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

Treatment of Hemolytic Uremic Syndrome (HUS)

For atypical HUS (aHUS), initiate eculizumab 900 mg weekly for 4 weeks, then 1200 mg at week 5, followed by 1200 mg every 2 weeks thereafter, as this is the first-line therapy that produces rapid and sustained inhibition of complement-mediated thrombotic microangiopathy. 1, 2, 3, 4

Critical First Steps: Distinguish HUS Type

The treatment approach differs fundamentally based on HUS subtype, making accurate diagnosis essential before initiating therapy:

Immediate Diagnostic Workup

• ADAMTS13 activity level (to exclude TTP; should be >10% in HUS) 1
• Stool testing for Shiga toxin/E. coli O157:H7 (to distinguish STEC-HUS from aHUS) 1
• Complement testing (C3, C4, CH50) if aHUS suspected 1
• Peripheral blood smear for schistocytes (essential for TMA diagnosis) 1
• CBC, LDH, haptoglobin, indirect bilirubin, reticulocyte count to confirm hemolysis 1, 2
• Serum creatinine and urinalysis to assess renal involvement 1
• Direct antiglobulin test (Coombs) to exclude immune-mediated hemolysis 1, 2

Common pitfall: Do not wait for genetic testing results before initiating treatment for suspected aHUS, as this is a clinical diagnosis and delays increase mortality 1, 5

Treatment by HUS Subtype

Atypical HUS (Complement-Mediated)

Eculizumab is first-line therapy and should be initiated immediately upon diagnosis 1, 2, 3, 4:

Dosing for Adults (≥40 kg):

• Induction: 900 mg IV weekly × 4 doses 1, 3
• Week 5: 1200 mg IV 3
• Maintenance: 1200 mg IV every 2 weeks indefinitely 1, 3

Mandatory Pre-Treatment Requirements:

• Meningococcal vaccination (serogroups A, C, W, Y, and B) at least 2 weeks before first dose if possible 1, 3
• If urgent therapy needed: Administer antibacterial prophylaxis (ciprofloxacin) and vaccinate as soon as possible 1, 3
• Enrollment in REMS program required 3

Alternative/Historical Therapy (Now Second-Line):

• Plasma exchange (PE) was previously used but is mostly ineffective at preventing organ damage compared to eculizumab 4, 6
• Consider PE only if eculizumab unavailable or while awaiting definitive diagnosis 4, 7

Evidence strength: Eculizumab produces significant improvements in long-term clinical outcomes and is approved as first-line therapy based on its rapid and sustained inhibition of the TMA process 4, 6

STEC-HUS (Shiga Toxin-Associated)

Management is primarily supportive, as the disease course is typically self-limiting 4, 6, 7:

• Supportive care with fluid management to maintain renal perfusion 7, 8
• Dialysis if severe acute kidney injury develops 6, 8
• RBC transfusion if hemoglobin <7-8 g/dL or symptomatic anemia 2
• Platelet transfusion generally avoided unless life-threatening bleeding 1

Critical Avoidances:

• Do NOT use antibiotics during acute phase (may increase Shiga toxin release) 7
• Avoid antimotility agents, narcotics, and NSAIDs 7

Note: Eculizumab is NOT indicated for STEC-HUS 3

Grading and Management Algorithm

Grade 1-2 (Evidence of hemolysis without severe clinical consequences):

• Continue monitoring with close laboratory follow-up 1
• Supportive care including hydration 1
• Hold causative agents if drug-induced 1, 9

Grade 3 (Laboratory findings with clinical consequences):

• Permanently discontinue immune checkpoint inhibitors if drug-induced 1
• Begin eculizumab therapy for aHUS as outlined above 1
• Hematology consultation 1

Grade 4 (Life-threatening consequences: CNS thrombosis, renal failure):

• Immediate eculizumab initiation for aHUS 1
• Methylprednisolone 1 g IV daily × 3 days may be considered in conjunction with hematology 1
• RBC transfusion for severe anemia 1, 2
• Intensive monitoring in ICU setting 1

Supportive Care (All HUS Types)

• Folic acid 1 mg daily to support erythropoiesis 2
• RBC transfusion targeting hemoglobin 7-8 g/dL in stable patients 1, 2
• Renal replacement therapy as needed for acute kidney injury 6, 8
• Blood pressure management for hypertension 1
• Monitor for neurologic complications (seizures, altered mental status) with EEG and brain MRI if suspected 1

Long-Term Considerations

• Genetic testing should be performed to identify complement pathway mutations (CFH, CFI, CD46, C3, CFB, THBD, DGKE) 1
• Family screening recommended if genetic mutation identified 1
• Indefinite eculizumab therapy typically required for aHUS to prevent relapse 3, 4
• Monitor for long-term renal sequelae as nephron loss is common even with treatment 8
• Pre-transplant planning: aHUS frequently recurs after renal transplantation; prophylactic eculizumab recommended 6, 8

Critical distinction: The 2025 Italian consensus emphasizes that absence of marked thrombocytopenia or significant anemia should not exclude TMA diagnosis, particularly in post-transplant patients 1