What is the treatment for Atypical Hemolytic Uremic Syndrome (aHUS)?

Treatment of Atypical Hemolytic Uremic Syndrome (aHUS)

Eculizumab is the first-line treatment for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. 1

Understanding aHUS

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) characterized by:

• Microangiopathic hemolytic anemia
• Thrombocytopenia
• Acute kidney injury
• Uncontrolled activation of the alternative complement pathway

Unlike typical HUS, which is associated with Shiga toxin-producing E. coli (STEC), aHUS is primarily caused by genetic or acquired dysregulation of the complement system 2.

Diagnostic Approach

Before initiating treatment, it's crucial to establish the diagnosis of aHUS by:

1. Laboratory testing:

   • Complete blood count showing hemolytic anemia and thrombocytopenia
   • Evidence of microangiopathic hemolysis (schistocytes on peripheral smear)
   • Elevated LDH, low haptoglobin
   • Renal function tests showing acute kidney injury
   • Normal coagulation studies (to differentiate from DIC)

2. Specific diagnostic tests:

   • ADAMTS13 activity >10% (to rule out TTP)
   • Negative stool cultures for STEC (to rule out typical HUS)
   • Complement testing (C3, C4, genetic testing for complement mutations)
   • Rule out secondary causes (autoimmune diseases, drugs, malignancy)

Treatment Algorithm

First-Line Treatment

1. Eculizumab (Soliris):

   • Adult dosing: 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 1
   • Pediatric dosing: Weight-based according to FDA label 1

2. Pre-treatment requirements:

   • Meningococcal vaccination: Complete vaccination against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks prior to first dose 1
   • If urgent therapy is needed before vaccination is complete, provide antibiotic prophylaxis and administer vaccines as soon as possible 1

3. Monitoring during treatment:

   • Hematological parameters (platelets, LDH)
   • Renal function
   • Signs of meningococcal infection

Supportive Care

1. Management of acute kidney injury:

   • Fluid and electrolyte management
   • Renal replacement therapy if needed

2. Blood product support:

   • Red blood cell transfusions for symptomatic anemia
   • Platelet transfusions only if active bleeding or invasive procedures planned

3. Blood pressure control:

   • Aggressive management of hypertension

Special Considerations

Plasma Exchange/Plasma Infusion

• While historically used for aHUS, plasma therapy has been largely replaced by eculizumab
• If eculizumab is used with plasma exchange or plasma infusion, supplemental dosing is required 1

Kidney Transplantation

• For patients who progress to end-stage kidney disease, kidney transplantation with prophylactic eculizumab can prevent recurrence in the allograft 3
• Genetic testing should be performed before transplantation to assess risk of recurrence 4

Duration of Treatment

• Long-term treatment is typically required as aHUS is a chronic condition
• Some patients may be candidates for discontinuation of eculizumab under careful monitoring, particularly those without identified complement mutations 3

Monitoring and Follow-up

1. Regular monitoring:

   • Complete blood count
   • Renal function tests
   • Urinalysis
   • Blood pressure

2. Long-term follow-up:

   • Monitor for chronic kidney disease progression
   • Surveillance for potential meningococcal infections
   • Antibiotic prophylaxis until 2 weeks after vaccination 2

Common Pitfalls to Avoid

1. Delayed diagnosis and treatment initiation - early recognition and prompt treatment are critical for better outcomes
2. Inadequate meningococcal vaccination - patients on eculizumab are at increased risk for meningococcal infections
3. Misdiagnosis of other TMAs - careful differentiation from TTP, STEC-HUS, and secondary causes of TMA is essential
4. Inadequate monitoring - regular follow-up is needed to assess treatment response and detect complications early

Eculizumab has dramatically improved outcomes in aHUS, transforming a disease with historically poor prognosis (high mortality and progression to ESRD) to one with significantly better outcomes when treated promptly and appropriately 2, 5.