Division of Nephrology, CHU Sainte-Justine, Montréal, Québec, Canada.
Pediatr Nephrol. 2011 Apr;26(4):621-4. doi: 10.1007/s00467-010-1719-3. Epub 2010 Dec 15.
Atypical hemolytic uremic syndrome (aHUS) is a rare, chronic, life-threatening disease due to complement dysregulation. The use of early-onset plasma therapy is recommended, but optimal long-term treatment regimen is not well defined. Eculizumab, a monoclonal humanized anti-C5 antibody, has shown success in patients with aHUS. We report a 7-year-old girl with aHUS associated with factor H mutations successfully treated with eculizumab. Weekly plasma infusion (PI) of 25-30 ml/kg with short-term intensified PI during aHUS exacerbations was effective for 4.3 years. Progressive mild renal failure (stage 2) was attributed to chronic glomerular lesions. Subsequently, she exhibited aHUS exacerbation unresponsive to intensified PI. Eculizumab was initiated at 600 mg, resulting in immediate and complete inhibition of terminal complement activation. During the week following treatment, we observed a complete reversal of aHUS activity. She has been receiving 600 mg eculizumab every 2 weeks for the last 12 months. She had no aHUS exacerbation, and serum creatinine level returned to normal. In this patient, eculizumab led to control of PI-resistant aHUS exacerbation and chronic microangiopathic hemolytic activity. Clinical trials are ongoing to assess the safety and efficacy of this drug in the management of aHUS.
非典型溶血尿毒症综合征（aHUS）是一种罕见的、慢性的、危及生命的疾病，其发病机制与补体失调有关。建议早期应用血浆置换治疗，但尚未明确最佳的长期治疗方案。依库珠单抗是一种靶向补体 C5 的人源化单克隆抗体，已被证实可成功治疗 aHUS 患者。我们报告了一例伴因子 H 突变的 aHUS 患儿，经依库珠单抗治疗后获得成功。在 aHUS 加重期间，我们采用每周 25-30ml/kg 的血浆输注（PI）联合短期强化 PI，治疗有效持续了 4.3 年。进展性轻度肾功能衰竭（Ⅱ期）归因于慢性肾小球病变。此后，患儿出现了强化 PI 治疗无效的 aHUS 加重。依库珠单抗起始剂量为 600mg，可立即完全抑制末端补体激活。治疗后的第 1 周，我们观察到 aHUS 活动完全逆转。此后，患儿每 2 周接受 600mg 依库珠单抗治疗，至今已持续 12 个月。患儿未再发生 aHUS 加重，血清肌酐水平恢复正常。在该患者中，依库珠单抗控制了 PI 抵抗的 aHUS 加重和慢性微血管溶血性活性。目前正在进行临床试验，以评估该药在 aHUS 治疗中的安全性和疗效。
