Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb 19;9(2):e84144.
doi: 10.1371/journal.pone.0084144. eCollection 2014.

A 3-marker index improves the identification of iron disorders in CKD anaemia

Lucile Mercadal  1 , Marie Metzger  2 , Jean Philippe Haymann  3 , Eric Thervet  4 , Jean-Jacques Boffa  5 , Martin Flamant  6 , François Vrtovsnik  7 , Cédric Gauci  8 , Marc Froissart  9 , Bénédicte Stengel  2 ; NephroTest Study Group
Collaborators, Affiliations

A 3-marker index improves the identification of iron disorders in CKD anaemia

Lucile Mercadal et al. PLoS One. .

Erratum in

  • PLoS One. 2014;9(6):e100606

Abstract

Background: Iron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia.

Methods: We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total iron binding capacity (TIBC<50 µmol/L) in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR) by (51)Cr-EDTA renal clearance; 199 also had hepcidin measures.

Results: The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID) to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m(2) (interaction p<0.0001). In patients with mGFR<30 mL/min/1.73 m(2), the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia.

Conclusions: The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m(2). Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: LM has received consulting or lecture fees research funds from Hospal, Gambro, Hoffmann-La Roche, and Vifor; MF from Affymax, Genzyme, Hoffmann-La Roche, Novartis, Sandoz, Shire, Takeda, and Vifor International; BS from Amgen, Baxter, Genzyme (Sanofi), Fresenius, MSD, and GSK. MF has been employed by Amgen since January 1, 2011, but was a full-time academic associate professor during the time of study conception and data collection. The competing interest does not alter the authors' adherence to the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Hemoglobin, transferrin saturation (TSAT), ferritin and transferrin iron binding capacity (TIBC) according to mGFR level, by gender.
Men are in solid line and women in dotted line.
Figure 2
Figure 2. Iron profiles distribution according to gender (2a) and mGFR (2b).
See this image and copyright information in PMC

References

    1. Moranne O, Froissart M, Rossert J, Gauci C, Boffa JJ, et al. (2009) Timing of onset of CKD related metabolic complications. J Am Soc Nephrol 20 (1) 164–71. - PMC - PubMed
    1. Herzog CA, Muster HA, Li S, Collins MSA (2004) Impact of congestive heart failure, chronic kidney disease, and anemia on survival in the Medicare population. Journal of Cardiac Failure 10 (6) 467–472. - PubMed
    1. Mercadal L, Metzger M, Casadevall N, Haymann JP, Karras A, et al. (2012) and NephroTest Study Group (2012) Timing and determinants of erythropoietin deficiency in chronic kidney disease. Clin J Am Soc Nephrol 7 (1) 35–42. - PMC - PubMed
    1. Stancu S, Stanciu A, Zugravu A, Bârsan L, Dumitru D, et al. (2010) Bone marrow iron, iron indices and the response to intravenous iron in patients with non-dialysis-dependent CKD. Am J Kidney Dis 55: 639–647. - PubMed
    1. Fishbane S, Pollack S, Feldman HI, Joffe MM (2009) Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988–2004. Clin J Am Soc Nephrol 4 (1) 57–61. - PMC - PubMed

Publication types