Hepcidin‐25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease/chronic heart failure patients†

Abstract

AimsErythropoietin (EPO) resistance, an important cause of anaemia in patients with heart and renal failure, is associated with increased mortality. The hypothesis of the present study was that exogenous EPO decreases hepcidin levels and that the decrease in hepcidin levels upon EPO treatment is related to the bone marrow response. Methods and resultsIn the EPOCARES trial, patients with renal failure (glomerular filtration rate 20-70 mL/min), heart failure, and anaemia were randomized to receive 50 IU/kg/week EPO (n ¼ 20) or not (n ¼ 13). Haemoglobin (Hb), hepcidin-25, ferritin, reticulocytes, serum transferrin receptor (sTfR), IL-6, and high-sensitivity C-reactive protein were measured at baseline and during treatment. Hepcidin-25 was measured by weak cation exchange chromatography/ matrix assisted laser desorption ionization time-of-flight mass spectrometry. Baseline hepcidin levels were increased compared with a healthy reference population and were inversely correlated with Hb (r 2 ¼ 0.18, P ¼ 0.02), and positively with ferritin (r 2 ¼ 0.51, P , 0.001), but not with renal function, high-sensitivity C-reactive protein or IL-6. Erythropoietin treatment increased reticulocytes (P , 0.001) and sTfR (P , 0.001), and decreased hepcidin (P , 0.001). Baseline hepcidin levels and the magnitude of the decrease in hepcidin correlated with the increase in reticulocytes (r 2 ¼ 0.23, P ¼ 0.03) and sTfR (r 2 ¼ 0.23, P ¼ 0.03) and also with the Hb response after 6 months (r 2 ¼ 0.49, ConclusionIn this group of patients with combined heart and renal failure and anaemia, increased hepcidin levels were associated with markers of iron load and not with markers of inflammation. The (change in) hepcidin levels predicted early and long-term bone marrow response to exogenous EPO. In our group hepcidin seems to reflect iron load and response to EPO rather than inflammation and EPO resistance.--

Hepcidin in Human Iron Disorders: Diagnostic Implications

“…In HD patients on ESA, hepcidin did not predict which patients increase their hemoblobin after iron loading (17 ). As mentioned earlier, several investigators have reported a decrease in hepcidin concentrations after EPO administration (31,50,169,170 ). These findings again suggest that the erythroid demand for iron might be a more powerful regulator of hepcidin expression than inflammatory-or iron-induced hepcidin formation.…”

“…Virtually all studies on hepcidin in CKD patients revealed a strong positive relationship between hepcidin and ferritin concentrations. Some of these studies also demonstrated correlations between hepcidin and iron or transferrin saturation (169,170 ). Hepcidin in CKD also has been associated with iron-restricted erythropoiesis, as reflected by the relation of hepcidin with lower hemoglobin and/or reticulocyte counts (31,169,171 ).…”

“…Hepcidin in CKD also has been associated with iron-restricted erythropoiesis, as reflected by the relation of hepcidin with lower hemoglobin and/or reticulocyte counts (31,169,171 ). Furthermore, CRP and IL-6 were shown to be less relevant predictors in the setting of renal insufficiency (16,170,(172)(173)(174)(175). Intravenous iron administration was found not to influence hepcidin concentrations in hemodialysis (HD) patients that were withheld from iron and ESA therapy for 2 weeks (169 ), whereas it increased hepcidin in iron-naïve CKD patients (31,96 ).…”

Serum hepcidin following autologous hematopoietic cell transplantation: an illustration of the interplay of iron status, erythropoiesis and inflammation

“…5 In another study, 6 hepcidin levels at 3-5 months post transplant remained unchanged compared to (high) pre-transplant values. On the other hand, hepcidin response to erythropoietin therapy has been examined in healthy volunteers 10 or chronic kidney disease 10,11 in whom erythropoietin (EPO) elicited a rapid and persistent drop in serum hepcidin levels. Therefore, we decided to investigate the long-term kinetics of hepcidin after HCT in a group of patients participating in a clinical trial of post-transplant DA with and without intravenous iron therapy.…”

Evaluation of the Role of Hepcidin in Predicting the Therapeutic Efficacy of Erythropoiesis-Stimulating Agent Treatment in Patients of Chronic Renal Failure

“…[12] , also a study on patients with combined heart, renal failure and anemia, hepcidin levels was increased in comparison to healthy reference populations. [18], [19], [20] In this study hepcidin was negatively correlated to serum hemoglobin, serum iron and total iron binding capacity (P<0.01). (Table 3), figure (3 increased interleukin-6, high sensitive CRP may contribute to this condition.…”