Liver Transplantation for aHUS: Still Needed in the Eculizumab Era?

Pediatr Nephrol. 2016 May;31(5):759-68. doi: 10.1007/s00467-015-3278-0. Epub 2015 Nov 24.

Abstract

Background: The risk of disease recurrence after a kidney transplant is high in patients with atypical hemolytic uremic syndrome (aHUS) and mutations in the complement factor H (FH) gene (CFH). Since FH is mostly produced by the liver, a kidney transplant does not correct the genetic defect. The anti-C5 antibody eculizumab prevents post-transplant aHUS recurrence, but it does not cure the disease. Combined liver-kidney transplantation has been performed in few patients with CFH mutations based on the rationale that liver replacement provides a source of normal FH.

Methods: We report the 9-year follow-up of a child with aHUS and a CFH mutation, including clinical data, extensive genetic characterization, and complement profile in the circulation and at endothelial level. The outcome of kidney and liver transplants performed separately 3 years apart are reported.

Results: The patient showed incomplete response to plasma, with relapsing episodes, progression to end-stage renal disease, and endothelial-restricted complement dysregulation. Eculizumab prophylaxis post-kidney transplant did not achieve sustained remission, leaving the child at risk of disease recurrence. A liver graft given 3 years after the kidney transplant completely abrogated endothelial complement activation and allowed eculizumab withdrawal.

Conclusions: Liver transplant may definitely cure aHUS and represents an option for patients with suboptimal response to eculizumab.

Keywords: Alternative; Atypical hemolytic uremic syndrome; Complement pathway; Eculizumab; Kidney transplantation; Liver transplantation; Rare diseases.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome / diagnosis
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Atypical Hemolytic Uremic Syndrome / therapy*
  • Cells, Cultured
  • Complement Activation / drug effects*
  • Complement Activation / genetics
  • Complement Factor H / genetics
  • Complement Inactivating Agents / therapeutic use*
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Infant
  • Kidney Transplantation*
  • Liver Transplantation*
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • complement factor H, human
  • Complement Factor H
  • eculizumab