What is the treatment for atypical hemolytic uremic syndrome (aHUS)?

Treatment of Atypical Hemolytic Uremic Syndrome (aHUS)

Complement inhibitors, specifically eculizumab or ravulizumab, are the standard of care for aHUS and should be initiated immediately as a medical emergency to prevent irreversible organ damage and death. 1, 2

Immediate Treatment Protocol

Pre-Treatment Requirements (Do Not Delay Therapy)

• Meningococcal vaccination is mandatory against serogroups A, C, W, Y, and B at least 2 weeks before starting treatment when possible 1, 2
• If urgent therapy is required, administer antibacterial prophylaxis (penicillin) immediately and vaccinate as soon as possible—do not delay eculizumab for vaccination 1, 2
• Long-term antimicrobial prophylaxis with penicillin is required throughout treatment due to increased meningococcal infection risk 1, 3

Eculizumab Dosing Regimen

For adults (≥18 years): 2

• Induction phase: 900 mg IV weekly for 4 weeks
• Fifth dose: 1200 mg IV at week 5 (one week after fourth dose)
• Maintenance: 1200 mg IV every 2 weeks thereafter

For pediatric patients (<18 years): Weight-based dosing 2

• 40 kg and over: 900 mg weekly × 4 doses, then 1200 mg at week 5, then 1200 mg every 2 weeks
• 30 to <40 kg: 600 mg weekly × 2 doses, then 900 mg at week 3, then 900 mg every 2 weeks
• 20 to <30 kg: 600 mg weekly × 2 doses, then 600 mg at week 3, then 600 mg every 2 weeks
• 10 to <20 kg: 600 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 2 weeks
• 5 to <10 kg: 300 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 3 weeks

Concurrent Supportive Management

• Red blood cell transfusions should be given for symptomatic anemia according to standard transfusion guidelines 1
• Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy 1
• Dialysis support as needed for acute kidney injury 1
• Blood pressure management with antihypertensive medications as required 1

Essential Diagnostic Testing (Obtain Before Treatment, But Do Not Delay Therapy)

• ADAMTS13 activity level to exclude thrombotic thrombocytopenic purpura (TTP)—must be >10% in aHUS 1
• Stool testing for Shiga toxin/E. coli O157 to exclude STEC-HUS 1, 2
• Complete blood count with peripheral smear demonstrating schistocytes >1% (though absence does not exclude early TMA) 1
• Complement testing: C3, C4, CH50, and complement inhibitory antibodies 1
• Genetic testing for complement mutations (but do not delay treatment awaiting results—only 50-60% have identifiable mutations) 1

Monitoring Treatment Response

Assess response every 2-4 weeks initially: 1

• Platelet count normalization (target >150,000/mm³)
• Resolution of hemolysis: LDH normalization, disappearance of schistocytes
• Renal function: Stabilization or improvement in serum creatinine
• Complete blood count until doses are stabilized

Critical Treatment Considerations

• Treatment timing is critical: Delays in initiating eculizumab are associated with increased morbidity and mortality—treatment should begin within hours of diagnosis 3
• Do not discontinue therapy prematurely: Stopping complement inhibitors carries a 10-20% risk of disease relapse with potential renal failure 1
• Lifelong treatment is typically required, especially in patients with identified genetic mutations or those being evaluated for kidney transplantation 1
• Plasma exchange/plasmapheresis requires supplemental dosing of eculizumab to maintain therapeutic levels 2

Special Populations

• Pregnancy-triggered aHUS: C5 inhibitors should be initiated immediately and are effective in resolving TMA 1
• Transplant candidates: Maintenance therapy is essential to prevent aHUS recurrence in the transplanted kidney 1
• Patients of Chinese/Japanese descent: May not respond to C5 inhibitors due to polymorphic variants of the C5 gene—consider alternative complement inhibitors 1

REMS Program Requirement

• Eculizumab is only available through the ULTOMIRIS and SOLIRIS REMS program due to meningococcal infection risk 2
• Healthcare providers must enroll in the REMS program before prescribing 2

Common Pitfalls to Avoid

• Never delay eculizumab while awaiting genetic testing results—genetic mutations are found in only 50-60% of cases, and treatment must begin immediately 1
• Do not confuse aHUS with STEC-HUS—eculizumab is not indicated for Shiga toxin E. coli-related HUS 2
• Do not stop treatment without thorough risk assessment—discontinuation carries significant relapse risk 1
• Ensure meningococcal vaccination and prophylactic antibiotics are in place—life-threatening meningococcal infections can occur rapidly 1, 2