Hemolytic uremic syndrome

Learning objectives

Hemolytic uremic syndrome (HUS) is a triad of renal failure, hemolytic anemia, and thrombocytopenia and is the most common cause of renal failure in infancy and childhood
HUS can lead to widespread inflammation and thrombotic microangiopathy, the formation of platelet microthrombi in the walls of small blood vessels
Most cases occur after infectious diarrhea due to a specific type of E. coli
Other causes include S. pneumonia, Shigella, Salmonella, and certain medications
Two predominant types:
- Typical HUS
  - Preceded by 4-6 days of diarrhea
  - Most commonly caused by infection with Shiga toxin-producing E. coli (O157:H7)
  - The mortality rate is 3%-5%
  - Approximately two-thirds of children require dialysis although 85% regain normal renal function
- Atypical HUS
  - 60-50% can be attributed to dysregulation of the alternative complement pathway
  - Involves mutations in factor H, factor I, CD46/MCP, factor B, and C3 components
  - A mortality rate of up to 25% in the acute phase
  - 50% of patients require renal replacement therapy at some point
The first symptoms of infection can emerge between 1 to 10 days later, but usually after 3 to 4 days
Affects about 1.5 per 100,000 people each year
A multisystemic disease affecting:

Cardiovascular system	Myocarditis Congestive heart failure Severe Hypertension
Respiratory system	Severe respiratory insufficiency Pulmonary edema Congestive heart failure
CNS	Drowsiness Seizures Hemiparesis Coma
Biochemical	Evidence of Acute kidney injury (AKI) Acid-base and electrolyte disturbances Abnormal liver function tests associated with hepatitis
Hematological	Hemolysis rapidly appears Hemoglobin falls to as low as 4 g/L Thrombocytopenia Hepatosplenomegaly
Renal system	Proteinuria, hematuria and oliguria leading to anuria
Gastrointestinal tract	Hemorrhagic gastritis
Immunological	Severe infections: peritonitis, meningitis, osteomyelitis

Abdominal pain, cramping, or bloating
Bloody diarrhea
Fever
Vomiting
Pale coloring, including loss of pink color in cheeks and inside the lower eyelids
Extreme fatigue
Shortness of breath
Easy bruising or unexplained bruises
Unusual bleeding
Decreased urination or blood in the urine
Edema
Confusion, seizures, or stroke
High blood pressure
Low platelets

Travel and dietary history
Complete blood count: anemia (Hb < 10 g/dl) and thrombocytopenia
Comprehensive metabolic panel (elevated creatinine, elevated indirect bilirubin, and elevated lactate dehydrogenase)
Urinalysis
Peripheral smear