Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease

• Published in: Kidney international Vol. 75; no. 9; pp. 976 - 981
• Main Authors: Ashby, Damien R., Gale, Daniel P., Busbridge, Mark, Murphy, Kevin G., Duncan, Neill D., Cairns, Tom D., Taube, David H., Bloom, Stephen R., Tam, Frederick W.K., Chapman, Richard S., Maxwell, Patrick H., Choi, Peter
• Format: Journal Article
• Language: English
• Published: Basingstoke Elsevier Inc 01.05.2009; Nature Publishing Group; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Anemia - metabolism; Antimicrobial Cationic Peptides - blood; Antimicrobial Cationic Peptides - drug effects; Biological and medical sciences; Case-Control Studies; Circadian Rhythm; dialysis; erythropoietin; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Female; ferritin; Ferritins - blood; Glomerular Filtration Rate; hepcidin; Hepcidins; Humans; iron; kidney disease; Kidney Diseases - blood; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Radioimmunoassay; Recombinant Proteins; Renal failure; Young Adult; dialysis; iron; kidney disease; ferritin; hepcidin; erythropoietin; Kidney disease; Nephrology; Urinary system disease; Erythropoietin; Ferritin; Iron; Urology; Blood plasma; Nephropathy; Treatment; Polypeptide; Renal failure; Dialysis; Hepcidin
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2009.21

Hepcidin is a critical inhibitor of iron export from macrophages, enterocytes, and hepatocytes. Given that it is filtered and degraded by the kidney, its elevated levels in renal failure have been suggested to play a role in the disordered iron metabolism of uremia, including erythropoietin resistance. Here, we used a novel radioimmunoassay for hepcidin-25, the active form of the hormone, to measure its levels in renal disease. There was a significant diurnal variation of hepcidin and a strong correlation to ferritin levels in normal volunteers. In 44 patients with mild to moderate kidney disease, hepcidin levels were significantly elevated, positively correlated with ferritin but inversely correlated with the estimated glomerular filtration rate. In 94 stable hemodialysis patients, hepcidin levels were also significantly elevated, but this did not correlate with interleukin-6 levels, suggesting that increased hepcidin was not due to a general inflammatory state. Elevated hepcidin was associated with anemia, but, intriguingly, the erythropoietin dose was negatively correlated with hepcidin, suggesting that erythropoietin suppresses hepcidin levels. This was confirmed in 7 patients when hepcidin levels significantly decreased after initiation of erythropoietin treatment. Our results show that hepcidin is elevated in renal disease and suggest that higher hepcidin levels do not predict increased erythropoietin requirements.