De Palo Tommaso, Giordano Mario, Palumbo Fabrizio, Bellantuono Rosa, Messina Giovanni, Colella Vincenzo, Caringella Angela D
Pediatric Nephrology and Dialysis Unit, Children's Hospital Giovanni XXIII, Bari, Italy.
Pediatr Nephrol. 2004 Mar;19(3):337-40. doi: 10.1007/s00467-003-1364-1. Epub 2004 Jan 27.
Darbepoietin alfa (NESP) is a new long-acting erythropoietin, with a half-life 3 times longer than the old epoietins. In the present study, we evaluated the efficacy of NESP in a group of children on hemodialysis. Seven children, five male and two female, with a mean age of 11.5 +/- 3 years and a mean weight of 34.1 +/- 11 kg, were enrolled in the study. All had been treated for at least 6 months with epoietin alfa at a mean dose of 106 +/- 76 IU/kg 3 times/week i.v. They were then given NESP at a mean dose of 1.59 +/- 1.19 microg/kg once a week i.v., according to the suggested conversion index (weekly epoietin alfa dose/200=weekly NESP dose). Anemia was evaluated at the end of a dialysis session. This was especially important for children less compliant with water restriction. Serum ferritin and percentage transferrin saturation (TSAT) were also monitored, as were dialysis efficacy (Kt/V), blood pressure, and heparin requirements. Before starting the new treatment, all patients had an adequate mean hemoglobin (Hb) level (11.19 +/- 1.7 g/dl) and an adequate iron status (TSAT 24.2 +/- 11.5, serum ferritin 220 +/- 105 mg/dl). Five of the seven patients were also treated with intravenous ferric gluconate (10-20 mg/kg per week). Six children were on antihypertensive treatment. After the 1st month of treatment, we observed an excessive increase in Hb, 12.3 +/- 1.7 g/dl, (P<0.05), with severe hypertension in the youngest two patients (Hb>13 g/dl). A short discontinuation of the medication, followed by restarting at a decreased dosage, allowed us to continue with the treatment. At the 2nd month of follow-up, a mean plasma Hb level of 12.2 +/- 1.2 g/dl was observed, with a NESP mean dose of 0.79 +/- 0.4 microg/kg per week. Steady state was reached at 3 months, with a mean Hb of 11.8 +/- 1.4 g/dl and a mean NESP dose of 0.51 +/- 0.18 microg/kg per week (P<0.05). These results persisted at 6 months of follow-up; only one child had a persistent increase in platelet level (373,000 vs. 555,000). Dialysis efficiency and heparin requirements during dialysis did not change significantly. The high efficacy of NESP allowed a consistent reduction in dosage. The suggested conversion index does not appear to be correct for pediatric patients. Our experience suggests that in this population the correct dose could be 0.25-0.75 microg/kg per week. Hypertension was the only major side effect reported. The influence of NESP on platelet proliferation needs to be further investigated. The single weekly administration of NESP could be effective and beneficial for both patients and clinicians.
达贝泊汀α（NESP）是一种新型长效促红细胞生成素，其半衰期比旧的促红细胞生成素长3倍。在本研究中，我们评估了NESP对一组接受血液透析儿童的疗效。7名儿童（5名男性和2名女性）参与了该研究，他们的平均年龄为11.5±3岁，平均体重为34.1±11千克。所有儿童均接受促红细胞生成素α治疗至少6个月，平均剂量为106±76国际单位/千克，静脉注射，每周3次。然后根据建议的换算指数（每周促红细胞生成素α剂量/200 =每周NESP剂量），给予他们平均剂量为1.59±1.19微克/千克的NESP，静脉注射，每周1次。在透析结束时评估贫血情况。这对不太遵守水限制的儿童尤为重要。还监测了血清铁蛋白和转铁蛋白饱和度百分比（TSAT），以及透析疗效（Kt/V）、血压和肝素需求量。在开始新治疗前，所有患者的平均血红蛋白（Hb）水平充足（11.19±1.7克/分升），铁状态良好（TSAT 24.2±11.5，血清铁蛋白220±105毫克/分升）。7名患者中有5名还接受了葡萄糖酸铁静脉注射治疗（每周10 - 20毫克/千克）。6名儿童接受抗高血压治疗。治疗第1个月后，我们观察到Hb过度升高，达到12.3±1.7克/分升（P<0.05），最年幼的两名患者出现严重高血压（Hb>13克/分升）。短暂停药，随后以降低的剂量重新开始治疗，使我们能够继续进行治疗。在随访的第2个月，观察到平均血浆Hb水平为12.2±1.2克/分升，NESP平均剂量为0.79±0.4微克/千克/周。3个月时达到稳态，平均Hb为11.8±1.4克/分升，NESP平均剂量为0.51±0.18微克/千克/周（P<0.05）。这些结果在随访6个月时持续存在；只有一名儿童的血小板水平持续升高（从373,000升至555,000）。透析效率和透析期间的肝素需求量没有显著变化。NESP的高效能使得剂量得以持续减少。建议的换算指数对儿科患者似乎并不正确。我们的经验表明，在这一人群中，正确剂量可能为每周0.25 - 0.75微克/千克。高血压是报告的唯一主要副作用。NESP对血小板增殖的影响需要进一步研究。NESP每周一次的单次给药对患者和临床医生可能都是有效且有益的。
