Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome is a topic covered in the 5-Minute Pediatric Consult.

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Basics

Description

  • Hemolytic uremic syndrome (HUS) is characterized by the triad of acute kidney injury, thrombocytopenia, and hemolytic anemia with fragmentation of erythrocytes (schistocytes noted on peripheral smear).
  • Kidney dysfunction may manifest as hematuria and/or proteinuria and/or azotemia.
  • The term “atypical HUS” (aHUS) is used for non-Shiga toxin–producing Escherichia coli (STEC) HUS and specifically refers to familial complement-mediated HUS (does not include the sporadic causes listed below).
  • aHUS generally has a worse outcome than STEC-HUS.

Epidemiology

  • HUS is one of the leading causes of acute kidney injury in infants and young children.
    • Approximately 90% of childhood cases are associated with STEC-HUS, or typical HUS, and follow a diarrheal prodrome. Shigella dysenteriae is also a well-recognized infectious cause.
    • Other sporadic causes of HUS include:
      • Malignancy
      • Bone marrow and solid organ transplantation drugs (such as calcineurin inhibitors and antiplatelet agents)
      • Malignant hypertension
      • Autoimmune disorders (such as SLE and antiphospholipid syndrome)
      • Certain infections (Streptococcus pneumoniae, influenza, HIV)
  • STEC-HUS
    • Tends to occur in the summer months and may be sporadic or occur in epidemic outbreaks
    • Occurs mainly in older infants and young children between 6 months and 5 years of age
  • aHUS
    • Has no seasonal variation and can occur at any age (including early infancy); may be sporadic or familial

General Prevention

  • STEC is primarily found in the intestine of ruminants, particularly cattle, and can be transmitted by undercooked beef, unpasteurized milk, or by contamination of water and produce.
  • For adequate prevention, practice good hand hygiene, wash food well, and cook food, especially meat, thoroughly.

Pathophysiology

  • Vascular endothelial cell injury is central to the pathogenesis of all forms of HUS.
  • STEC colonize colonic mucosa, adhere to mucosal villi, and release Shiga toxin (Stx).
  • Stx enters the systemic circulation, where it causes endothelial cell injury via inflammation, upregulation of chemokine and cytokine production, and by binding to endothelial cell surface receptors (Gb3) and interrupting protein synthesis.
  • Endothelial cell injury exposes the thrombogenic basement membrane, causing platelet activation and local intravascular thrombosis.
  • In vitro studies show that glomerular endothelial cells and proximal tubular epithelial cells have receptors with very high affinity for Stx.
  • aHUS is caused by dysregulation of the alternate complement pathway.

Etiology

  • STEC-HUS: Most cases are caused by the O157:H7 strain of E. coli.
    • STEC most commonly infects children from 6 months to 5 years of age in the summer and the fall. The primary reservoir is cattle.
    • A negative stool culture in a patient who has HUS does not rule out STEC.
    • 10–15% of children who contract STEC+ E. coli 0157:H7 gastroenteritis develop HUS.
  • aHUS: Mutations of complement regulatory proteins are identifiable in ~60% of cases, with either an autosomal dominant or recessive inheritance. Reported mutations include complement factor H (most frequent), I, and B; membrane cofactor protein; and C3. Autoantibodies to complement factor H have also been reported as a cause of aHUS.
  • One of the common causes of sporadic non-STEC-HUS is S. pneumoniae infection.

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