Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Kidney Int. 2017 Nov;92(5):1261-1271. doi: 10.1016/j.kint.2017.04.028. Epub 2017 Jul 24.

Abstract

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.

Keywords: acute kidney injury; atypical hemolytic uremic syndrome; complement; factor H autoantibodies; thrombotic microangiopathy.

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Atypical Hemolytic Uremic Syndrome / blood
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Atypical Hemolytic Uremic Syndrome / immunology*
  • Atypical Hemolytic Uremic Syndrome / therapy
  • Autoantibodies / blood*
  • Child
  • Child, Preschool
  • Complement Factor H / immunology
  • Complement System Proteins / analysis
  • Complement System Proteins / genetics
  • Female
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Immunosuppression Therapy / methods
  • Infant
  • Ireland
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation*
  • Male
  • Plasma Exchange
  • Recurrence
  • Renal Dialysis
  • Retrospective Studies
  • United Kingdom

Substances

  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • CFH protein, human
  • Complement Factor H
  • Complement System Proteins
  • eculizumab