Iron Balance and the Role of Hepcidin in Chronic Kidney Disease

Seminars in Nephrology

Volumn 36, Issue 2, 2016, Pages 87-93

  Ganz, Tomas ^a   Nemeth, Elizabeta ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Anemia; Inflammation; Iron deficiency; Renal failure

Indexed keywords

2 OXOGLUTARIC ACID; BONE MORPHOGENETIC PROTEIN; C REACTIVE PROTEIN; FERRITIN; FERROCHELATASE; FERROPORTIN; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; PROTOPORPHYRIN ZINC; TRANSFERRIN RECEPTOR; CATION TRANSPORT PROTEIN; IRON; METAL TRANSPORTING PROTEIN 1; TRANSFERRIN;

BINDING AFFINITY; CELL FUNCTION; CHRONIC KIDNEY DISEASE; CONCENTRATION (PARAMETERS); ERYTHROID CELL; HOMEOSTASIS; HORMONAL REGULATION; HORMONE ACTION; HORMONE BLOOD LEVEL; HORMONE METABOLISM; HORMONE RELEASE; HUMAN; IRON ABSORPTION; IRON BALANCE; IRON DEFICIENCY; IRON KINETICS; IRON METABOLISM; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; REVIEW; SIGNAL TRANSDUCTION; CHRONIC KIDNEY FAILURE; COMPLICATION; DEFICIENCY; ERYTHROPOIESIS; INTESTINE ABSORPTION; IRON DEFICIENCY ANEMIA; MACROPHAGE; METABOLISM;

ANEMIA, IRON-DEFICIENCY; CATION TRANSPORT PROTEINS; ERYTHROPOIESIS; HEPCIDINS; HOMEOSTASIS; HUMANS; INTESTINAL ABSORPTION; IRON; MACROPHAGES; RENAL INSUFFICIENCY, CHRONIC; TRANSFERRIN;

EID: 84962658729     PISSN: 02709295     EISSN: 15584488     Source Type: Journal    
DOI: 10.1016/j.semnephrol.2016.02.001     Document Type: Review

References (53)

1. Andrews N.C. Forging a field: the golden age of iron biology. Blood 2008, 112:219-230.
2. Hentze M.W., Muckenthaler M.U., Galy B., et al. Two to tango: regulation of Mammalian iron metabolism. Cell 2010, 142:24-38.
3. Ganz T. Systemic iron homeostasis. Physiol Rev 2013, 93:1721-1741.
4. Cook J.D. Diagnosis and management of iron-deficiency anaemia. Best Pract Res Clin Haematol 2005, 18:319-332.
5. Cogswell M.E., Looker A.C., Pfeiffer C.M., et al. Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003-2006. Am J Clin Nutr 2009, 89:1334-1342.
6. Chen J.J. Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: relevance to anemias. Blood 2007, 109:2693-2699.
7. Breuer W., Ronson A., Slotki I.N., et al. The assessment of serum nontransferrin-bound iron in chelation therapy and iron supplementation. Blood 2000, 95:2975-2982.
8. Jenkitkasemwong S., Wang C.Y., Coffey R., et al. SLC39A14 is required for the development of hepatocellular iron overload in murine models of hereditary hemochromatosis. Cell Metab 2015, 22:138-150.
9. Nemeth E., Tuttle M.S., Powelson J., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004, 306:2090-2093.
10. Core A.B., Canali S., Babitt J.L. Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis. Front Pharmacol 2014, 5:104.
11. Silvestri L., Pagani A., Nai A., et al. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab 2008, 8:502-511.
12. Zhang A.S., Anderson S.A., Wang J., et al. Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. Blood 2011, 117:1687-1699.
13. Arezes J., Jung G., Gabayan V., et al. Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus. Cell Host Microbe 2015, 17:47-57.
14. Nemeth E., Rivera S., Gabayan V., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004, 113:1271-1276.
15. Besson-Fournier C., Latour C., Kautz L., et al. Induction of activin B by inflammatory stimuli upregulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling. Blood 2012, 120:431-439.
16. Kautz L., Jung G., Valore E.V., et al. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014, 46:678-684.
17. Ashby D.R., Gale D.P., Busbridge M., et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 2010, 95:505-508.
18. Salahudeen A.A., Bruick R.K. Maintaining mammalian iron and oxygen homeostasis: sensors, regulation, and cross-talk. Ann N Y Acad Sci 2009, 1177:30-38.
19. Schofield C.J., Ratcliffe P.J. Signalling hypoxia by HIF hydroxylases. Biochem Biophys Res Commun 2005, 338:617-626.
20. Shah Y.M., Xie L. Hypoxia-inducible factors link iron homeostasis and erythropoiesis. Gastroenterology 2014, 146:630-642.
21. Liu Q., Davidoff O., Niss K., et al. Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. J Clin Invest 2012, 122:4635-4644.
22. Park C.H., Valore E.V., Waring A.J., et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001, 276:7806-7810.
23. Ganz T., Olbina G., Girelli D., et al. Immunoassay for human serum hepcidin. Blood 2008, 112:4292-4297.
24. Preza G.C., Pinon R., Ganz T., et al. Cellular catabolism of the iron-regulatory peptide hormone hepcidin. PLoS One 2013, 8:e58934.
25. Rivera S., Nemeth E., Gabayan V., et al. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005, 106:2196-2199.
26. Nemeth E., Preza G.C., Jung C.L., et al. The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006, 107:328-333.
27. Kroot J.J., Laarakkers C.M., Geurts-Moespot A.J., et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders. Clin Chem 2010, 56:1570-1579.
28. Addo L., Ikuta K., Tanaka H., et al. The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS). Int J Hematol 2015, Epub ahead of print.
29. Babitt J.L., Lin H.Y. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012, 23:1631-1634.
30. Minutolo R., Locatelli F., Gallieni M., et al. Anaemia management in non-dialysis chronic kidney disease (CKD) patients: a multicentre prospective study in renal clinics. Nephrol Dial Transplant 2013, 28:3035-3045.
31. Goch J., Birgegard G., Danielson B.G., et al. Iron absorption in patients with chronic uremia on maintenance hemodialysis and in healthy volunteers measured with a simple oral iron load test. Nephron 1996, 73:403-406.
32. Zaritsky J., Young B., Wang H.J., et al. Hepcidin-a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 2009, 4:1051-1056.
33. Sohal A.S., Gangji A.S., Crowther M.A., et al. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006, 118:417-422.
34. Atkinson M., Kim J., Roy C., et al. Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol 2015, 30:635-643.
35. Mercadel L., Metzger M., Haymann J.P., et al. The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease. PLoS One 2014, 9:e99781.
36. Troutt J.S., Butterfield A.M., Konrad R.J. Hepcidin-25 concentrations are markedly increased in patients with chronic kidney disease and are inversely correlated with estimated glomerular filtration rates. J Clin Lab Anal 2013, 27:504-510.
37. Zaritsky J., Young B., Gales B., et al. Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. Clin J Am Soc Nephrol 2010, 5:1010-1014.
38. Kuragano T., Shimonaka Y., Kida A., et al. Determinants of hepcidin in patients on maintenance hemodialysis: role of inflammation. Am J Nephrol 2010, 31:534-540.
39. Cavill I., Macdougall I.C. Functional iron deficiency. Blood 1993, 82:1377.
40. Johnson D.W., Pollock C.A., Macdougall I.C. Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology (Carlton) 2007, 12:321-330.
41. Fishbane S., Besarab A. Mechanism of increased mortality risk with erythropoietin treatment to higher hemoglobin targets. Clin J Am Soc Nephrol 2007, 2:1274-1282.
42. Fishbane S., Frei G.L., Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis 1995, 26:41-46.
43. Bullock G.C., Delehanty L.L., Talbot A.L., et al. Iron control of erythroid development by a novel aconitase-associated regulatory pathway. Blood 2010, 116:97-108.
44. Han A.P., Yu C., Lu L., et al. Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. EMBO J 2001, 20:6909-6918.
45. Skikne B.S. Serum transferrin receptor. Am J Hematol 2008, 83:872-875.
46. Cohen L.A., Gutierrez L., Weiss A., et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010, 116:1574-1584.
47. Moore C., Ormseth M., Fuchs H. Causes and significance of markedly elevated serum ferritin levels in an academic medical center. J Clin Rheumatol 2013, 19:324-328.
48. Pietrangelo A. The ferroportin disease. Blood. Cell Mol Dis 2004, 32:131-138.
49. Brugnara C., Mohandas N. Red cell indices in classification and treatment of anemias: from M.M. Wintrobes's original 1934 classification to the third millennium. Curr Opin Hematol 2013, 20:222-230.
50. Braun J. Erythrocyte zinc protoporphyrin. Kidney Int Suppl 1999, 69:S57-S60.
51. Nemeth E. Anti-hepcidin therapy for iron-restricted anemias. Blood 2013, 122:2929-2931.
52. Bonomini M., Del Vecchio L., Sirolli V., et al. New treatment approaches for the anemia of CKD. Am J Kidney Dis 2016, 67:133-142.
53. Besarab A., Chernyavskaya E., Motylev I., et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients. J Am Soc Nephrol 2015, Epub ahead of print.