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. 2014 Jun 30;9(6):e99781.
doi: 10.1371/journal.pone.0099781. eCollection 2014.

The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease

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

The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease

Lucile Mercadal et al. PLoS One. .

Erratum in

Abstract

The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1-5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8-28.7] to 36.1 ng/mL [14.1-92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) <20% and ferritin <40 ng/mL) had the lowest hepcidin levels (5.0 ng/mL [0.7-11.7]), and those with a normal iron profile (TSAT ≥20% and ferritin ≥40), the highest (34.5 ng/mL [23.7-51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.

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Conflict of interest statement

Competing Interests: This study was partly funded by La Roche Ltd. M. Froissart has received consulting or lecture fees or research funds from Affymax, Genzyme, Hoffmann-La Roche, Novartis, Sandoz, Shire, Takeda, and Vifor International. M. Froissart 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. B.S. has received research funds from Amgen, Baxter, Genzyme (Sanofi), Fresenius, MSD, and GSK. Dr Barbara Sasu and Vimal Patel provided advised and performed hepcidin measurements at Amgen laboratories (Amgen Inc., Thousand Oaks, CA). In order to enable hepcidin measurements, this study was labelled as an Investigator Sponsored Study (BS) by Amgen. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Hepcidin concentration according to quintiles of ferritin (A), transferrin saturation (B) and total iron-binding capacity (C).
See this image and copyright information in PMC

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