Atypical Hemolytic Uremic Syndrome

Atypical HUS results from dysregulation of the alternative complement pathway, often triggered by genetic mutations in complement pathway genes (CFH, MCP, CFI, C3, CFB, THBD) or autoantibodies against Factor H. Environmental triggers may include infections, medications, pregnancy, or malignancy. Unlike Shiga toxin-producing E. coli HUS, aHUS is not preceded by diarrheal illness. The uncontrolled complement activation generates C5a and C5b-9, causing endothelial damage in the kidney microvasculature, platelet consumption, and mechanical destruction of red blood cells (hemolytic anemia). This thrombotic microangiopathy characteristically affects the renal microcirculation, leading to progressive kidney injury. aHUS presents with the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, often progressing rapidly to end-stage renal disease if untreated. About 50% of untreated patients develop chronic kidney disease or end-stage renal disease. Extrarenal manifestations occur in 10-15% of patients, including thrombotic events, neurological complications, and cardiac involvement. Recurrence risk after kidney transplantation is high without complement-targeted prevention. Early recognition and prompt treatment with complement inhibitors such as eculizumab (C5 inhibitor) or other newer agents has dramatically improved outcomes.