Capelli John P, Kushner Harvey
Renal and Transplant Services, Our Lady of Lourdes Medical Center, Camden, NJ, USA.
Nephrol News Issues. 2006 Mar;20(3):33, 35, 39 passim.
The erythropoietic-stimulating hormone, darbepoetin alfa (Aranesp; DPO; Amgen, Thousand Oaks, California) is a long-acting agent growing in popularity as the preferred anemia management agent for patients with chronic kidney disease. Use of this drug in existing patients treated with rHu-EPO (epoetin alfa; EPO) requires conversion dosing and the potential for serious alterations in previously stable and satisfactory hemoglobin levels. This study analyzed the dosing conversion recommended by Amgen to determine if the regimen resulted in stable hemoglobin values during the conversion.
Twenty-nine stable patients on hemodialysis were selected for conversion from EPO to DPO. The dose of DPO was taken from the conversion table recommended by Amgen and based upon the patient's weekly EPO dose. The mean conversion dose was 40 mcg weekly. The patients were monitored monthly with hemoglobin, hematocrit routine chemistries, and iPTH levels according to unit policy. The dose of DPO was individually titrated to maintain the hemoglobin concentrations at target levels between 11.5 gm/dL and 13.3 gm/dL. At the end of six months, there was an analysis of the data to determine if the results warranted an adjustment in the DPO dose and if so, what the adjusted dosing factor should be.
Fifty-seven percent of the patients in the study group experienced a drop in hemoglobin levels below pre-DPO baseline levels (13.1 +/- 0.6 gm/dL) by the third month. The mean hemoglobin level dropped to 11.0 +/- 1.2 gm/dL for the entire group, representing a mean 2 +/- 1.42 gm/dL reduction. Forty-five percent of patients had a 15% to 40% drop in hemoglobin (1.9 gm/dL-5.0gm/dL). By the sixth month, patients were back to baseline hemoglobin (13.2 +/- 2.0 gm/dL). The adjusted dose at this point averaged 107 mcg weekly. Statistical analysis suggested an adjustment of 48.4 mcg to each of the Amgen recommended dose conversion values.
The current Amgen recommended DPO dose regimen for conversion from EPO resulted in a drop in hemoglobin from baseline levels in 57.2% of patients, suggesting that the current conversion table may underestimate the dose. Based upon a statistical analysis, an additional 48.4 (50) mcg to each recommended dose is needed to maintain baseline levels.
促红细胞生成激素——达贝泊汀α（商品名：阿法依泊汀；DPO；安进公司，加利福尼亚州千橡市）是一种长效药物，作为慢性肾病患者贫血管理的首选药物，其应用日益广泛。在现有的接受重组人促红细胞生成素（依泊汀α；EPO）治疗的患者中使用这种药物，需要进行剂量转换，而且可能会使之前稳定且令人满意的血红蛋白水平发生严重变化。本研究分析了安进公司推荐的剂量转换方法，以确定该方案在转换过程中是否能使血红蛋白值保持稳定。
选择29例稳定的血液透析患者从EPO转换为DPO。DPO的剂量取自安进公司推荐的转换表，并根据患者每周的EPO剂量确定。平均转换剂量为每周40微克。根据科室规定，每月对患者进行血红蛋白、血细胞比容、常规化学指标及全段甲状旁腺激素水平的监测。DPO的剂量进行个体化滴定，以将血红蛋白浓度维持在11.5克/分升至13.3克/分升的目标水平。六个月结束时，对数据进行分析，以确定结果是否需要调整DPO剂量，如果需要调整，调整后的剂量因子应该是多少。
研究组中57%的患者在第三个月时血红蛋白水平降至DPO治疗前基线水平（13.1±0.6克/分升）以下。整个组的平均血红蛋白水平降至11.0±1.2克/分升，平均降低了2±1.42克/分升。45%的患者血红蛋白下降了15%至40%（1.9克/分升 - 5.0克/分升）。到第六个月时，患者的血红蛋白恢复到基线水平（13.2±2.0克/分升）。此时调整后的剂量平均为每周107微克。统计分析表明，安进公司推荐的每个剂量转换值需调整48.4微克。
目前安进公司推荐的从EPO转换为DPO的剂量方案，导致57.2%的患者血红蛋白水平从基线下降，这表明当前的转换表可能低估了剂量。基于统计分析，每个推荐剂量需额外增加48.4（50）微克以维持基线水平。
