Anti-CFH-associated hemolytic uremic syndrome: do we still need plasma exchange?

Pediatr Nephrol. 2024 Nov;39(11):3263-3269. doi: 10.1007/s00467-024-06373-x. Epub 2024 Apr 17.

Abstract

Background: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed.

Methods: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens.

Results: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients.

Conclusions: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS.

Keywords: Atypical HUS; Children; Eculizumab; Factor H antibodies; HUS; Mycophenolate mofetil.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Atypical Hemolytic Uremic Syndrome / blood
  • Atypical Hemolytic Uremic Syndrome / diagnosis
  • Atypical Hemolytic Uremic Syndrome / drug therapy
  • Atypical Hemolytic Uremic Syndrome / immunology
  • Atypical Hemolytic Uremic Syndrome / therapy
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Child
  • Child, Preschool
  • Complement Factor H* / immunology
  • Female
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / diagnosis
  • Hemolytic-Uremic Syndrome / drug therapy
  • Hemolytic-Uremic Syndrome / immunology
  • Hemolytic-Uremic Syndrome / therapy
  • Humans
  • Immunosuppressive Agents* / therapeutic use
  • Infant
  • Male
  • Mycophenolic Acid / therapeutic use
  • Plasma Exchange*
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Treatment Outcome

Substances

  • eculizumab
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Complement Factor H
  • Autoantibodies
  • Mycophenolic Acid
  • CFH protein, human
  • Rituximab