Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome is a topic covered in the Select 5-Minute Pediatrics Topics.

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Basics

Description

  • 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.
  • HUS is one of the leading causes of acute kidney injury in infants and young children.
  • ∼90% of childhood cases are associated with Shiga toxin, primarily Shiga toxin–producing Escherichia coli (STEC-HUS, or typical HUS), and follow a diarrheal prodrome. Shigella dysenteriae is also a well-recognized infectious cause.
  • The term “atypical HUS” is used for non-STEC HUS and primarily refers to familial, complement-mediated HUS but encompasses a variety of sporadic causes of HUS including malignancies, Streptococcus pneumoniae infection, organ transplantation, pregnancy, collagen vascular disorder, or drugs such as calcineurin inhibitors and antiplatelet agents.
  • Atypical forms of HUS have a worse outcome than STEC-HUS.

Epidemiology

  • 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
  • Atypical HUS
    • 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 the Stx.
  • Atypical HUS 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.
  • Atypical HUS: 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.
  • One of the common causes of sporadic non–STEC-HUS is Streptococcus pneumoniae infection.

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Basics

Description

  • 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.
  • HUS is one of the leading causes of acute kidney injury in infants and young children.
  • ∼90% of childhood cases are associated with Shiga toxin, primarily Shiga toxin–producing Escherichia coli (STEC-HUS, or typical HUS), and follow a diarrheal prodrome. Shigella dysenteriae is also a well-recognized infectious cause.
  • The term “atypical HUS” is used for non-STEC HUS and primarily refers to familial, complement-mediated HUS but encompasses a variety of sporadic causes of HUS including malignancies, Streptococcus pneumoniae infection, organ transplantation, pregnancy, collagen vascular disorder, or drugs such as calcineurin inhibitors and antiplatelet agents.
  • Atypical forms of HUS have a worse outcome than STEC-HUS.

Epidemiology

  • 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
  • Atypical HUS
    • 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 the Stx.
  • Atypical HUS 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.
  • Atypical HUS: 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.
  • One of the common causes of sporadic non–STEC-HUS is Streptococcus pneumoniae infection.

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