What is the diagnosis and treatment for Hemolytic Uremic Syndrome (HUS)?

From the Guidelines

Hemolytic Uremic Syndrome (HUS) should be diagnosed and treated with a focus on supportive care, including fluid and electrolyte management, blood transfusions, and dialysis, as well as avoiding antibiotics in cases of Shiga toxin-producing E. coli, as recommended by the 2017 Infectious Diseases Society of America clinical practice guidelines 1. The diagnosis of HUS involves monitoring of hemoglobin and platelet counts, electrolytes, and blood urea nitrogen and creatinine to detect hematologic and renal function abnormalities, as well as examining a peripheral blood smear for red blood cell fragmentation 1. Key aspects of treatment include:

• Fluid and electrolyte management: Intravenous fluids to maintain hydration and correct electrolyte imbalances
• Blood transfusions: Packed red blood cells for severe anemia; platelet transfusions if bleeding occurs
• Dialysis: Temporary renal replacement therapy may be necessary for acute kidney injury
• Avoiding antibiotics in cases of Shiga toxin-producing E. coli to prevent increased toxin release and worsening of HUS
• Blood pressure control: Use of antihypertensive medications as needed
• Nutritional support: Ensuring adequate nutrition, potentially through enteral or parenteral feeding It is essential to monitor patients closely for complications such as seizures, heart failure, or multiorgan dysfunction, and long-term follow-up is necessary as some patients may develop chronic kidney disease. The pathophysiology of HUS involves endothelial damage, leading to microthrombi formation in small blood vessels, particularly in the kidneys, resulting in hemolysis, platelet consumption, and renal impairment, which supports the use of supportive care and potential benefit of complement inhibition in atypical cases, as noted in the guidelines 1.

From the FDA Drug Label

SOLIRIS is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. Limitation of Use SOLIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). For patients 18 years of age and older, SOLIRIS therapy consists of: 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter

The diagnosis of Hemolytic Uremic Syndrome (HUS) is not directly stated in the drug label, but it can be inferred that atypical HUS (aHUS) is a condition where complement-mediated thrombotic microangiopathy occurs. The treatment for aHUS is eculizumab (SOLIRIS), which is administered intravenously, with a recommended dosage regimen of 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter 2.

• Key points:
  • Eculizumab is not indicated for the treatment of Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
  • The dosage regimen may vary depending on the patient's age and weight.
  • Patients receiving eculizumab are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination 2.

From the Research

Diagnosis of Hemolytic Uremic Syndrome (HUS)

• HUS is defined by the simultaneous occurrence of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure 3, 4
• The diagnosis of HUS is based on clinical signs and symptoms, including hemolytic anemia, thrombocytopenia, and acute renal failure 3, 4, 5, 6
• Laboratory tests, such as blood counts, renal function tests, and stool tests for Shiga toxin-producing Escherichia coli (STEC), can help confirm the diagnosis 3, 4, 6

Classification of HUS

• HUS can be classified into two primary types:
  • HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS) 3, 6
  • HUS related to complement, such as atypical HUS (aHUS) which is not diarrhea associated (D-HUS, aHUS) 3, 4, 5, 6
• Other forms of HUS can occur in the course of systemic diseases or physiopathological conditions, such as pregnancy, after transplantation, or after drug assumption 3, 5

Treatment of HUS

• Typical management of STEC-HUS patients relies on supportive care, including treatment of electrolyte and water imbalance, anemia, hypertension, and renal failure 3
• For atypical HUS, the initial management is supportive and similar to the approach for STEC-HUS, but may also include specific therapies, such as eculizumab, a monoclonal antibody that blocks the C5 cascade 3, 6, 7
• Plasma therapies, such as plasma infusions and plasma exchanges, can be effective in treating hemolysis and thrombocytopenia in some cases of HUS 5, 6, 7
• Renal transplantation may be considered in patients with end-stage renal disease (ESRD), but the risk of recurrence is higher in genetic forms of complement regulatory protein deficiency 3, 5