What is Hemolytic Uremic Syndrome (HUS)?

From the Guidelines

Hemolytic uremic syndrome (HUS) is a serious condition characterized by the acute onset of microangiopathic hemolytic anemia, renal injury, and low platelet count, primarily caused by an infection with Shiga toxin-producing Escherichia coli (STEC). The most common form, called typical HUS, often occurs after an acute gastrointestinal illness, usually diarrhea 1. The toxin damages blood vessel walls, particularly in the kidneys, leading to blood clot formation, red blood cell destruction, and kidney failure.

Key Features of HUS

• Hemolytic anemia (destruction of red blood cells)
• Acute kidney injury
• Thrombocytopenia (low platelet count)
• Often caused by Shiga toxin-producing Escherichia coli (STEC) infection, particularly in children 1
• Can be preceded by bloody diarrhea, abdominal tenderness, and absence of fever 1

Diagnosis and Management

• Early identification of STEC infections is crucial to reduce the risk of complications and person-to-person transmission 1
• Detection of Shiga toxin or the genes that encode this toxin family is important for diagnosis 1
• Frequent monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine is recommended to detect hematologic and renal function abnormalities 1
• Treatment mainly involves supportive care, including careful fluid and electrolyte management, blood pressure control, and sometimes dialysis for kidney failure 1
• In severe cases, plasma exchange or the medication eculizumab (Soliris) may be used, particularly for atypical HUS which is caused by genetic factors rather than infection 1

Prevention

• Prevention focuses on proper food handling, thorough cooking of meat, and good hygiene practices to avoid E. coli infection 1
• Early identification and management of STEC infections can reduce the risk of complications and person-to-person transmission 1

From the Research

Definition of Hemolytic Uremic Syndrome (HUS)

• Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury 2.
• HUS is a type of thrombotic microangiopathy syndrome (TMA) defined as a triad of non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury 3.
• HUS is a thrombotic microangiopathy (TMA) defined by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury 4.

Classification of HUS

• HUS represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management, and outcome 2.
• HUS is classified into infectious, secondary, and atypical disease 4.
• Atypical hemolytic-uremic syndrome (aHUS) is associated with genetic mutations in complement and complement regulatory proteins 4.

Causes of HUS

• The most common etiology is infectious sequelae of Shiga toxin-producing Escherichia coli (STEC) 4.
• Other causative organisms include shigella and salmonella 4.
• Secondary HUS arises from cancer, chemotherapy, solid organ and hematopoietic stem cell transplant, pregnancy, or autoimmune disorders 4.

Clinical Manifestations of HUS

• HUS is characterized by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels 5.
• Atypical forms of HUS may present with arterial hypertension, proteinuria, and a progressive increase in serum creatinine 5.
• Nephrotic syndrome at disease onset is exceptional, but may occur in some cases of aHUS 5.

Diagnosis and Treatment of HUS

• Diagnosis of HUS is based on the presence of hemolytic anemia, thrombocytopenia, and acute kidney injury 2, 3, 4.
• Treatment of typical or Stx-HUS is mainly supportive, but it is critical to rule out other causes of TMAs, especially thrombotic thrombocytopenic purpura (TTP) 3.
• Eculizumab, a monoclonal antibody that inhibits the activation of C5, is used to treat atypical HUS (aHUS) 4, 6, 5.