Hemolytic Uremic Syndrome (HUS)

Overview

Hemolytic uremic syndrome (HUS) is an acute condition characterized by intravascular hemolytic anemia and renal failure of unknown origin. A multisystem disorder, it primarily features microangiopathic hemolysis, acute kidney injury, and thrombocytopenia, making it one of the most common causes of pediatric acute renal failure. Over one-third of affected children exhibit neurological involvement. Given the overlapping etiology, pathogenesis, and clinical manifestations with thrombotic thrombocytopenic purpura (TTP), many experts now classify HUS and TTP as spectrum disorders under the umbrella term HUS/TTP or thrombotic microangiopathy (TMA). Advances in diagnosis and treatment have significantly improved outcomes.

Etiology

1. Primary HUS: Idiopathic, often linked to genetic predisposition (autosomal recessive/dominant inheritance), with familial cases reported.
2. Secondary HUS:
   • Infections:
     • E. coli O157:H7 (produces Shiga toxin) and Shigella dysenteriae type 1 are major culprits.
     • Streptococcus pneumoniae (via neuraminidase), Salmonella, Campylobacter, and viruses (e.g., Coxsackie, influenza, EBV) may also trigger endothelial injury.
   • Immunodeficiency: Seen in agammaglobulinemia or thymic dysplasia.
   • Drugs: Cyclosporine, mitomycin, oral contraceptives.
   • Other: Pregnancy, organ transplants, glomerular diseases, malignancies.
3. Recurrent HUS: Associated with genetic traits or post-transplant cases.

Clinical Presentation

• Prodrome:
  • 80–90% present with gastroenteritis (abdominal pain, vomiting, bloody diarrhea).
  • 10–15% have respiratory infections.
  • Absence of prodromal symptoms correlates with higher mortality.
• Acute Phase:
  • Rapid onset of hemolytic anemia, oliguria/anuria, and bleeding tendencies.
  • Key signs: pallor, hypertension (30–60%), hepatosplenomegaly (30–50%), jaundice (15–30%), petechiae.
• Renal Involvement:
  • 86–100% develop oliguria; 30% progress to anuria.
  • Chronic kidney disease or hypertension may persist post-recovery.

Diagnostic Workup

1. Blood Tests:
   • Severe anemia (Hb 30–50 g/L), elevated reticulocytes, hyperbilirubinemia.
   • Schistocytes (fragmented RBCs) on peripheral smear.
   • Thrombocytopenia (platelets ~75×10⁹/L) in 90% of cases.
2. Coagulation Studies:
   • Early: Prolonged PT, hypofibrinogenemia, elevated FDPs.
3. Urinalysis:
   • Hematuria, proteinuria, hemoglobinuria (in severe hemolysis).
4. Renal Function: Metabolic acidosis, hyperkalemia, azotemia.

Diagnosis

Based on the triad of hemolysis, thrombocytopenia, and acute kidney injury. Differential diagnoses include other causes of renal failure, glomerulonephritis, and hemolytic anemias.

Complications

• Acute: Pulmonary edema, hypertensive crisis, hyperkalemia.
• Chronic: CKD, neurological sequelae (cognitive impairment, epilepsy).

Treatment

No cure exists; management focuses on supportive care:

1. Acute Renal Failure:
   • Fluid/electrolyte balance, antihypertensives, dialysis (for anuria, refractory hyperkalemia, or fluid overload).
2. Anemia:
   • Packed RBC transfusions if Hb <50 g/L; platelet transfusions for bleeding.
3. Anticoagulation (controversial):
   • Heparin (early use, cautious monitoring).
   • Antiplatelets (low-dose aspirin, high-dose dipyridamole).
   • PGI₂ infusion or plasma exchange (experimental).
4. Avoid: Corticosteroids (prothrombotic); plasma transfusion in S. pneumoniae-associated HUS.

Prognosis

• Mortality dropped from 40–50% (1950s) to 4.5–15% with modern therapies.
• Poor outcomes linked to CNS involvement, recurrence, or familial cases.