HUS is classified into three main types based on etiology:
- Typical HUS (Shiga toxin-associated HUS): Caused by Shiga toxin-producing bacteria, especially E. coli O157:H7.
- Atypical HUS (aHUS): Related to genetic or acquired abnormalities in the alternative complement pathway.
- Secondary HUS: Associated with infections (non-Shiga toxin), medications, autoimmune disorders, or malignancies.
Etiopathogenesis
- Typical HUS:
- Shiga toxin binds to Gb3 receptors on endothelial cells, leading to cell injury.
- Endothelial damage triggers platelet aggregation and activation of the clotting cascade.
- Microvascular thrombosis causes hemolysis, thrombocytopenia, and renal damage.
- Atypical HUS:
- Genetic mutations lead to dysregulated complement activation, causing persistent endothelial injury.
- Common mutations involve CFH, CFI, and MCP genes.
- Secondary HUS:
- Triggered by systemic diseases or infections, leading to microangiopathic hemolysis and thrombosis.
Clinical Features
Key clinical triad:
- Microangiopathic Hemolytic Anemia (MAHA):
- Schistocytes on peripheral smear.
- Elevated LDH and indirect bilirubin; low haptoglobin.
- Thrombocytopenia:
- Platelet consumption due to microthrombi.
- Acute Kidney Injury (AKI):
- Oliguria, anuria, hypertension, and hematuria.
- Elevated creatinine and urea levels.
Other features:
- Gastrointestinal symptoms: Diarrhea (bloody in Shiga toxin HUS).
- Neurological symptoms: Seizures, encephalopathy (more common in aHUS).
Management
- Supportive Care:
- Volume management: Avoid fluid overload; manage dehydration in diarrhea-associated HUS.
- Electrolyte correction: Treat hyperkalemia and acidosis.
- Dialysis: Indicated for severe AKI.
- Transfusions: Red cell transfusions for anemia; avoid platelet transfusions unless significant bleeding.
- Specific Therapy:
- Shiga toxin HUS: Antibiotics not routinely recommended as they may worsen toxin release.
- Atypical HUS: Eculizumab (monoclonal antibody targeting complement C5).
- Plasma exchange/infusion in secondary HUS or aHUS with complement dysregulation.
- Monitoring and Prognosis:
- Monitor renal function, blood pressure, and hemolysis markers.
- Long-term follow-up for chronic kidney disease.
Key Highlights :
- Typical HUS is preceded by bloody diarrhea in 90% of cases.
- Gb3 receptor expression in renal endothelial cells explains kidney predilection in Shiga toxin HUS.
- Eculizumab has revolutionized the management of aHUS.
- Avoid NSAIDs and nephrotoxic drugs during acute phases.
- Mortality is higher in aHUS compared to typical HUS.
