Current treatment of atypical hemolytic uremic syndrome

• S. Kaplan Bernard

  Division of Pediatric Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, and The Perelman School of Medicine at The University of Pennsylvania

• L. Ruebner Rebecca

  Division of Pediatric Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, and The Perelman School of Medicine at The University of Pennsylvania

• M. Spinale Joann

  Division of Pediatric Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, and The Perelman School of Medicine at The University of Pennsylvania

• Copelovitch Lawrence

  Division of Pediatric Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, and The Perelman School of Medicine at The University of Pennsylvania

抄録

Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris^®, Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications. We review the conditions included under the rubric of aHUS: S. pneumoniae HUS (SpHUS), inborn errors of metabolism, and disorders of complement regulation, emphasizing their differences and similarities. We focus on the clinical features, diagnosis, and pathogenesis, and treatment of aHUS that results from mutations in genes encoding alternative complement regulators, SpHUS and HUS associated with inborn errors of metabolism. Mutations in complement genes, or antibodies to their protein products, result in unregulated activity of the alternate complement pathway, endothelial injury, and thrombotic microangiopathy (TMA). Eculizumab is a humanized monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex (C5b-9) by binding to complement protein C5a. This blocks the proinflammatory and cytolytic effects of terminal complement activation. Eculizumab use has been reported in many case reports, and retrospective and prospective clinical trials in aHUS. There have been few serious side effects and no reports of tachphylaxis or drug resistance. The results are very encouraging and eculizumab is now recognized as the treatment of choice for aHUS.

収録刊行物

• Intractable & Rare Diseases Research

  Intractable & Rare Diseases Research 3 (2), 34-45, 2014

  特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会

キーワード

• Alternate pathway of complement
• atypical hemolytic uremic syndrome
• DGPE deficiency
• eculizumab
• hemolytic uremic syndrome
• S. pneumoniae hemolytic uremic syndrome
• Cbl deficiency
• thrombotic microangiopathy

詳細情報

• CRID: 1390282680521216640
• NII論文ID: 130005008084
• DOI: 10.5582/irdr.2014.01001
• ISSN: 2186361X
• ISSN: 21863644
• Web Site: https://www.jstage.jst.go.jp/article/irdr/3/2/3_2014.01001/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015159749
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可