Children's Hospital, Louisiana State University Health Science Center, New Orleans, Louisiana 70118, USA.
Kidney Int. 2011 Sep;80(5):464-74. doi: 10.1038/ki.2011.179. Epub 2011 Jun 22.
Routine administration of erythropoietin (EPO)-stimulating agents (ESAs) for the control of anemia has improved the quality of life of subjects with chronic kidney disease (CKD). However, a wide variation in individual response to ESA is often observed. The reasons for EPO resistance include demographic variables such as age and gender distribution, morbidity pattern, and modality of dialysis. Despite suggestions by observational data, there is no biological characteristic that puts children at a disadvantage for adequate response to ESA. On the contrary, children possess a superior capacity for red cell production, including extramedullary erythropoiesis. The reasons for larger requirement of ESA in children (than in adults) are greater inflammatory burden, disproportionate blood loss, and greater EPO dosing by pediatric physicians. To minimize the harmful (including fatal) consequences of EPO resistance, surveillance programs must replenish nutrient (for example, iron and folate) stores, minimize oxidative hemolysis, control hyperparathyroidism, avoid catheter infection, and optimize uremic clearance. This clinical approach is justified by the inadequacy of laboratory diagnosis of pertinent etiological factors. Indeed, the best proof for functional nutrient deficiency is often a therapeutic trial. Finally, there are upcoming therapeutic agents that exploit the capacity for an endogenous EPO synthesis in CKD subjects, and may therefore minimize the off-target effect of excess dosages.
常规给予促红细胞生成素（EPO）刺激剂（ESA）以控制贫血症提高了慢性肾脏病（CKD）患者的生活质量。然而，个体对 ESA 的反应存在广泛的差异。EPO 抵抗的原因包括年龄和性别分布等人口统计学变量、发病模式和透析方式等。尽管观察性数据表明存在这种情况，但没有生物学特征表明儿童对 ESA 的反应不足。相反，儿童具有更高的红细胞生成能力，包括骨髓外红细胞生成。儿童（比成人）对 ESA 的需求量更大的原因是炎症负担更大、失血量不成比例，以及儿科医生给予的 EPO 剂量更大。为了最大限度地减少 EPO 抵抗的有害（包括致命）后果，必须监测方案以补充营养（例如铁和叶酸）储存、减少氧化溶血、控制甲状旁腺功能亢进症、避免导管感染并优化尿毒症清除率。这种临床方法是基于对相关病因因素的实验室诊断不足的考虑。事实上，功能性营养缺乏的最佳证据通常是治疗试验。最后，有一些新的治疗药物利用 CKD 患者内源性 EPO 合成的能力，因此可能最大限度地减少过量剂量的脱靶效应。
