The Relation of Hepcidin to Iron Disorders, Inflammation and Hemoglobin in Chronic Kidney Disease

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 51 Cr-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 m 2 (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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Lucile Mercadel, Marie Metzger, Jean-Philippe Haymann, Eric Thervet, Jean-Jacques Boffa, et al.. The Relation of Hepcidin to Iron Disorders, Inflammation and Hemoglobin in Chronic Kidney Disease. PLoS ONE, Public Library of Science, 2014, 9 (6), pp.e99781. ⟨10.1371/journal.pone.0099781⟩. ⟨hal-01367481⟩

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