Hepcidin-25 in chronic hemodialysis patients is related to residual kidney function and not to treatment with erythropoiesis stimulating agents.
Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 ± 13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance.
Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands. n.c.vanderweerd@amc.uva.nl
Neelke C
NC
van der Weerd
Muriel P C
MP
Grooteman
Michiel L
ML
Bots
Marinus A
MA
van den Dorpel
Claire H
CH
den Hoedt
Albert H A
AH
Mazairac
Menso J
MJ
Nubé
E Lars
EL
Penne
Carlo A
CA
Gaillard
Jack F M
JF
Wetzels
Erwin T
ET
Wiegerinck
Dorine W
DW
Swinkels
Peter J
PJ
Blankestijn
Piet M
PM
Ter Wee
D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006397:Hematinics / Q000627:therapeutic use; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D006435:Renal Dialysis
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D006397:Hematinics; D064451:Hepcidins; D010446:Peptide Fragments; C542573:hepcidin (6-25), human; C545475:hepcidin 25, human; D004921:Erythropoietin; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron