Pediatric Nephrology

, Volume 26, Issue 1, pp 41–57 | Cite as

aHUS caused by complement dysregulation: new therapies on the horizon

  • Aoife M. Waters
  • Christoph Licht
Educational Review


Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5–10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS.


Atypical hemolytic uremic syndrome Defective complement regulation Plasma therapy Eculizumab 


Supplementary material

467_2010_1556_MOESM1_ESM.doc (180 kb)
Supplementary Materials (DOC 179 kb)


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Copyright information

© IPNA 2010

Authors and Affiliations

  1. 1.Department of NephrologyGreat Ormond Street HospitalLondonUK
  2. 2.University College London, Institute of Child HealthLondonUK
  3. 3.Division of NephrologyHospital for Sick ChildrenTorontoCanada
  4. 4.Department of PaediatricsUniversity of TorontoTorontoCanada

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