title: Podocyte dysfunction in atypical haemolytic uraemic syndrome.
abstract: Genetic or autoimmune defects that lead to dysregulation of the alternative pathway of complement have been associated with the development of atypical haemolytic uraemic syndrome (aHUS), which is characterized by thrombocytopenia, haemolytic anaemia and acute kidney injury. The relationship between aHUS, podocyte dysfunction and the resultant proteinuria has not been adequately investigated. However, the report of mutations in diacylglycerol kinase ε (DGKE) as a cause of recessive infantile aHUS characterized by proteinuria, highlighted podocyte dysfunction as a potential complication of aHUS. DGKE deficiency was originally thought to trigger aHUS through pathogenetic mechanisms distinct from complement dysregulation; however, emerging findings suggest an interplay between DGKE and complement systems. Podocyte dysfunction with nephrotic-range proteinuria can also occur in forms of aHUS associated with genetic or autoimmune complement dysregulation without evidence of DGKE mutations. Furthermore, proteinuric glomerulonephritides can be complicated by aHUS, possibly as a consequence of podocyte dysfunction inducing endothelial injury and prothrombotic abnormalities.
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò", Via Camozzi 3, 24020, Ranica, Bergamo, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò", Via Camozzi 3, 24020, Ranica, Bergamo, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mele
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò", Via Camozzi 3, 24020, Ranica, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome / Q000209:etiology* / Q000235:genetics; D003165:Complement System Proteins; D019852:Diacylglycerol Kinase / Q000235:genetics; D006801:Humans; D009154:Mutation; D050199:Podocytes / Q000502:physiology*
chemical_list: D003165:Complement System Proteins; D019852:Diacylglycerol Kinase