title: Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.
abstract: BACKGROUND
  Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.
  
  
  METHODS
  249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003-2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.
  
  
  RESULTS
  Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).
  
  
  CONCLUSIONS
  We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define "high risk" populations in CKD.
authors.affiliation: Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Kidney and Transplant Institute, Imperial College, London, United Kingdom.
authors.forename: Damien R
authors.initials: DR
authors.lastname: Ashby
authors.affiliation: Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kurtz
authors.affiliation: Division of Nephrology, McGill University, Montreal, Canada.
authors.forename: Ahsan
authors.initials: A
authors.lastname: Alam
authors.affiliation: Department of Clinical Chemistry, Imperial College, London, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Busbridge
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine 4, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raff
authors.affiliation: Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Clinical Trial Unit, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Peter U
authors.initials: PU
authors.lastname: Heuschmann
authors.affiliation: Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schramm
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003928:Diabetic Nephropathies / Q000150:complications* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D064451:Hepcidins / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000401:mortality*; D016014:Linear Models; D008297:Male; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D064451:Hepcidins; C545475:hepcidin 25, human