Bone marrow iron distribution, hepcidin, and ferroportin expression in renal anemia

Abstract

Objectives: The hepcidin-ferroportin system is involved in both conditions associated with iron-restricted erythropoiesis in renal anemia: iron deficiency and anemia of chronic disorders. As serum hepcidin could aid diagnosis, we investigated its relationships with bone marrow iron distribution, hepcidin-ferroportin expression in bone marrow cells, and peripheral iron indices in non-dialysis chronic kidney disease (CKD) patients.

Methods: Fifty-four epoetin and iron naive CKD patients entered this prospective, observational study. According to bone marrow iron distribution (iliac crest biopsy, Perls' stain), 26 had iron deficiency anemia, 21 anemia of chronic disorders and 7 had normal iron stores. Medullar hepcidin and ferroportin expression (immunofluorescence (IF), semiquantitative scales) and serum hepcidin (Hep25 - ELISA) were the main studied parameters.

Results: Low hepcidin and high ferroportin expression by erythroblast and macrophage were seen in iron deficiency anemia, while the opposites were true in anemia of chronic disorders. In regression analysis, higher Hep25 and ferritin predicted hepcidin expression (R(2)=0.48; P < 0.0001), while lower ferritin and Hep25 - predicted ferroportin expression (R(2) = 0.29; P = 0.003) by erythroblast; inflammation had no contribution. In ROC analysis, serum hepcidin and ferritin had similar moderate utility in differentiating iron deficiency anemia from anemia of chronic disorders (AUC 0.63 95% CI 0.47-0.79 and 0.76 95% CI 0.61-0.90, respectively).

Conclusions: Thus, in anemic epoetin naive non-dialysis CKD patients, hepcidin and ferroportin expression by erythroblast and macrophage are closely related to bone marrow iron distribution. Although the hepcidin-ferroportin system seems regulated by ferritin-driven Hep25, serum hepcidin and peripheral iron indices are of little help in describing bone marrow iron status.

Keywords: Bone marrow; Chronic kidney disease; Hepcidin–ferroportin system; Iron distribution; Renal anemia.