Danielson B
Department of Medicine, University Hospital, Uppsala, Sweden.
Nephrol Dial Transplant. 1995;10 Suppl 2:69-73. doi: 10.1093/ndt/10.supp2.69.
The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
对重组人促红细胞生成素（r-HuEPO）反应有限的最常见原因是未被识别的轻至中度缺铁，这可能在治疗开始时就已存在，或者是由于新生成的红细胞对铁的利用率增加所致。慢性肾衰竭（CRF）患者的铁储备常常因胃肠道出血、血液透析过程中的失血以及采血而耗竭。铁储备的动员可能不足，尤其是在血红蛋白快速再生期间。铝过载也可能干扰胃肠道和细胞对铁的摄取。显性或未被识别的感染或炎症是反应低下的另一个常见原因，这是由于肿瘤坏死因子（TNF）、白细胞介素-1（IL-1）和干扰素-γ（IFN-γ）等细胞因子的血液浓度升高所致，这些细胞因子会抑制红细胞干细胞的增殖。较不常见的原因包括严重的继发性甲状旁腺功能亢进和骨髓瘤（化疗期间）。对r-HuEPO的反应可以通过基线纤维蛋白原（亚临床炎症的标志物）、基线转铁蛋白受体（sTfR）浓度（功能性缺铁的标志物）以及2周后的sTfR增量（红细胞生成活性早期变化的标志物）来最好地预测。
