Hemolytic-Uremic Syndrome (HUS)

Key Features

Essentials of Diagnosis

• Bloody diarrhea is the usual presenting complaint, followed by hemolysis, thrombocytopenia, and renal failure

• Circulating toxin causes endothelial damage, which leads to platelet deposition/consumption, and microvascular occlusion with subsequent hemolysis

• Similar microvascular endothelial activation may also be triggered by

  • Drugs (eg, cyclosporine)

  • Viruses (HIV)

  • Pneumococcal infections

• Rare cases are caused by genetic factors causing complement dysregulation (eg, factor H deficiency)

General Considerations

• Most common glomerulovascular cause of acute renal failure in childhood

• Diarrhea-associated form

  • Usually the result of infection with Shiga toxin–producing strains of Shigella or Escherichia coli

  • Ingestion of undercooked ground beef or unpasteurized foods is a common source

• There are many serotypes, but the most common pathogen in the United States is E coli O157:H7

Clinical Findings

• HUS due to Shigella or E coli

  • Begins with a prodrome of abdominal pain, diarrhea, and vomiting

  • Oliguria, pallor, and bleeding manifestations (principally gastrointestinal) occur next

• Pneumococcal-associated HUS typically presents with

  • Documented pneumococcal pneumonia

  • Sepsis

  • Meningitis

• Atypical HUS associated with complement dysregulation

  • An episode of HUS often develops following intercurrent illness

  • Presents with malaise and pallor

• Hypertension and seizures develop in some children—especially those in whom severe renal failure and fluid overload develop

• There may also be significant endothelial involvement in the central nervous system (CNS), heart, and pancreas

Diagnosis

• Anemia may be profound

• Red blood cell (RBC) fragments are seen on blood smears

• Thrombocytopenia is often severe, but other coagulation abnormalities are less consistent

• Serum fibrin split products are often present, but fulminant disseminated intravascular coagulation is rare

• Hematuria and proteinuria are often present

• Hemoglobinuria is occasionally observed due to marked RBC hemolysis

Treatment

• Meticulous attention to fluid and electrolyte status is crucial

• Antimotility agents and antibiotics for HUS caused by gastrointestinal infection should be avoided because antibiotics may cause release of large amounts of Shiga toxin

• Timely dialysis improves the prognosis

• RBC transfusions are often necessary

• Platelet transfusions should be avoided unless there is active bleeding

• Erythropoietin (epoetin alfa)

  • May reduce RBC transfusion needs

  • Indicated for patients with renal failure

• Atypical HUS due to complement dysregulation

  • May benefit from plasmapheresis or plasma infusion

  • However, eculizumab has replaced these therapies

• Plasma therapy should be avoided in pneumococcal HUS because it drives the HUS process by providing the anti–Thomsen-Friedenreich antibody

Outcome

Follow-Up

• Includes serial determinations of renal function with frequency dictated by the etiology, course, and subsequent findings and routine monitoring of blood pressure

Complications

• Complications of acute kidney injury occur

• Neurologic problems, particularly seizures, may result from hyponatremia, hypertension, or CNS vascular disease

• Despite thrombocytopenia, many children are thrombophilic due to the underlying endothelial damage