Besarab A
Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
Am J Nephrol. 1990;10 Suppl 2:2-6. doi: 10.1159/000168208.
The anemia associated with renal failure has been studied for over 150 years. It results primarily from inadequate production of erythropoietin such that plasma levels in dialysis patients are only 25% of those expected for the degree of anemia. Shortened red call survival, iron and other nutritional deficiencies, and uremic inhibitors have a secondary and minor role. Recombinant human erythropoietin (rHuEPO) is now used to treat this anemia. It is heavily sialated, which permits its circulation long enough to act on the bone marrow where, in concert with other growth factors, it commits progenitor cells to the erythroid cell pathway. Major issues related to clinical use of rHuEPO are dosage, resistance, and cost. Pharmacokinetic studies predict significant weekly dose reductions (and therefore cost savings) using the subcutaneous route compared to the intravenous route permitting more patients to be treated optimally. Biological heterogeneity and not hyperparathyroidism or aluminum overload accounts for most instances in which more than 450 U/kg/wk of rHuEPO is required.
与肾衰竭相关的贫血已经被研究了150多年。它主要是由于促红细胞生成素产生不足所致，以至于透析患者的血浆水平仅为贫血程度预期水平的25%。红细胞存活时间缩短、铁及其他营养缺乏以及尿毒症抑制剂起次要和较小的作用。重组人促红细胞生成素（rHuEPO）现在用于治疗这种贫血。它高度唾液酸化，这使其能够循环足够长的时间作用于骨髓，在骨髓中，它与其他生长因子协同作用，使祖细胞进入红细胞生成途径。与rHuEPO临床应用相关的主要问题是剂量、耐药性和成本。药代动力学研究预测，与静脉途径相比，皮下途径每周剂量可显著降低（从而节省成本），使更多患者能够得到最佳治疗。大多数需要超过450 U/kg/周的rHuEPO的情况是由生物学异质性而非甲状旁腺功能亢进或铝过载导致的。
