title: Association of hepcidin-25 with survival after kidney transplantation.
abstract: BACKGROUND
  Hepcidin is considered the master regulator of iron homoeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron-restricted anaemia. Meanwhile, serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR), which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore, prospectively determined the association of serum hepcidin with risk of graft failure, cardiovascular mortality and all-cause mortality in RTR.
  
  
  METHODS
  Serum hepcidin was assessed in an extensively phenotyped RTR cohort by dual-monoclonal sandwich ELISA specific immunoassay. Statistical analyses were performed using univariate linear regression followed by stepwise backward linear regression. Cox proportional hazard regression models were performed to determine prospective associations.
  
  
  RESULTS
  We included 561 RTR (age 51 ± 12 years). Mean haemoglobin (Hb) was 8·6 ± 1·0 mM. Median [IQR] serum hepcidin was 7·2 [3·2-13·4] ng/mL. Mean estimated glomerular filtration rate was 47 ± 16 mL/min/1·73 m2. In univariate Cox regression analyses, serum hepcidin was not associated with risk of graft failure, cardiovascular mortality or all-cause mortality. Notably, after adjustment for high sensitivity C-reactive protein and ferritin, serum hepcidin became negatively associated with all-cause mortality (hazard ratio 0·89; 95% confidence interval 0·80-0·99, P = 0·03).
  
  
  CONCLUSIONS
  In this study, we did not find an association between serum hepcidin and outcomes, that is graft failure, cardiovascular mortality or all-cause mortality. Based on our results, it is questionable whether serum hepcidin may be used to predict a beneficial effect of hepcidin antagonists.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Michele F
authors.identifier: http://orcid.org/0000-0002-2484-6233
authors.initials: MF
authors.lastname: Eisenga
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Berger
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sloan
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood*; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D002423:Cause of Death; D004797:Enzyme-Linked Immunosorbent Assay; D005293:Ferritins / Q000097:blood; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000601:surgery*; D016030:Kidney Transplantation; D016014:Linear Models; D008875:Middle Aged; D009026:Mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D064451:Hepcidins; C545475:hepcidin 25, human; D002097:C-Reactive Protein; D005293:Ferritins
keywords: Determinants; graft failure; hepcidin; mortality; renal transplantation