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

• Published in: Pediatric nephrology (Berlin, West) Vol. 31; no. 5; pp. 759 - 768
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2016; Springer Nature B.V
• Subjects: Antibodies; 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; Disease prevention; DNA Mutational Analysis; Genes; Genetic Predisposition to Disease; Heredity; Humans; Infant; Kidney diseases; Kidney Transplantation; Kidney transplants; Liver; Liver Transplantation; Male; Medicine; Medicine & Public Health; Mutation; Nephrology; Original Article; Patients; Pediatrics; Pedigree; Phenotype; Rare diseases; Treatment Outcome; Urology; Italy; Rare diseases; Alternative; Atypical hemolytic uremic syndrome; Eculizumab; Complement pathway; Kidney transplantation; Liver transplantation
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-015-3278-0

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.