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Pediatr Nephrol. 2016 May;31(5):759-68. doi: 10.1007/s00467-015-3278-0. Epub 2015 Nov 24.

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

Author information

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.

KEYWORDS:

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

PMID:
26604087
DOI:
10.1007/s00467-015-3278-0
[Indexed for MEDLINE]
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