Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective study

Pediatr Nephrol. 2018 Aug;33(8):1385-1394. doi: 10.1007/s00467-018-3903-9. Epub 2018 Mar 23.

Abstract

Background: Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results.

Methods: On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18).

Results: Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported.

Conclusions: Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken.

Keywords: Acute kidney injury; Complement; Hemolytic uremic syndrome; Pediatric.

Publication types

  • Multicenter Study

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / prevention & control
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Child, Preschool
  • Complement Activation / drug effects
  • Complement Activation / immunology
  • Complement C5 / antagonists & inhibitors
  • Complement C5 / immunology
  • Complement Inactivating Agents / pharmacology
  • Complement Inactivating Agents / therapeutic use*
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / microbiology
  • Female
  • Follow-Up Studies
  • Hemolytic-Uremic Syndrome / complications
  • Hemolytic-Uremic Syndrome / drug therapy*
  • Hemolytic-Uremic Syndrome / immunology
  • Hemolytic-Uremic Syndrome / microbiology
  • Humans
  • Infant
  • Male
  • Retrospective Studies
  • Severity of Illness Index
  • Shiga-Toxigenic Escherichia coli / isolation & purification*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • Complement Inactivating Agents
  • eculizumab