Department of Internal Medicine, Meander MC Amersfoort, Amersfoort, The Netherlands.
Eur J Heart Fail. 2010 Sep;12(9):943-50. doi: 10.1093/eurjhf/hfq099. Epub 2010 Jul 3.
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.
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 (r(2) = 0.18, P = 0.02), and positively with ferritin (r(2) = 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) = 0.23, P = 0.03) and sTfR (r(2) = 0.23, P = 0.03) and also with the Hb response after 6 months (r(2) = 0.49, P = 0.001).
In 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.
促红细胞生成素（EPO）抵抗是导致心肾衰竭患者贫血的一个重要原因，与死亡率升高有关。本研究的假设是外源性 EPO 可降低铁调素水平，而 EPO 治疗后铁调素水平的降低与骨髓反应有关。
在 EPOCARES 试验中，肾小球滤过率为 20-70mL/min 的肾衰竭、心力衰竭和贫血患者被随机分为接受 50IU/kg/周 EPO（n=20）或不接受 EPO（n=13）治疗。在基线和治疗期间测量血红蛋白（Hb）、铁调素-25、铁蛋白、网织红细胞、血清转铁蛋白受体（sTfR）、白细胞介素-6（IL-6）和高敏 C 反应蛋白。铁调素-25 采用弱阳离子交换色谱/基质辅助激光解吸电离飞行时间质谱法测定。与健康参考人群相比，基线铁调素水平升高，与 Hb 呈负相关（r²=0.18，P=0.02），与铁蛋白呈正相关（r²=0.51，P<0.001），但与肾功能、高敏 C 反应蛋白或 IL-6 无关。EPO 治疗增加了网织红细胞（P<0.001）和 sTfR（P<0.001），并降低了铁调素（P<0.001）。基线铁调素水平和铁调素降低的幅度与网织红细胞（r²=0.23，P=0.03）和 sTfR（r²=0.23，P=0.03）的增加以及 6 个月后 Hb 的反应相关（r²=0.49，P=0.001）。
在这组合并心肾衰竭和贫血的患者中，铁调素水平升高与铁负荷标志物相关，而与炎症标志物无关。（变化）铁调素水平预测了外源性 EPO 对早期和长期骨髓反应。在我们的研究组中，铁调素似乎反映了铁负荷和对 EPO 的反应，而不是炎症和 EPO 抵抗。
