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

Treatment of Atypical Hemolytic Uremic Syndrome (aHUS)

Eculizumab (a complement C5 inhibitor) is the first-line treatment for atypical HUS to inhibit complement-mediated thrombotic microangiopathy and prevent mortality and progression to end-stage kidney disease. 1

Immediate Management Approach

First-Line Therapy: Eculizumab

Initiate eculizumab immediately upon diagnosis of aHUS without waiting for genetic testing results, as complement-mediated TMA requires urgent treatment to prevent irreversible organ damage. 2, 1

Dosing for Adults (≥18 years):

• Induction: 900 mg IV weekly for 4 weeks
• Fifth dose: 1200 mg at week 5 (one week after fourth dose)
• Maintenance: 1200 mg every 2 weeks thereafter 1

Dosing for Pediatric Patients (<18 years):

Weight-based dosing is required 1:

• ≥40 kg: Adult dosing regimen
• 30-40 kg: 600 mg weekly × 2 doses, then 900 mg at week 3, then 900 mg every 2 weeks
• 20-30 kg: 600 mg weekly × 2 doses, then 600 mg at week 3, then 600 mg every 2 weeks
• 10-20 kg: 600 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 2 weeks
• 5-10 kg: 300 mg weekly × 1 dose, then 300 mg at week 2, then 300 mg every 3 weeks

Critical Pre-Treatment Requirements

Complete meningococcal vaccination (serogroups A, C, W, Y, and B) at least 2 weeks before initiating eculizumab, unless the risk of delaying therapy outweighs infection risk. 1

• If urgent therapy is required before vaccination completion, administer antibacterial prophylaxis (typically ciprofloxacin) and vaccinate as soon as possible 1
• Patients remain at increased risk for invasive meningococcal disease even after vaccination 1
• Monitor continuously for early signs of meningococcal infection (fever, headache, neck stiffness) and evaluate immediately if suspected 1

Alternative and Adjunctive Therapies

Plasma Exchange (When Eculizumab Unavailable)

Plasma exchange remains the primary alternative when eculizumab access is limited or for anti-Factor H antibody-associated aHUS. 2, 3

• Initiate daily plasma exchange at 1-1.5 plasma volumes (typically 60-80 mL/kg) using fresh frozen plasma as replacement fluid 3, 4
• Continue daily exchanges until hematological remission (platelet count >150 × 10⁹/L, normalized LDH, rising hemoglobin) 3, 5
• Median 6 sessions (range 5-8) typically required for hematological remission 3
• Plasma exchange is superior to plasma infusion alone due to lower risk of fluid overload and more effective antibody/complement removal 5, 4

Plasma Infusion Considerations:

• High-dose plasma infusion (25-30 mL/kg/day) may be used only when plasma exchange is unavailable 5
• Major limitation: Fluid overload occurs in approximately 30-40% of patients, often necessitating switch to plasma exchange 5
• Less effective for removing pathogenic antibodies or mutant complement proteins 5

Anti-Factor H Antibody-Positive aHUS

For patients with anti-Factor H autoantibodies, combine plasma exchange with immunosuppression to eliminate antibody production. 2, 6

• Continue intensive daily plasma exchange initially 6, 4
• Add immunosuppressive therapy (typically corticosteroids plus rituximab or cyclophosphamide) 6
• Monitor anti-Factor H antibody titers to guide treatment duration 6
• Transition to prophylactic plasma exchange (weekly to biweekly) after acute phase 4

Post-Transplant Management

Prophylactic eculizumab is essential for kidney transplant recipients with aHUS to prevent disease recurrence in the allograft. 2

• Initiate eculizumab before transplantation when possible 4
• Continue indefinitely post-transplant, as recurrence risk remains high (up to 60% without prophylaxis) 2
• If using plasma exchange instead, maintain at least weekly prophylactic exchanges post-transplant with immediate intensification if recurrence signs appear 4

Duration of Therapy

Continue eculizumab indefinitely for most patients with aHUS, as discontinuation carries high risk of relapse with potential for irreversible organ damage. 1, 7

• Complement dysregulation persists lifelong in genetic forms 7
• Even patients without identified mutations remain at risk for relapse 2
• Consider lifelong therapy unless specific low-risk genetic variants are identified 7

Supportive Care

Provide aggressive supportive management alongside specific complement-directed therapy:

• Maintain adequate hydration and electrolyte balance 7
• Initiate dialysis for severe acute kidney injury as needed 3, 7
• Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy 7
• Red blood cell transfusions are safe when indicated for severe anemia 7
• Control hypertension aggressively 7

Common Pitfalls to Avoid

Do not delay eculizumab while awaiting genetic testing results - complement studies take weeks to months, and irreversible organ damage occurs rapidly 2

Do not confuse aHUS with STEC-HUS - eculizumab is not indicated for Shiga toxin E. coli-related HUS, which is managed supportively 1, 7

Do not discontinue eculizumab prematurely - even after apparent remission, the underlying complement dysregulation persists 1, 7

Do not use direct oral anticoagulants if antiphospholipid antibodies are present - warfarin is superior for preventing thrombotic events in this context 2