Department of Pediatrics, Barzilay, University Medical Center, Ashkelon, Israel.
Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Paediatr Drugs. 2023 Mar;25(2):193-202. doi: 10.1007/s40272-022-00555-6. Epub 2023 Jan 13.
Atypical hemolytic uremic syndrome is a thrombotic microangiopathy characterized by hemolysis, thrombocytopenia, and acute kidney injury, usually caused by alternative complement system overactivation due to pathogenic genetic variants or antibodies to components or regulatory factors in this pathway. Previously, a lack of effective treatment for this condition was associated with mortality, end-stage kidney disease, and the risk of disease recurrence after kidney transplantation. Plasma therapy has been used for atypical hemolytic uremic syndrome treatment with inconsistent results. Complement-blocking treatment changed the outcome and prognosis of patients with atypical hemolytic uremic syndrome. Early administration of eculizumab, a monoclonal C5 antibody, leads to improvements in hematologic, kidney, and systemic manifestations in patients with atypical hemolytic uremic syndrome, even with apparent dialysis dependency. Pre- and post-transplant use of eculizumab is effective in the prevention of atypical hemolytic uremic syndrome recurrence. Evidence on eculizumab use in secondary hemolytic uremic syndrome cases is controversial. Recent data favor the restrictive use of eculizumab in carefully selected atypical hemolytic uremic syndrome cases, but close monitoring for relapse after drug discontinuation is emphasized. Prophylaxis for meningococcal infection is important. The long-acting C5 monoclonal antibody ravulizumab is now approved for atypical hemolytic uremic syndrome treatment, enabling a reduction in the dosing frequency and improving the quality of life in patients with atypical hemolytic uremic syndrome. New strategies for additional and novel complement blockage medications in atypical hemolytic uremic syndrome are under investigation.
非典型溶血尿毒综合征是一种血栓性微血管病，其特征为溶血、血小板减少和急性肾损伤，通常由替代补体系统过度激活引起，原因是致病性遗传变异或针对该途径中成分或调节因子的抗体。以前，由于缺乏有效的治疗方法，该病与死亡率、终末期肾病以及肾移植后疾病复发的风险相关。血浆疗法已用于治疗非典型溶血尿毒综合征，但疗效不一。补体阻断治疗改变了非典型溶血尿毒综合征患者的结局和预后。早期给予单克隆 C5 抗体依库珠单抗可改善非典型溶血尿毒综合征患者的血液学、肾脏和全身表现，即使存在明显的透析依赖。在移植前和移植后使用依库珠单抗可有效预防非典型溶血尿毒综合征复发。关于依库珠单抗在继发性溶血尿毒综合征病例中的应用的证据存在争议。最近的数据倾向于在仔细选择的非典型溶血尿毒综合征病例中限制使用依库珠单抗，但强调停药后密切监测疾病复发。预防脑膜炎奈瑟菌感染很重要。长效 C5 单克隆抗体拉维珠单抗现已获准用于治疗非典型溶血尿毒综合征，可减少给药频率并提高非典型溶血尿毒综合征患者的生活质量。正在研究用于非典型溶血尿毒综合征的其他和新型补体阻断药物的新策略。
