Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

Abstract

Iron deficiency anemia (IDA) is a major problem in chronic kidney disease (CKD), causing increased mortality. Ferritin stores iron, representing iron status. Hepcidin binds to ferroportin, thereby inhibiting iron absorption/efflux. Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability. While intravenous iron therapy (IIT) is superior to oral iron therapy (OIT) in CKD patients with inflammation, OIT is as effective as IIT in those without. Inflammation reduces predictive values of ferritin and hepcidin for iron status and responsiveness to iron therapy. Upper limit of ferritin to predict iron overload is higher in CKD patients with inflammation than in those without. However, magnetic resonance imaging studies show lower cutoff levels of serum ferritin to predict iron overload in dialysis patients with apparent inflammation than upper limit of ferritin proposed by international guidelines. Compared to CKD patients with inflammation, optimal ferritin levels for IDA are lower in those without, requiring reduced iron dose and leading to decreased mortality. The management of IDA should differ between CKD patients with and without inflammation and include minimization of inflammation. Further studies are needed to determine the impact of inflammation on ferritin, hepcidin and therapeutic strategy for IDA in CKD.

Contemporary management of anaemia, erythropoietin resistance and cardiovascular risk in patients with advanced chronic kidney disease: a nationwide analysis

“…Inflammation is a key factor promoting ESA resistance, high ferritin levels and functional iron deficiency. However, several other factors interplay with hepcidin regulation and erythropoiesis in inflamed CKD patients [ 32 ], and measuring hepcidin levels has not been established as a reliable biomarker of functional iron deficiency in CKD [ 33 ].…”

The Influence of Inflammation on Anemia in CKD Patients

“…As it has been mentioned above, anemia of inflammation is characterized by increased ferritin levels, diminished iron and iron-binding capacity (transferrin) and the presence of iron in bone marrow macrophages, which indicate disturbed mobilization of iron from stores [57]. According to studies inflammation diminishes predictive values of ferritin and hepcidin for iron status and responsiveness to iron therapy [156]. Inflammation-mediated elevation in hepcidin concentration results in iron trapping within the macrophages and hepatocytes, resulting in functional iron deficiency (FID) and the requirement of a higher dose of IV iron to maintain Hb targets [157,158].…”

The prevalence of insomnia and restless legs syndrome among Japanese outpatients with rheumatic disease: A cross-sectional study

“…of ferritin [39,40], and clinicians should be aware that the administered iron may not be effective for erythropoiesis. The age of the present RLS group was significantly lower than that of the non-RLS group (p = 0.02).…”