Serum hepcidin-25 levels in patients with chronic kidney disease are independent of glomerular filtration rate.
BACKGROUND
Hepcidin is a key regulator of iron homeostasis and levels are elevated in patients with chronic kidney disease (CKD). Hepcidin may explain the often observed imbalance in iron metabolism in patients with CKD. We evaluated the influence of estimated glomerular filtration rate (eGFR) on serum levels of hepcidin-25 and its isoforms in patients with renal dysfunction.


METHODS
Serum levels of the biologically active hepcidin-25 and its isoforms were determined in CKD and dialysis patients by a mass spectrometry-based assay.


RESULTS
In 83 patients with CKD not requiring dialysis, serum hepcidin-25 levels were not significantly increased (5.1 nM versus 4.2 nM, P = 0.30) and positively correlated with ferritin (r = 0.74, P < 0.01). Multiple regression analysis showed ferritin to be the only significant predictor of hepcidin-25 levels. Serum hepcidin-25 levels were not dependent on eGFR. In contrast, hepcidin-20 and total hepcidin levels showed an independent significant inverse correlation with eGFR. In 48 haemodialysis patients, median hepcidin-25 levels were significantly higher than in CKD patients (9.4 nM versus 5.1 nM, P < 0.001) and again strongly correlated with ferritin (r = 0.79, P < 0.001).


CONCLUSIONS
eGFR is not a major determinant of serum hepcidin-25 levels. In contrast, the hepcidin isoforms hepcidin-20 and hepcidin-22 accumulate in patients with renal impairment.
Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. h.peters@aig.umcn.nl
Hilde P E
HP
Peters
Coby M M
CM
Laarakkers
Dorine W
DW
Swinkels
Jack F M
JF
Wetzels
D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005293:Ferritins / Q000097:blood; D005919:Glomerular Filtration Rate / Q000502:physiology*; D064451:Hepcidins; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D020033:Protein Isoforms / Q000097:blood; D006435:Renal Dialysis
D023181:Antimicrobial Cationic Peptides; D064451:Hepcidins; D010446:Peptide Fragments; D020033:Protein Isoforms; C542573:hepcidin (6-25), human; C545475:hepcidin 25, human; D005293:Ferritins