Hepcidin--a potential novel biomarker for iron status in chronic kidney disease.
OBJECTIVE
Hepcidin is a key regulator of iron homeostasis, but its study in the setting of chronic kidney disease (CKD) has been hampered by the lack of validated serum assays.


METHODS
This study reports the first measurements of bioactive serum hepcidin using a novel competitive ELISA in 48 pediatric (PCKD2-4) and 32 adult (ACKD2-4) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD (PCKD5D) on peritoneal dialysis.


RESULTS
When compared with their respective controls (pediatric median = 25.3 ng/ml, adult = 72.9 ng/ml), hepcidin was significantly increased in PCKD2-4 (127.3 ng/ml), ACKD2-4 (269.9 ng/ml), and PCKD5D (652.4 ng/ml). Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia, iron status, inflammation, and renal function. In PCKD2-4 (R(2) = 0.57), only ferritin correlated with hepcidin. In ACKD2-4 (R(2) = 0.78), ferritin and soluble transferrin receptor were associated with hepcidin, whereas GFR was inversely correlated. In PCKD5D (R(2) = 0.52), percent iron saturation and ferritin were predictors of hepcidin. In a multivariate analysis that incorporated all three groups (R(2) = 0.6), hepcidin was predicted by ferritin, C-reactive protein, and whether the patient had stage 5D versus stages 2 to 4 CKD.


CONCLUSIONS
These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance.
Zaritsky
Joshua
J
Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. jzaritsky@mednet.ucla.edu
Young
Brian
B
Wang
He-Jing
HJ
Westerman
Mark
M
Olbina
Gordana
G
Nemeth
Elizabeta
E
Ganz
Tomas
T
Rivera
Seth
S
Nissenson
Allen R
AR
Salusky
Isidro B
IB
D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards; D004920:Erythropoiesis; D005260:Female; D005293:Ferritins / Q000097:blood; D005919:Glomerular Filtration Rate; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D010530:Peritoneal Dialysis; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000628:therapy; D015203:Reproducibility of Results; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins; D033862:Iron-Binding Proteins; D011956:Receptors, Cell Surface; C027293:ferritin receptor; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron