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BACKGROUND

Hemolytic uremic syndrome (HUS) was first described in 1955. It is one of the most frequent causes of acute renal failure in children and is defined by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The incidence of HUS is 2.7 cases per million people per year in the United States.1 HUS can occur at any age but most often presents between 2 months and 8 years of age, with equal male and female predominance. It has a seasonal peak in the summer and early fall.2 HUS is divided into two main categories, typical diarrhea-associated (D+ HUS) and atypical non-diarrhea associated HUS (aHUS). The most common form is D+ HUS, which is caused by Shiga toxin–producing bacteria and accounts for 90% of cases. Atypical HUS (aHUS), sometimes called D-HUS, accounts for the remaining cases (Table 113-1). Recently, it has become recognized that the two categories of HUS are not mutually exclusive. Some cases of HUS are multifactorial, with as many as 25% of patients with D+ HUS having mutations in complement system gene sequences.3

TABLE 113-1*Causes of Atypical Hemolytic Uremic Syndrome (aHUS)

PATHOPHYSIOLOGY

Typical D+ HUS

Shiga toxin-producing Escherichia coli (0157:H7 and other strains) are found in the gastrointestinal (GI) tract of beef cattle and can be isolated from inadequately cooked ground beef. Shiga toxin can also be produced by Shigella dysenteriae and may be present in contaminated water. Other reported vehicles of transmission include deer jerky, salami, unpasteurized milk, unpasteurized apple cider, salmon, and lettuce or radish sprouts.4 After an exposure to contaminated water or food, the average incubation period is 3 days prior to the development of diarrhea. Shiga toxin targets microvascular endothelial cells. This damaging effect on the vascular endothelium triggers multiple cellular and vascular phenomena leading to thrombus formation (a.k.a. thrombotic microangiopathy). Of note, urinary tract infections caused by Shiga toxin producing E. coli have also been reported prior to the development of HUS.5

Atypical HUS

In contrast to typical D+ HUS, aHUS can be seen in individuals with a genetic predisposition to complement dysregulation. Genetic mutations decrease the activity of complement regulatory proteins, and thus these individuals may have an uncontrolled complement response leading to endothelial damage and thrombosis when they are exposed to an inciting trigger. Environmental triggers such as infection, drugs such as immunosuppressants and oral contraceptives, and pregnancy can all trigger ...

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