Background: Transferrin saturation (TSAT) is an index that represents the iron-binding capacity of transferrin, which is the main transport protein for iron, and is widely used to evaluate iron status. Objective: To evaluate the prognostic importance of TSAT in Japanese patients on maintenance hemodialysis (MHD). Methods: A total of 398 patients on MHD were recruited and divided into 3 groups on the basis of their baseline TSAT levels (<20, 20–40, and >40%). Results: There was no difference in the proportion of patients on erythropoiesis-stimulating agents or iron supplements between the 3 groups. During a mean follow-up period of 52.2 ± 1 6.3 months, 130 patients died of cardiovascular causes (n = 63, 15.8%) or infection (n = 47, 11.8%). Compared with the reference group (TSAT 20–40%), patients with a TSAT <20% had a significantly higher all-cause mortality rate (6.44 vs. 9.55 events per 100 patient-years, p = 0.0452). Kaplan-Meier analysis showed that all-cause mortality rate was significantly higher in patients with TSAT <20% than in the other 2 groups (p = 0.0353). Conclusions: Low TSAT was a significant independent risk factor for all-cause mortality in a cohort of Japanese patients on MHD. The findings of this study suggest that the adverse clinical outcomes in patients with low TSAT can be partly attributed to infection-related iron deficiency.

1.
Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018.
Am J Kidney Dis
. 2018 Mar;71(3):423–35.
2.
Hayashi T, Joki N, Tanaka Y, Hase H. Anaemia and early phase cardiovascular events on haemodialysis.
Nephrology (Carlton)
. 2015 Dec;20 Suppl 4:1–6.
3.
Yamamoto T, Miyazaki M, Nakayama M, Yamada G, Matsushima M, Sato M, et al. Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study.
Clin Exp Nephrol
. 2016 Aug;20(4):595–602.
4.
Tanaka K, Watanabe T, Takeuchi A, Ohashi Y, Nitta K, Akizawa T, et al.; CKD-JAC Investigators. Cardiovascular events and death in Japanese patients with chronic kidney disease.
Kidney Int
. 2017 Jan;91(1):227–34.
5.
Hörl WH. Anaemia management and mortality risk in chronic kidney disease.
Nat Rev Nephrol
. 2013 May;9(5):291–301.
6.
Babitt JL, Lin HY. Mechanisms of anemia in CKD.
J Am Soc Nephrol
. 2012 Oct;23(10):1631–4.
7.
KDOQI; National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis. 2006 May;47(5 Suppl 3):S11–45.
8.
KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012 Aug;2(4):282–335.
9.
Yamamoto H, Nishi S, Tomo T, Masakane I, Saito K, Nangaku M, et al. 2015 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease.
Ren Replace Ther.
2017;3(1):36.
10.
Ellervik C, Andersen HU, Tybjærg-Hansen A, Frandsen M, Birgens H, Nordestgaard BG, et al. Total mortality by elevated transferrin saturation in patients with diabetes.
Diabetes Care
. 2013 Sep;36(9):2646–54.
11.
Stack AG, Mutwali AI, Nguyen HT, Cronin CJ, Casserly LF, Ferguson J. Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.
QJM
. 2014 Aug;107(8):623–33.
12.
Koo HM, Kim CH, Doh FM, Lee MJ, Kim EJ, Han JH, et al. The relationship of initial transferrin saturation to cardiovascular parameters and outcomes in patients initiating dialysis.
PLoS One
. 2014 Feb;9(2):e87231.
13.
Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error.
J Am Soc Nephrol
. 1993 Nov;4(5):1205–13.
14.
Shinzato T, Nakai S, Fujita Y, Takai I, Morita H, Nakane K, et al. Determination of Kt/V and protein catabolic rate using pre- and postdialysis blood urea nitrogen concentrations.
Nephron
. 1994;67(3):280–90.
15.
Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation.
Clin J Am Soc Nephrol
. 2006 Sep;1 Suppl 1:S4–8.
16.
Vlagopoulos PT, Tighiouart H, Weiner DE, Griffith J, Pettitt D, Salem DN, et al. Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.
J Am Soc Nephrol
. 2005 Nov;16(11):3403–10.
17.
Portolés J, López-Gómez JM, Aljama P. A prospective multicentre study of the role of anaemia as a risk factor in haemodialysis patients: the MAR Study.
Nephrol Dial Transplant
. 2007 Feb;22(2):500–7.
18.
Weiss G, Goodnough LT. Anemia of chronic disease.
N Engl J Med
. 2005 Mar;352(10):1011–23.
19.
Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al.; CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease.
N Engl J Med
. 2006 Nov;355(20):2085–98.
20.
Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al.; CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia.
N Engl J Med
. 2006 Nov;355(20):2071–84.
21.
Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, et al.; TREAT Investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.
N Engl J Med
. 2009 Nov;361(21):2019–32.
22.
Camaschella C. Iron-deficiency anemia.
N Engl J Med
. 2015 May;372(19):1832–43.
23.
Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells.
Metallomics
. 2014 Apr;6(4):748–73.
24.
Kalantar-Zadeh K, Lee GH, Miller JE, Streja E, Jing J, Robertson JA, et al. Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients.
Am J Kidney Dis
. 2009 May;53(5):823–34.
25.
Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients.
J Am Soc Nephrol
. 2005 Oct;16(10):3070–80.
26.
Pollak VE, Lorch JA, Shukla R, Satwah S. The importance of iron in long-term survival of maintenance hemodialysis patients treated with epoetin-alfa and intravenous iron: analysis of 9.5 years of prospectively collected data.
BMC Nephrol
. 2009 Feb;10(1):6.
27.
Gaweda AE, Bhat P, Maglinte GA, Chang CL, Hill J, Park GS, et al. TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients.
Hemodial Int
. 2014 Jan;18(1):38–46.
28.
Bross R, Zitterkoph J, Pithia J, Benner D, Rambod M, Kovesdy CP, et al. Association of serum total iron-binding capacity and its changes over time with nutritional and clinical outcomes in hemodialysis patients.
Am J Nephrol
. 2009;29(6):571–81.
29.
Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure.
Eur Heart J
. 2010 Aug;31(15):1872–80.
30.
Sempos CT, Looker AC, Gillum RF, Makuc DM. Body iron stores and the risk of coronary heart disease.
N Engl J Med
. 1994 Apr;330(16):1119–24.
31.
Kim KS, Son HG, Hong NS, Lee DH. Associations of serum ferritin and transferrin % saturation with all-cause, cancer, and cardiovascular disease mortality: Third National Health and Nutrition Examination Survey follow-up study.
J Prev Med Public Health
. 2012 May;45(3):196–203.
32.
Wells BJ, Mainous AG 3rd, King DE, Gill JM, Carek PJ, Geesey ME. The combined effect of transferrin saturation and low density lipoprotein on mortality.
Fam Med
. 2004 May;36(5):324–9.
33.
Reunanen A, Takkunen H, Knekt P, Seppänen R, Aromaa A. Body iron stores, dietary iron intake and coronary heart disease mortality.
J Intern Med
. 1995 Sep;238(3):223–30.
34.
Robinson BM, Port FK. International hemodialysis patient outcomes comparisons revisited: the role of practice patterns and other factors.
Clin J Am Soc Nephrol
. 2009 Dec;4 Suppl 1:S12–7.
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.