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.

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

BRUNATI, ANDREA;ROMAGNOLI, Renato;SALIZZONI, Mauro;
2016

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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link.springer.de/link/service/journals/00467/index.htm
Alternative; Atypical hemolytic uremic syndrome; Complement pathway; Eculizumab; Kidney transplantation; Liver transplantation; Rare diseases; Pediatrics, Perinatology and Child Health; Nephrology
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1611353
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