Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome (original) (raw)

2016, Kidney International

A typical hemolytic uremic syndrome (aHUS) is a progressive life-threatening thrombotic microangiopathy (TMA) associated with dysregulation of the complement alternative pathway. 1-3 Complement gene mutations (e.g., complement factor H [CFH], membrane cofactor protein [MCP], complement factor I [CFI], complement factor B [CFB], complement protein 3 [C3]), or factor H autoantibodies are identified in 50% to 60% of patients with aHUS. 4-6 Abnormalities in genes encoding thrombomodulin, plasminogen, and diacylglycerol kinase ε (DGKE) 7-9 occur in a small number of patients. Evidence of a genetic abnormality is not required for diagnosis. 4,10-13 Although onset may occur at any age, 40% of patients develop aHUS by 18 years of age. 1,2,5 Clinical manifestations in children generally include anemia, thrombocytopenia, and acute kidney injury, 5 but peripheral gangrene, 14 arterial stenoses, 15 dilated cardiomyopathy, cardiorespiratory arrest, 16 and neurologic, 5,17 pulmonary, 11 and gastrointestinal complications 17 have been reported. Historically, aHUS was managed with plasma exchange/plasma infusion (PE/PI) and was associated with high morbidity and mortality rates, 1-3,5,18 with children having higher mortality than adults. 5 PE/PI may induce stabilization of hematologic parameters (but generally not significant renal function improvement), 19 is associated with complications, and impairs quality of life. 19,20 The availability of eculizumab (Soliris, Alexion Pharmaceuticals, Inc., Cheshire, CT, USA) 21,22an anti-C5 monoclonal antibody and the first and only currently approved therapy for adult and pediatric patients-has profoundly changed aHUS management. 13,23 The efficacy and safety of