TY - JOUR
T1 - Hepcidin-25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease/chronic heart failure patients
AU - van der Putten, Karien
AU - Jie, Kim E.
AU - van den Broek, Daan
AU - Kraaijenhagen, Rob J.
AU - Laarakkers, Coby
AU - Swinkels, Dorine W.
AU - Braam, Branko
AU - Gaillard, Carlo A.
N1 - M1 - 9
PY - 2010/9
Y1 - 2010/9
N2 - Aims Erythropoietin (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 results and In 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 = 20) or not (n = 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 (r2 = 0.18, P = 0.02), and positively with ferritin (r2 = 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 (r2 = 0.23, P = 0.03) and sTfR (r2 = 0.23, P = 0.03) and also with the Hb response after 6 months (r2 = 0.49, P = 0.001). 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. © 2010 The Author.
AB - Aims Erythropoietin (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 results and In 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 = 20) or not (n = 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 (r2 = 0.18, P = 0.02), and positively with ferritin (r2 = 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 (r2 = 0.23, P = 0.03) and sTfR (r2 = 0.23, P = 0.03) and also with the Hb response after 6 months (r2 = 0.49, P = 0.001). 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. © 2010 The Author.
KW - Anaemia
KW - Chronic kidney disease
KW - Heart failure
KW - Hepcidin
KW - Inflammation
KW - Iron
UR - http://www.scopus.com/inward/record.url?scp=77955957335&partnerID=8YFLogxK
U2 - 10.1093/eurjhf/hfq099
DO - 10.1093/eurjhf/hfq099
M3 - Article
C2 - 20601671
SN - 1388-9842
VL - 12
SP - 943
EP - 950
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 9
ER -