasadakis, Vasilios Vargemezis, Department of Nephrology, Medical School, Democritus University of Thrace, 68100 Alexadroupolis, Greece
Stylianos Fragidis, Konstantinos Sombolos, Maria Pikilidou, Renal Unit, “George Papanikolaou” General Hospital, 57010 Thessaloniki, Greece
Aikaterini Papagianni, Department of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece
Author contributions: All authors contributed to this manuscript.
Ethics approval statement: The study was reviewed and approved by the Institutional Review Board of both the Dimocritus University Hospital in Alexandroupoli and the “George Papanikolaou” General Hospital in Thessaloniki, as part of my PhD thesis (Registration No: 1221/12-12-2006).
Clinical trial registration: The study was not interventional, randomized or controlled. All patients during the study were receiving routine examination and laboratory evaluation and were followed-up for mortality as part of their routine care. Thus a registration identification number of the study was not necessary.
Informed consent statement: All involved patients gave a verbal informed consent for the legal use of their blood samples and handling of their personal data before their enrollment.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: There are no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Stylianos Fragidis, MD, Department of Nephrology, Medical School, Democritus University of Thrace, University Campus, 68100 Alexadroupolis, Greece. sfragidis@yahoo.com
Telephone: +30-69-77659570 Fax: +30-23-10273703
Received: December 22, 2014
Peer-review started: December 23, 2014
First decision: January 8, 2015
Revised: March 9, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: July 6, 2015
Processing time: 196 Days and 17.2 Hours
Abstract

AIM: To investigate the predictive value of low freeT3 for long-term mortality in chronic hemodialysis (HD) patients and explore a possible causative role of chronic inflammation.

METHODS: One hundred fourteen HD patients (84 males) consecutively entered the study and were assessed for thyroid function and two established markers of inflammation, high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Monthly blood samples were obtained from all patients for three consecutive months during the observation period for evaluation of thyroid function and measurement of inflammatory markers. The patients were then divided in two groups based on the cut-off value of 1.8 pg/mL for mean plasma freeT3, and were prospectively studied for a mean of 50.3 ± 30.8 mo regarding cumulative survival. The prognostic power of low serum fT3 levels for mortality was assessed using the Kaplan-Meier method and univariate and multivariate regression analysis.

RESULTS: Kaplan-Meier survival curve showed a negative predictive power for low freeT3. In Cox regression analysis low freeT3 remained a significant predictor of mortality after adjustment for age, diabetes mellitus, hypertension, hsCRP, serum creatinine and albumin. Regarding the possible association with inflammation, freeT3 was correlated with hsCRP, but not IL-6, and only at the first month of the study.

CONCLUSION: In chronic hemodialysis patients, low plasma freeT3 is a significant predictor of all-cause mortality. Further studies are required to identify the underlying mechanisms of this association.

Keywords: C-reactive protein; Hemodialysis; Inflammation; Interleukin-6; Low T3 syndrome; Mortality

Core tip: Monthly blood samples were obtained from 114 patients for three consecutive months during the observation period for evaluation of thyroid function and measurement of inflammatory markers high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Patients were then followed-up for 7-years. Low mean freeT3 (< 1.8 pg/mL) emerged as a significant predictor of all-cause mortality after adjustment for age, diabetes mellitus, hypertension, hsCRP, serum creatinine and albumin. However, freeT3 was correlated with hsCRP, but not IL-6, and only at the first month suggesting that further studies are required to identify the underlying pathogenetic mechanisms of the association between thyroid function and survival.