[Hemolytic uremic syndrome].
Hemolytic Uremic Syndrome (HUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytope-nia, and acute renal failure. HUS is most commonly triggered by Shiga-like toxin (Stx)-producing bacteria (Stx-HUS). Non-Shiga toxin-associated HUS (non-Stx-HUS) affects a heterogeneous group of patients in whom an infection by Stx-producing bacteria can be excluded as cause of the disease. It can be sporadic or familial. Biochemical evidence suggested that alterations in the complement system play an important role in the pathological mechanisms of non-Stx-HUS. Subsequently, genetic studies have shown that the disease depends on the deficiency or abnormalities in complement regulatory proteins of the alternative pathway. About 30% of the patients have mutations in the gene encoding factor H (CFH); CFH is a protein that inhibits the activation of the alternative pathway of the complement system. More recent observations have also shown the involvement of genes that encode Membrane Cofactor Protein (MCP) and factor I (CFI). Genetic studies can be useful to improve therapeutic approach. Plasma infusion or plasma exchange are helpful treatments for patients with alterations in CFH or CFI, which are plasma proteins. On the other hand, plasma treatment in patients with alterations in MCP, a membrane-bound protein, does not impact the outcome significantly. Kidney transplantation outcome is favorable in patients with MCP mutations, whereas the outcome is poor in patients with CFH and CFI mutations due to disease recurrence. During the last years, genetic studies have allowed a better comprehension of pathological molecular mechanisms. The results will offer the rationale to develop new specific treatments for HUS.
Mele
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Istituto di Ricerche Farmacologiche Mario Negri, Centro di Ricerche Cliniche per le Malattie Rare, Aldo e Cele Daccò, Villa Camozzi, Ranica - Italy. mele@marionegri.it
Noris
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D017242:Complement Factor H; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D022603:Shiga Toxins
D022603:Shiga Toxins; D017242:Complement Factor H