Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance

Scientific Reports

Volumn 7, Issue 1, 2017, Pages

  Lee, Sung Woo ^a,b   Kim, Jeong Min ^c   Lim, Hye Jin ^d   Hwang, Young Hwan ^e   Kim, Soo Wan ^f   Chung, Wookyung ^g   Oh, Kook Hwan ^h   Ahn, Curie ^h   Lee, Kyu Beck ⁱ   Sung, Su Ah ^b  

^a Seoul National University   (South Korea)

^b Eulji University School of Medicine   (South Korea)

^c Lohas Geriatric Hospital   (South Korea)

^d Gimpo Woori Hospital   (South Korea)

^e Truewords Kidney Clinic and Institute   (South Korea)

^f Chonnam National University Medical School   (South Korea)

^g Gachon University   (South Korea)

^h Seoul National University Hospital   (South Korea)

ⁱ School of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIANEMIC AGENT; C REACTIVE PROTEIN; ERYTHROPOIETIN; HEPCIDIN;

ADULT; AGED; BLOOD; CHRONIC KIDNEY FAILURE; DRUG EFFECT; ERYTHROPOIESIS; FEMALE; GENETICS; GLOMERULUS FILTRATION RATE; HEMODIALYSIS; HUMAN; MALE; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY; SOUTH KOREA;

ADULT; AGED; C-REACTIVE PROTEIN; ERYTHROPOIESIS; ERYTHROPOIETIN; FEMALE; GLOMERULAR FILTRATION RATE; HEMATINICS; HEPCIDINS; HUMANS; MALE; MIDDLE AGED; RENAL DIALYSIS; RENAL INSUFFICIENCY, CHRONIC; REPUBLIC OF KOREA;

EID: 85021684224     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-04664-y     Document Type: Article

References (30)

1. Park, C. H., Valore, E. V., Waring, A. J., Ganz, T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276, 7806-7810, doi:10.1074/jbc.M008922200 (2001).
2. Ganz, T. Hepcidin and iron regulation, 10 years later. Blood 117, 4425-4433, doi:10.1182/blood-2011-01-258467 (2011).
3. Nemeth, E., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 2090-2093 (2004).
4. Ashby, D. R., et al. Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease. Kidney Int 75, 976-981, doi:10.1038/ki.2009.21 (2009).
5. Zaritsky, J., et al. Hepcidin-a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 4, 1051-1056, doi:10.2215/CJN.05931108 (2009).
6. Uehata, T., et al. Serum hepcidin-25 levels and anemia in non-dialysis chronic kidney disease patients: A cross-sectional study. Nephrol Dial Transplant 27, 1076-1083, doi:10.1093/ndt/gfr431 (2012).
7. Chand, S., et al. Serum hepcidin-25 and response to intravenous iron in patients with non-dialysis chronic kidney disease. J Nephrol 28, 81-88, doi:10.1007/s40620-014-0083-y (2015).
8. Peters, H. P., Laarakkers, C. M., Swinkels, D. W., Wetzels, J. F. Serum hepcidin-25 levels in patients with chronic kidney disease are independent of glomerular filtration rate. Nephrol Dial Transplant 25, 848-853, doi:10.1093/ndt/gfp546 (2010).
9. Gaillard, C. A., et al. Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FINDCKD Trial. PloS one 11, e0157063, doi:10.1371/journal.pone.0157063 (2016).
10. Mercadal, L., et al. The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease. PloS one 9, e99781, doi:10.1371/journal.pone.0099781 (2014).
11. 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 27, 504-510, doi:10.1002/jcla.21634 (2013).
12. Yang, L. N., Zhang, P., Tang, F., Wang, G., Li, F. E. Correlation between hepcidin level and renal anemia. Genet Mol Res 13, 7407-7410, doi:10.4238/2014.September.12.6 (2014).
13. Lukaszyk, E., et al. Iron Status and Inflammation in Early Stages of Chronic Kidney Disease. Kidney Blood Press Res 40, 366-373, doi:10.1159/000368512 (2015).
14. Drakou, A., et al. Assessment of serum bioactive hepcidin-25, soluble transferrin receptor and their ratio in predialysis patients: Correlation with the response to intravenous ferric carboxymaltose. Blood Cells Mol Dis 59, 100-105, doi:10.1016/j. bcmd.2016.05.006 (2016).
15. Vanholder, R., et al. Review on uremic toxins: Classification, concentration, interindividual variability. Kidney Int 63, 1934-1943, doi:10.1046/j.1523-1755.2003.00924.x (2003).
16. Kemna, E. H., Tjalsma, H., Willems, H. L., Swinkels, D. W. Hepcidin: From discovery to differential diagnosis. Haematologica 93, 90-97 (2008).
17. Ganz, T., Olbina, G., Girelli, D., Nemeth, E., Westerman, M. Immunoassay for human serum hepcidin. Blood 112, 4292-4297, doi:10.1182/blood-2008-02-139915 (2008).
18. Dahlfors, G., et al. Validation of a competitive ELISA assay for the quantification of human serum hepcidin. Scand J Clin Lab Invest 75, 652-658 (2015).
19. Kroot, J. J., et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders. Clin Chem 56, 1570-1579, doi:10.1373/clinchem.2010.149187 (2010).
20. Laarakkers, C. M., et al. Improved mass spectrometry assay for plasma hepcidin: Detection and characterization of a novel hepcidin isoform. PloS one 8, e75518, doi:10.1371/journal.pone.0075518 (2013).
21. van der Putten, K., et al. Hepcidin-25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease/chronic heart failure patients. Eur J Heart Fail 12, 943-950, doi:10.1093/eurjhf/hfq099 (2010).
22. Brigandi, R. A., et al. A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. Am J Kidney Dis 67, 861-871, doi:10.1053/j.ajkd.2015.11.021 (2016).
23. Nemeth, E., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113, 1271-1276 (2004).
24. Campostrini, N., et al. Serum levels of the hepcidin-20 isoform in a large general population: The Val Borbera study. J Proteomics 76 Spec No., 28-35, doi:10.1016/j.jprot.2012.08.006 (2012).
25. Oh, K. H., et al. KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): Design and methods. BMC Nephrol 15, 1471-2369 (2014).
26. Levey, A. S., et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145, 247-254 (2006).
27. Stevens, P. E., Levin, A., Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group, M. Evaluation and management of chronic kidney disease: Synopsis of the kidney disease: Improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158, 825-830, doi:10.7326/0003-4819-158-11-201306040-00007 (2013).
28. KDIGO kidney group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl 2, 279-335 (2012).
29. Koulouridis, I., Alfayez, M., Trikalinos, T. A., Balk, E. M., Jaber, B. L. Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: A metaregression analysis. Am J Kidney Dis 61, 44-56, doi:10.1053/j.ajkd.2012.07.014 (2013).
30. Vega, A., et al. Dose equivalence between continuous erythropoietin receptor activator (CERA), Darbepoetin and Epoetin in patients with advanced chronic kidney disease. Hippokratia 18, 315-318 (2014).