Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia

Abstract

Levels of hepcidin, a major regulator of iron homeostasis, may identify patients with iron deficiency anemia (IDA) who will not respond to oral iron therapy. In this study, IDA patients underwent a 14-day trial (run-in) course of ferrous sulfate therapy. Nonresponders (Hgb increase <1 g/dL with 67% compliance rate) were randomized to IV ferric carboxymaltose (FCM; two injections of 750 mg) or further oral iron for 14 days. Screening hepcidin levels were 38.4 versus 11.3 ng/mL, P 5 0.0002 in nonresponders versus responders to a trial of oral iron. Hepcidin of > 20 ng/mL, showed sensitivity of 41.3%, specificity of 84.4%, and positive predictive value of 81.6% for predicting nonresponsiveness to oral iron. PPVs for ferritin> 30 ng/mL or transferrin saturation (TSAT)>15% were 59.2 and 55%, respectively. Negative predictive values for hepcidin, ferritin, and TSAT were 46.3, 22.7, and 19.7, respectively. FCM versus oral iron showed Hgb increases of 1 gm/ dL in 65.3% versus 20.8% (P < 0.0001) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL (P 5 0.0025), respectively. We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose. Nonresponse to oral iron therapy does not rule out IDA, since two-thirds of patients subsequently responded to intravenous iron. Am. J. Hematol. 88:97-101, 2013. V

Modern iron replacement therapy: clinical and pathophysiological insights

“…Thus, CHF represents a paradigmatic condition where recent pathophysiological insights on hepcidin appear to influence the choice on the most appropriate route of iron administration. The same concept was previously suggested by two retrospective studies in cancer patients [77], and in unselected IDA patients [78], where baseline hepcidin levels predicted subsequent responsiveness to oral iron. After initial technical difficulties, hepcidin assays are continuously improving, and a number of them showing good accuracy and reproducibility have been internationally validated [25].…”

Repletion of Iron Stores With the Use of Oral Iron Supplementation in Patients With Systolic Heart Failure

“…14,15 A recent study demonstrated that hepcidin levels predict nonresponsiveness to oral iron in non-HF patients with iron deficiencye anemia. 16 Unfortunately, circulating levels of hepcidin were not available in the present retrospective analysis. Gut edema is also suspected to play a role in impairing the absorption of oral iron that predisposes HF patients to iron deficiency.…”

Hepcidin in the diagnosis of iron disorders

“…Because hepcidin directly controls iron absorption, 4,5 serum hormone levels have the potential to predict poor responsiveness to oral iron, preventing possible detrimental effects of oral iron on the gut microbiome and metabolome 68 and eliminating delays before switching to IV iron. The usefulness of measuring basal hepcidin to personalize the optimal route of iron administration has been recently showed in patients with IDA, 62 chronic rheumatic anemia, 32 and chemotherapy-associated anemia. 63 However, large prospective trials are needed to confirm this attractive hypothesis.…”