Complement and the atypical hemolytic uremic syndrome in children
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EDUCATIONAL REVIEW
Complement and the atypical hemolytic uremic syndrome in children Chantal Loirat & Marina Noris & Véronique Fremeaux-Bacchi
Received: 1 April 2008 / Revised: 22 April 2008 / Accepted: 22 April 2008 / Published online: 2 July 2008 # IPNA 2008
Abstract Over the past decade, atypical hemolytic uremic syndrome (aHUS) has been demonstrated to be a disorder of the regulation of the complement alternative pathway. Among approximately 200 children with the disease, reported in the literature, 50% had mutations of the complement regulatory proteins factor H, membrane cofactor protein (MCP) or factor I. Mutations in factor B and C3 have also been reported recently. In addition, 10% of children have factor H dysfunction due to anti-factor H antibodies. Early age at onset appears as characteristic of factor H and factor I mutated patients, while MCPassociated HUS is not observed before age 1 year. Low C3 level may occur in patients with factor H and factor I mutation, while C3 level is generally normal in MCPmutated patients. Normal plasma factor H and factor I levels do not preclude the presence of a mutation in these genes. The worst prognosis is for factor H-mutated patients,
C. Loirat Assistance Publique - Hôpitaux de Paris, Université Paris 7, Hôpital Robert Debré, Pediatric Nephrology, Paris, France M. Noris Clinical Research Center for Rare Diseases Aldo e Cele Dacco, Mario Negri Institute for Pharmacological Research, Ranica, Italy V. Fremeaux-Bacchi Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Biological Immunology Department, Paris, France C. Loirat (*) Service de Néphrologie, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France e-mail: [email protected]
as 60% die or reach end-stage renal disease (ESRD) within the first year after onset of the disease. Patients with mutations in MCP have a relapsing course, but no patient has ever reached ESRD in the first year of the disease. Half of the patients with factor I mutations have a rapid evolution to ESRD, but half recover. Early intensive plasmatherapy appears to have a beneficial effect, except in MCP-mutated patients. There is a high risk of graft loss for HUS recurrence or thrombosis in all groups except the MCP-mutated group. Recent success of liver–kidney transplantation combined with plasmatherapy opens this option for patients with mutations of factors synthesized in the liver. New therapies such as factor H concentrate or complement inhibitors offer hope for the future. Keywords Hemolytic uremic syndrome . Alternative pathway of complement . C3 . Complement factor H . Factor I . Factor B . Membrane cofactor protein . Plasma infusion . Plasma exchange . Transplantation
Introduction Hemolytic uremic syndrome (HUS) is characterized by the triad of hemolytic anemia with fragmented erythrocytes, thrombocytopenia and acute renal failure. The underlying histological lesion is thrombotic microangiopathy. In children, the most frequent form (90% of patients), called typical or post-diarrheal (D+)
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