Article

Complement regulation disorders and outcome after transplantation in children with atypical hemolytic uremic syndrome

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  • Institute of Language and Senses
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Abstract

Hemolytic uremic syndrome (HUS) is the main cause of acute renal failure in children, and the primary diagnosis in 4.5% of children in chronic renal transplantation therapy. HUS is characterized by acute renal failure, hemolytic anemia and thrombocytopenia. The typical form of HUS follows gastrointestinal infection by enterohemorrhagic Escherichia coli. 5% of all HUS cases show an atypical or recurrent course. Mutations in complement regulatory proteins play an important role in the pathogenesis of atypical HUS and in the outcome after renal transplantation. These patients have a very high risk of graft loss due to recurrence of HUS or thrombosis. Patients with HUS and no evidence of EHEC infection should be fully investigated for the known complement disorders and for autoantibodies against factor H. An accurate diagnosis of HUS based on the latest knowledge of complement dysregulation should help in predicting the risk of graft failure. New therapies are emerging and give hope for better future treatment of this severe disease. Copyrigth © Sociedad Iberoamericana de Información Científica (SIIC), 2010.

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Hemolytic uremic syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It is one of a group of conditions termed the thrombotic microangiopathies, which are characterized by prominent endothelial cell injury. It may be diarrheal-associated or atypical (aHUS). Evidence for a pathogenic role of the alternative pathway of complement was first suggested in 1974. Mutations in the complement regulatory proteins factor H, membrane cofactor protein (CD46), and factor I predispose to aHUS development. Mutations of the activating components factor B and complement C3 have also been reported. Penetrance is approximately 50%, suggesting other genetic and environmental modifiers are needed for disease expression. Identification of mutations is important owing to differences in mortality, renal survival, and outcome of renal transplantation. Current treatment is plasma infusion/exchange, but complement inhibitor therapy provides hope for the future.