Rosanna Coppo1, Roberto Bonaudo1, R Licia Peruzzi1, Alessandro Amore1, Andrea Brunati2, Renato Romagnoli2, Mauro Salizzoni2, Miriam Galbusera3,4, Eliana Gotti5, Erica Daina3, Marina Noris6, Giuseppe Remuzzi3,4,5,7. 1. Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Turin and Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy. 2. Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, Molinette Hospital, University of Turin , Turin, Italy. 3. Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy. 4. Centro Anna Maria Astori, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Science and Technology Park Kilometro Rosso, Bergamo, Italy. 5. Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. 6. Clinical Research Center for Rare Diseases "Aldo e Cele Daccò", IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Villa Camozzi, 3-24020, Ranica (Bergamo), Italy. marina.noris@marionegri.it. 7. Department of Biomedical Sciences of Health, University of Milan, Milan, Italy.
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.
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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