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.
| Original language | English |
|---|---|
| Pages (from-to) | 759-768 |
| Journal | Pediatric Nephrology |
| Volume | 31 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- Alternative
- Atypical hemolytic uremic syndrome
- Complement pathway
- Eculizumab
- Kidney transplantation
- Liver transplantation
- Rare diseases
ASJC Scopus subject areas
- Nephrology
- Pediatrics, Perinatology, and Child Health
Cite this
Liver transplantation for aHUS : still needed in the eculizumab era? / 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.
In: Pediatric Nephrology, Vol. 31, 2016, p. 759-768.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Liver transplantation for aHUS
T2 - still needed in the eculizumab era?
AU - Coppo, Rosanna
AU - Bonaudo, Roberto
AU - Peruzzi, R. Licia
AU - Amore, Alessandro
AU - Brunati, Andrea
AU - Romagnoli, Renato
AU - Salizzoni, Mauro
AU - Galbusera, Miriam
AU - Gotti, Eliana
AU - Daina, Erica
AU - Noris, Marina
AU - Remuzzi, Giuseppe
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Alternative
KW - Atypical hemolytic uremic syndrome
KW - Complement pathway
KW - Eculizumab
KW - Kidney transplantation
KW - Liver transplantation
KW - Rare diseases
UR - http://www.scopus.com/inward/record.url?scp=84948138781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948138781&partnerID=8YFLogxK
U2 - 10.1007/s00467-015-3278-0
DO - 10.1007/s00467-015-3278-0
M3 - Article
VL - 31
SP - 759
EP - 768
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
ER -