Atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS), also known as complement-mediated hemolytic uremic syndrome, is a rare and severe disease caused by chronic, uncontrolled activation of the complement system, a part of the immune system that normally helps fight infections. Unlike typical HUS, which is triggered by Shiga toxin-producing Escherichia coli (STEC) infection, aHUS results from genetic mutations or acquired autoantibodies that dysregulate the alternative complement pathway. The disease primarily affects the kidneys, blood, and vascular system, leading to a triad of microangiopathic hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and acute kidney injury. Thrombotic microangiopathy (TMA), the hallmark of the disease, involves damage to the small blood vessels, leading to blood clot formation in multiple organs. aHUS can present at any age, from the neonatal period through adulthood, and may be triggered by infections, pregnancy, surgery, or other complement-activating events. Mutations in genes encoding complement regulatory proteins — including CFH, CFI, MCP (CD46), CFB, C3, and THBD — have been identified in approximately 60% of patients. Additionally, about 5-10% of patients have autoantibodies against complement factor H. Symptoms include fatigue, pallor, decreased urine output, edema, hypertension, and in severe cases, neurological complications such as seizures or confusion. Without treatment, aHUS carries a high risk of end-stage kidney disease and mortality. The treatment landscape for aHUS has been transformed by the availability of complement inhibitors, particularly eculizumab and ravulizumab, which are monoclonal antibodies that block the terminal complement protein C5. These therapies have dramatically improved outcomes by preventing ongoing complement-mediated TMA. Plasma exchange or plasma infusion was historically used and may still serve as a bridging therapy. Supportive care includes management of hypertension, dialysis when needed, and careful monitoring of kidney function. Kidney transplantation is an option for patients who progress to end-stage renal disease, though recurrence risk depends on the underlying genetic defect. Genetic testing and family screening are recommended to guide treatment decisions and assess prognosis.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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