An international consensus approach to the management of atypical hemolytic uremic syndrome in children

Pediatr Nephrol. 2016 Jan;31(1):15-39. doi: 10.1007/s00467-015-3076-8. Epub 2015 Apr 11.

Abstract

Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

Keywords: Anti-factor H antibody; Atypical hemolytic uremic syndrome; Children; Combined liver–kidney transplantation; Complement; Eculizumab; Hemolytic uremic syndrome; Kidney transplantation; Plasma exchange; Plasma infusion; Thrombotic microangiopathy.

Publication types

  • Practice Guideline
  • Review

MeSH terms

  • Adolescent
  • Age Factors
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Atypical Hemolytic Uremic Syndrome / diagnosis
  • Atypical Hemolytic Uremic Syndrome / epidemiology
  • Atypical Hemolytic Uremic Syndrome / immunology
  • Atypical Hemolytic Uremic Syndrome / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Complement Activation / drug effects
  • Consensus
  • Cooperative Behavior
  • Drug Monitoring
  • Humans
  • Immunologic Factors / therapeutic use
  • Infant
  • Infant, Newborn
  • International Cooperation
  • Kidney Transplantation
  • Liver Transplantation
  • Monitoring, Immunologic
  • Nephrology / standards*
  • Patient Selection
  • Plasma Exchange
  • Predictive Value of Tests
  • Risk Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • eculizumab