Liver transplantation for aHUS: still needed in the eculizumab era?
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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.
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.
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.
Liver transplant may definitely cure aHUS and represents an option for patients with suboptimal response to eculizumab.
KeywordsAtypical hemolytic uremic syndrome Eculizumab Kidney transplantation Liver transplantation Complement pathway Alternative Rare diseases
The authors are deeply grateful to Dr. Piero Ruggenenti for clinical advice and helpful discussion; to Dott. Pier Luigi Calvo for his invaluable contribution to the clinical management both immediately before and after liver transplant; to Drs. Caterina Mele, Rossella Piras, Ramona Maranta, and Marta Alberti for performing the genetic analysis; to Dr Serena Bettoni for measuring plasma SC5b-9 levels and CH50; to Dr Elisabetta Valoti for performing anti-FH autoantibody and multiple ligation probe amplification tests; to Sara Gastoldi for contributing to the ex vivo test of serum-induced C5b-9 deposits; to Dr. Michael Kirschfink (University of Heidelberg, Germany) for evaluating eculizumab levels. We also wish to thank Dr. Kerstin Mierke for English editing and Manuela Passera for secretary assistance.
Compliance with ethical standards
The parents of the patient provided written informed consent to the analyses and the procedures reported in this paper.
Source of funding
This study was partially supported by Fondazione ART per la Ricerca sui Trapianti ART ONLUS (Milan, Italy) and by the European Union Seventh Framework Programme FP7-EURenOmics project number 305608.
Conflict of interest
The authors declare that they have no conflict of interest.
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