Ashby Damien R, Gale Daniel P, Busbridge Mark, Murphy Kevin G, Duncan Neill D, Cairns Tom D, Taube David H, Bloom Stephen R, Tam Frederick W K, Chapman Richard S, Maxwell Patrick H, Choi Peter
Imperial College Kidney and Transplant Institute, Hammersmith Hospital, Imperial College London, London, UK.
Kidney Int. 2009 May;75(9):976-81. doi: 10.1038/ki.2009.21. Epub 2009 Feb 11.
Hepcidin is a critical inhibitor of iron export from macrophages, enterocytes, and hepatocytes. Given that it is filtered and degraded by the kidney, its elevated levels in renal failure have been suggested to play a role in the disordered iron metabolism of uremia, including erythropoietin resistance. Here, we used a novel radioimmunoassay for hepcidin-25, the active form of the hormone, to measure its levels in renal disease. There was a significant diurnal variation of hepcidin and a strong correlation to ferritin levels in normal volunteers. In 44 patients with mild to moderate kidney disease, hepcidin levels were significantly elevated, positively correlated with ferritin but inversely correlated with the estimated glomerular filtration rate. In 94 stable hemodialysis patients, hepcidin levels were also significantly elevated, but this did not correlate with interleukin-6 levels, suggesting that increased hepcidin was not due to a general inflammatory state. Elevated hepcidin was associated with anemia, but, intriguingly, the erythropoietin dose was negatively correlated with hepcidin, suggesting that erythropoietin suppresses hepcidin levels. This was confirmed in 7 patients when hepcidin levels significantly decreased after initiation of erythropoietin treatment. Our results show that hepcidin is elevated in renal disease and suggest that higher hepcidin levels do not predict increased erythropoietin requirements.
铁调素是巨噬细胞、肠上皮细胞和肝细胞中铁输出的关键抑制剂。鉴于其可被肾脏滤过和降解，肾衰竭时其水平升高被认为在尿毒症的铁代谢紊乱中起作用，包括促红细胞生成素抵抗。在此，我们使用一种针对该激素活性形式铁调素-25的新型放射免疫分析法来检测其在肾脏疾病中的水平。正常志愿者体内铁调素存在显著的昼夜变化，且与铁蛋白水平密切相关。在44例轻至中度肾脏疾病患者中，铁调素水平显著升高，与铁蛋白呈正相关，但与估计的肾小球滤过率呈负相关。在94例稳定的血液透析患者中，铁调素水平也显著升高，但这与白细胞介素-6水平无关，表明铁调素升高并非由于全身炎症状态。铁调素升高与贫血相关，但有趣的是，促红细胞生成素剂量与铁调素呈负相关，提示促红细胞生成素可抑制铁调素水平。7例患者在开始促红细胞生成素治疗后铁调素水平显著下降，证实了这一点。我们的结果表明，肾脏疾病中铁调素水平升高，且较高的铁调素水平并不能预测促红细胞生成素需求增加。
