Atypical hemolytic uremic syndrome: pathophysiology, clinical presentation, and treatment strategies

Atypical hemolytic uremic syndrome (aHUS) is a rare and potentially life-threatening thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Without timely intervention, it may progress to end-stage kidney disease. The condition is primarily attributed to dysregulation of the alternative complement pathway, with up to 60% of patients exhibiting genetic mutations in complement regulatory proteins such as complement factor H, complement factor I, membrane cofactor protein, and thrombomodulin. The introduction of complement inhibitors, such as eculizumab and ravulizumab, has significantly improved clinical outcomes by reducing recurrence and preserving renal function. These advances have redefined treatment approaches, particularly in pediatric patients and those undergoing kidney transplantation. The prophylactic use of complement inhibitors is now recommended for transplant recipients with moderate to high genetic risk. This review aimed to examine the pathophysiology, clinical manifestations, and treatment strategies of aHUS. Early and targeted complement inhibition is essential for preventing irreversible kidney damage and optimizing outcomes, particularly in children and transplant recipients.