Data from: Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease

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.