Effects of additional iron doses on hepcidin-25 level in hemodialysis patients without evident iron deficiency.

BACKGROUND: Serum hepcidin-25 is not only a marker of iron stores, but also an acute phase reactant, and it could fluctuate in response to erythropoietic activity.

STUDY DESIGN: Prospective interventional, 3-months duration, investigating the influence of additional intravenous (IV) iron on hepcidin-25 in hemodialysis (HD) patients without obvious iron deficiency (ID).

SETTINGS AND PARTICIPANTS: Single HD unit, 41 patients.

MEASUREMENTS: Hepcidin-25 (ELISA method), ferritin, transferrin, transferrin saturation (TSAT), C-reactive protein and serum albumin--at baseline and assessment; hemoglobin, iron and darbepoetin doses--monthly.

INTERVENTION: Additional IV iron doses were administered, driven by hemoglobin trend: iron dose increased by 25 % for each 0.5 g/dL hemoglobin drop for baseline ferritin of 200-800 ng/mL. Iron was discontinued for stable hemoglobin or >13 g/dL. Darbepoetin doses were adjusted for 11 g/dL target hemoglobin.

RESULTS: At baseline, 21 % of patients had "optimal" iron status; none had "absolute" or "functional" ID, while 15 % had iron "overload." Hepcidin levels were 112.8 (95 % CI 105.3-121.8) ng/mL. Hemoglobin was within the target range. After 75 % augmentation in iron doses, hepcidin-25 decreased by 70 %. Transferrin increased, and TSAT and ferritin decreased. Prevalence of "functional" ID rose to 24 % and of iron "overload" declined to 0 %. Reversal of iron-restricted erythropoiesis was further sustained by unchanging hemoglobin and decrease in darbepoetin doses and darbepoetin resistance index. Reasonable associations between assessment versus baseline ratios for hepcidin-25 and transferrin (inverse), TSAT and ferritin (direct) were found. Despite the increased inflammation, decrease in transferrin and increase in ferritin ratios were independent predictors of hepcidin variability (model of logistic regression r (2) 0.34; p < 0.0001).

LIMITATIONS: Low number of participants, less diabetic nephropathy/vascular diseases than general dialyzed population, uncontrolled design, use of hepcidin-25 ELISA assay.

CONCLUSIONS: Activation of erythropoiesis by additional IV iron administration overcomes moderate inflammation in suppressing hepcidin-25. Thus, hepcidin-25 could be clinically useful to evaluate iron status in patients with renal anemia.