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

Treatment of Hemolytic Uremic Syndrome (HUS)

The treatment of HUS depends critically on distinguishing between typical STEC-HUS (which requires supportive care only) and atypical HUS (which requires immediate complement inhibitor therapy with eculizumab or ravulizumab), as this distinction directly impacts mortality and long-term renal outcomes. 1, 2

Immediate Diagnostic Differentiation

Before initiating treatment, you must rapidly distinguish between HUS subtypes:

• Order ADAMTS13 activity, stool testing for Shiga toxin/VTEC, and complement testing (C3, C4, CH50) immediately upon suspicion of HUS 1, 2
• STEC-HUS is diagnosed by positive stool VTEC testing AND diarrhea onset 4-5 days before HUS symptoms 2
• Atypical HUS is diagnosed by negative VTEC testing OR short diarrhea period OR simultaneous onset of diarrhea and HUS 2
• Do not delay treatment while awaiting genetic testing results - aHUS is a medical emergency and genetic mutations are found in only 50-60% of cases 1

Treatment Algorithm by HUS Type

For Typical STEC-HUS (Post-Diarrheal)

Supportive care is the standard of care; complement inhibitors are NOT indicated and may cause harm. 3, 4

• Provide meticulous fluid and electrolyte management with careful monitoring of volume status 5, 6
• Initiate renal replacement therapy (dialysis) when indicated - approximately two-thirds of children with STEC-HUS will require dialysis 5
• Manage hypertension aggressively with antihypertensive therapy as needed 5
• Transfuse red blood cells for symptomatic anemia according to standard transfusion guidelines 1
• Avoid platelet transfusions unless life-threatening bleeding occurs - they may worsen thrombotic microangiopathy 1
• Do NOT use antidiarrheal medications - these are contraindicated in STEC-HUS 5
• Avoid antibiotics during acute STEC infection - there is evidence they may worsen outcomes 5
• Monitor daily: hemoglobin, platelet counts, electrolytes, BUN, and creatinine during days 1-14 7

For Atypical HUS (Complement-Mediated)

Initiate complement inhibitor therapy immediately as a medical emergency - eculizumab or ravulizumab are the standard of care and dramatically improve survival and renal outcomes. 1, 3

Pre-Treatment Requirements (Do NOT Delay Therapy)

• Vaccinate against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks before first dose if possible 3
• If urgent therapy is needed and patient is not vaccinated, provide antibacterial prophylaxis immediately and vaccinate as soon as possible 3
• Enroll in the ULTOMIRIS and SOLIRIS REMS program - eculizumab is only available through this restricted program 3

Eculizumab Dosing for aHUS

For adults (≥18 years and ≥40 kg): 3

• 900 mg IV weekly for 4 weeks
• Then 1200 mg IV at week 5
• Then 1200 mg IV every 2 weeks thereafter

For pediatric patients (weight-based dosing): 3

• 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

Concurrent Supportive Management for aHUS

• Provide red blood cell transfusions for symptomatic anemia using extended antigen-matched cells when feasible 1
• Avoid platelet transfusions unless life-threatening bleeding 1
• Initiate renal replacement therapy when indicated 5
• Manage hypertension aggressively 5
• Consider plasma exchange or fresh frozen plasma infusion in severe cases or while awaiting complement inhibitor availability - FFP contains factor H at physiological concentrations 5, 6

Monitoring Response to Complement Inhibitor Therapy

• Assess platelet count normalization (target >150,000/mm³) 1
• Monitor for resolution of hemolysis (LDH normalization, disappearance of schistocytes) 1
• Track stabilization or improvement in renal function (serum creatinine) 1
• Perform complete blood count every 2-4 weeks until doses stabilized 1

Critical Pitfalls to Avoid

• Never withhold eculizumab/ravulizumab while awaiting genetic testing - only 50-60% of aHUS cases have identifiable mutations 1
• Never discontinue complement inhibitor therapy prematurely - this carries a 10-20% risk of relapse with potential renal failure 1, 2
• Never use antibiotics in acute STEC infection - they may increase Shiga toxin release 5
• Never give antidiarrheal medications in suspected STEC-HUS 5
• Do not delay complement inhibitor therapy for meningococcal vaccination - provide antibiotic prophylaxis and vaccinate concurrently if urgent treatment needed 3

Special Clinical Contexts

Pregnancy-Triggered aHUS

• Initiate C5 inhibitors (eculizumab/ravulizumab) immediately - these have been instrumental in resolving TMA in pregnancy-associated aHUS 1

Transplant-Related aHUS

• Maintain complement inhibitor therapy in patients with aHUS undergoing kidney transplantation to prevent recurrence in the transplanted kidney 1
• Recognize that renal transplantation may trigger aHUS either as recurrent disease or de novo in the graft 1

Neurological Involvement

• If neurological symptoms present (occurs in 10-20% of aHUS cases), obtain neurology consultation, EEG, and brain MRI 2
• Continue aggressive complement inhibitor therapy - neurological manifestations do not change the treatment approach 2

Long-Term Management Considerations

• Patients with aHUS require indefinite complement inhibitor therapy - discontinuation carries significant relapse risk 1, 2
• Maintain meningococcal vaccination status and provide long-term antimicrobial prophylaxis for patients on complement inhibitors 1
• Monitor for signs of relapse including clinical presentation, laboratory data, and glomerular proteinuria 1
• Offer genetic counseling to patients with confirmed aHUS diagnosis due to possible genetic transmission 1
• Note that patients of Chinese and/or Japanese descent may not respond to C5 inhibitors due to polymorphic variants of the C5 gene 1