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Atypical Hemolytic Uremic Syndrome

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Pediatric Kidney Disease

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Abstract

Atypical hemolytic uremic syndrome (aHUS) has been demonstrated during the last decade to be mostly a disease of complement overactivation. Mutations in the genes of factor H, factor I, membrane cofactor protein, C3, factor B and thrombomodulin and acquired autoantibodies against factor H have been identified. Most complement mutations are heterozygous with an autosomal dominant transmission and incomplete penetrance of the disease. Additional genetic susceptibility factors and precipitating events or triggers appear required for the disease to manifest. Genotype-phenotype correlations have shown that the prognosis of aHUS involving native kidneys and the outcome after kidney transplantation largely depend on the genetic background. Plasma exchanges were the mainstay of treatment of aHUS until 2009, with a high rate of catheter-related complications in children. Complement blockade therapy by eculizumab has revolutionized the hitherto dismal prognosis of aHUS and the management of patients. However, the genetic background of aHUS is not yet fully elucidated and mutations in the gene of diacylglycerol kinase ε, a non complement –related protein, have been recently identified in children with an autosomal recessive form of aHUS, suggesting aHUS can also be complement-independent.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, University Hospital Robert Debre, 48 Boulevard Serurier, Paris, 75019, France

    Chantal Loirat

  2. Laboratoire d’Immunologie, Hopital Europeen Georges Pompidou, 20 Rue Leblanc, 75015, Paris, France

    Véronique Frémeaux-Bacchi

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  1. Chantal Loirat
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Correspondence to Chantal Loirat .

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  1. Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Denis F. Geary

  2. Division of Pediatric Nephrology, University of Heidelberg, Heidelberg, Germany

    Franz Schaefer

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Loirat, C., Frémeaux-Bacchi, V. (2016). Atypical Hemolytic Uremic Syndrome. In: Geary, D., Schaefer, F. (eds) Pediatric Kidney Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-52972-0_24

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