Liver transplantation for aHUS: still needed in the eculizumab era?

Rosanna Coppo, Roberto Bonaudo, R. Licia Peruzzi, Alessandro Amore, Andrea Brunati, Renato Romagnoli, Mauro Salizzoni, Miriam Galbusera, Eliana Gotti, Erica Daina, Marina Noris, Giuseppe Remuzzi

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)759-768
JournalPediatric Nephrology
Volume31
DOIs
Publication statusPublished - 2016

Fingerprint

Liver Transplantation
Transplants
Complement Factor H
Kidney
Liver
Recurrence
Mutation
eculizumab
Atypical Hemolytic Uremic Syndrome
Complement Activation
Chronic Kidney Failure
Anti-Idiotypic Antibodies
Transplantation
Genes

Keywords

  • Alternative
  • Atypical hemolytic uremic syndrome
  • Complement pathway
  • Eculizumab
  • Kidney transplantation
  • Liver transplantation
  • Rare diseases

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Coppo, R., Bonaudo, R., Peruzzi, R. L., Amore, A., Brunati, A., Romagnoli, R., ... Remuzzi, G. (2016). Liver transplantation for aHUS: still needed in the eculizumab era? Pediatric Nephrology, 31, 759-768. https://doi.org/10.1007/s00467-015-3278-0

Liver transplantation for aHUS : still needed in the eculizumab era? / Coppo, Rosanna; Bonaudo, Roberto; Peruzzi, R. Licia; Amore, Alessandro; Brunati, Andrea; Romagnoli, Renato; Salizzoni, Mauro; Galbusera, Miriam; Gotti, Eliana; Daina, Erica; Noris, Marina; Remuzzi, Giuseppe.

In: Pediatric Nephrology, Vol. 31, 2016, p. 759-768.

Research output: Contribution to journalArticle

Coppo, R, Bonaudo, R, Peruzzi, RL, Amore, A, Brunati, A, Romagnoli, R, Salizzoni, M, Galbusera, M, Gotti, E, Daina, E, Noris, M & Remuzzi, G 2016, 'Liver transplantation for aHUS: still needed in the eculizumab era?', Pediatric Nephrology, vol. 31, pp. 759-768. https://doi.org/10.1007/s00467-015-3278-0
Coppo R, Bonaudo R, Peruzzi RL, Amore A, Brunati A, Romagnoli R et al. Liver transplantation for aHUS: still needed in the eculizumab era? Pediatric Nephrology. 2016;31:759-768. https://doi.org/10.1007/s00467-015-3278-0
Coppo, Rosanna ; Bonaudo, Roberto ; Peruzzi, R. Licia ; Amore, Alessandro ; Brunati, Andrea ; Romagnoli, Renato ; Salizzoni, Mauro ; Galbusera, Miriam ; Gotti, Eliana ; Daina, Erica ; Noris, Marina ; Remuzzi, Giuseppe. / Liver transplantation for aHUS : still needed in the eculizumab era?. In: Pediatric Nephrology. 2016 ; Vol. 31. pp. 759-768.
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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.",
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AU - Brunati, Andrea

AU - Romagnoli, Renato

AU - Salizzoni, Mauro

AU - Galbusera, Miriam

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AU - Noris, Marina

AU - Remuzzi, Giuseppe

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AB - 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.

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