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

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          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.

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          Thyroid dysfunction and kidney disease.

          J Díez, P. Iglesias-Bonilla (2009)
          Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T(3), can be considered as a marker for survival in patients with kidney disease.
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            Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease.

            Fang-Chi Hsu, Glenn Chertow, Winston Go … (2005)
            Previous studies have suggested a higher prevalence of thyroid abnormalities in persons with end-stage renal disease. However, little is known regarding the epidemiology of thyroid disorders in persons with less severe kidney dysfunction. We used data from the Third National Health and Nutrition Examination Survey to examine the prevalence of hypothyroidism (clinical and subclinical) at different levels of estimated glomerular filtration rate (GFR). We used multivariable logistic regression to evaluate the association between GFR and prevalent hypothyroidism. Among 14,623 adult participants with serum creatinine and thyroid function test results, the mean age was 48.7 years, and 52.6% were women. The prevalence of hypothyroidism increased with lower levels of GFR (in units of mL/min/1.73 m(2)), occurring in 5.4% of subjects with GFR >/=90, 10.9% with GFR 60-89, 20.4% with GFR 45-59, 23.0% with GFR 30-44, and 23.1% with GFR /=90 mL/min/1.73 m(2), reduced GFR was associated with an increased risk of hypothyroidism, after adjusting for age, gender, and race/ethnicity: adjusted odds ratio 1.07 (95% confidence interval: 0.86-1.32) for GFR 60-89, 1.57 (1.11-2.22) for GFR 45-59, 1.81 (1.04-3.16) for GFR 30-44, and 1.97 (0.69-5.61) for GFR <30 mL/min/1.73 m(2) (P= 0.008 for trend). Among a nationally representative sample of adults, reduced glomerular filtration rate was associated with a higher prevalence of hypothyroidism, with many subclinical cases. Future studies are needed to determine the potential adverse effects of subclinical and clinical hypothyroidism in persons with chronic kidney disease.
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              Prevalence of subclinical hypothyroidism in patients with chronic kidney disease.

              Michel Chonchol, G Salvagno, Giovanni Targher … (2008)
              Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined. Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR. Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR or=90 ml/min per 1.73 m(2) to 17.9% at an estimated GFR or=60 ml/min per 1.73 m(2), those with estimated GFR <60 ml/min per 1.73 m(2) had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations. These findings suggest that subclinical primary hypothyroidism is a relatively common condition ( approximately 18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.
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                Author and article information

                Journal
                Journal ID (publisher-id): AJN
                Journal ID (nlm-ta): Am J Nephrol
                Journal ID (doi): 10.1159/issn.0250-8095
                Title: American Journal of Nephrology
                Publisher: S. Karger AG
                ISSN (Print): 0250-8095
                ISSN (Electronic): 1421-9670
                Publication date Subscription-year: 2011
                Publication date (Print): April 2011
                Publication date (Electronic): 08 March 2011
                Volume: 33
                Issue: 4
                Pages: 305-312
                Affiliations
                aDivision of Nephrology, Ataturk Training and Research Hospital, and bDivision of Nephrology, Ege University School of Medicine, Izmir, Turkey; cDivision of Renal Medicine, Centre for Gender Medicine and Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
                Author notes
                *Ozkan Gungor, Division of Nephrology, Ege University School of Medicine, TR–35100 Bornova, Izmir (Turkey), Tel. +90 232 390 4254, E-Mail ozkangungor@yahoo.com.tr
                Article
                Publisher ID: 324883 Other ID: Am J Nephrol 2011;33:305–312
                DOI: 10.1159/000324883
                PubMed ID: 21389695
                SO-VID: 62d2057a-2281-4c7e-9f10-86bcfcb884f5
                Copyright © © 2011 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 10 January 2011
                Date accepted : 04 February 2011
                Page count
                Figures: 1, Tables: 4, Pages: 8
                Categories
                Subject: Original Report: Patient-Oriented, Translational Research

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Low-T3 syndrome,Survival,Free triiodothyronine,Hemodialysis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Low-T3 syndrome, Survival, Free triiodothyronine, Hemodialysis

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