Human Iron Economy

Hepcidin is the master regulator of iron metabolism and plasma iron required to produce blood

• Plasma Iron is maintained normally at 10-30 µM
• Chronically >30 µM leads to iron deposition in tissues, injury, and organ damage
• Chronically <10 µM causes cellular dysfunction, and anemia
• Most iron is in the erythrocyte hemoglobin: 1 ml PRBC = 1mg fe

Hepcidin Potential Diagnostic Utility

• Hepcidin can diagnose iron deficiency in non-anemic patients
• Hepcidin can predict genetic disorders related to anemia (e.g. IRIDA)
• Hepcidin can predict non-responsiveness to oral iron
• Hepcidin can distinguish iron deficiency anemia (IDA) from anemia of chronic disease (ACD)
• Hepcidin measurement may improve the prediction of acute kidney injury (AKI) after heart surgery or in critical illness
• Hepcidin may predict mortality in critically ill patients with AKI
• Hepcidin may predict mortality in coronary artery disease
• Anemia defined by hepcidin is a risk factor for mortality post critical care discharge
• Hepcidin can predict iron deficiency in first-time blood donors

Adapted from A Pietrangelo. Hereditary <br>Hemochromatosis
A New Look at an Old Disease.<br>N Engl J Med 2004;
Adapted from A Pietrangelo. Hereditary
Hemochromatosis A New Look at an Old Disease.
N Engl J Med 2004; 350:2383-2397.

Serum hepcidin in various disease processes

DiseasePathophysiologyHepcidin Level
Iron deficiencyBlood loss, malnutritionLow/undetectable
Iron-refractory iron deficiency anemiaGenetic overproduction of hepcidinHigh normal to high
Anemia of hepatic adenomasAutonomous hepcidin production by tumorHigh? (only tumor mRNA measured)
Hereditary hemochromatosisGenetic hepcidin deficiency, varying severityUndetectable, low, or low for iron load
Secondary iron overloadTransfusions, iron therapyHigh
β-thalassemia intermedia (rare transfusions)Ineffective erythropoiesis, high erythropoietic driveLow
β-thalassemia major (regular transfusions)Ineffective erythropoiesis, moderated erythropoietic drive, secondary iron overloadLow or low for iron load
Hepatitis C, alcoholic liver diseaseSuppression of hepcidin by alcohol, virus or growth factorsLow
Infections, rheumatologic diseases, inflammatory bowel disease, cancerInflammationHigh
Chronic kidney diseasesDecreased clearance of hepcidin, variable inflammationHigh

Adapted from T Ganz and E Nemeth. Hepcidin and Disorders of Iron Metabolism. 2011. Ann Rev Med 62: 347-360.


Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors. Pasricha SR, McQuilten Z, Westerman M, Keller A, Nemeth E, Ganz T, Wood E. Haematologica 2011;96:1099-105.

Normalizing hepcidin predicts tmprss6 mutation status in patients with chronic iron deficiency. Heeney MM, Guo D, De Falco L, Campagna DR, Olbina G, Kao PP, et al. Blood 2018;132:448-52

Hepcidin levels predict non-responsiveness to oral iron therapy in patients with iron deficiency anemia. Bregman DB, Morris D, Koch TA, He A, Goodnough LT. American J Hematology 2012;88:97-101

Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia. Lasocki S, Baron G, Driss F, Westerman M, Puy H, Boutron I, et al. Intensive care medicine 2010;36:1044-8

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study. Albert C, Haase M, Albert A, Kropf S, Bellomo R, Westphal S, Westerman M, Braun-Dullaeus RC, Haase-Fielitz A. Ann Lab Med. 2020 Mar;40(2):131-141

Iron, Hepcidin, and Death in Human AKI. Leaf DE, Rajapurkar M, Lele SS, Mukhopadhyay B, Boerger EAS, Mc Causland FR, Eisenga MF, Singh K, Babitt JL, Kellum JA, Palevsky PM, Christov M, Waikar SS. J Am Soc Nephrol. 2019 Mar;30(3):493-504

Iron Metabolism, Hepcidin, and Mortality (the Ludwigshafen Risk and Cardiovascular Health Study). Grammer TB, Scharnagl H, Dressel A, Kleber ME, Silbernagel G, Pilz S, Tomaschitz A, Koenig W, Mueller-Myhsok B, März W, Strnad P. Clin Chem. 2019 Jul;65(7):849-861

Iron deficiency diagnosed using hepcidin on critical care discharge is an independent risk factor for death and poor quality of life at one year: An observational prospective study on 1161 patients. Lasocki S, Lefebvre T, Mayeur C, Puy H, Mebazaa A, Gayat E. Crit Care 2018;22:314

Clinical Immunoassay for Human Hepcidin Predicts Iron Deficiency in First-Time Blood Donors. Gutschow P, Han H, Olbina G, Westerman K, Nemeth E, Ganz T, Copeland K, Westerman M, Ostland V. JALM 2020: 943-953