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

Treatment of Atypical Hemolytic Uremic Syndrome (aHUS)

Complement inhibitors (eculizumab or ravulizumab) are the standard of care for atypical hemolytic uremic syndrome and should be initiated immediately as a medical emergency. 1, 2, 3

Immediate Management Priorities

Initiate Complement Inhibitor Therapy Without Delay

• Do not wait for genetic testing results before starting eculizumab or ravulizumab, as genetic mutations are found in only 50-60% of aHUS cases, and delaying therapy risks irreversible organ damage. 1

• Treatment should begin urgently with supportive measures while initiating complement inhibitor therapy, as aHUS is a medical emergency. 1

Concurrent Diagnostic Workup (Do Not Delay Treatment)

• Obtain ADAMTS13 activity level to exclude thrombotic thrombocytopenic purpura (TTP), as this requires different management. 1

• Perform stool testing for Shiga toxin/E. coli O157 to exclude STEC-HUS, which is not an indication for complement inhibitors. 1, 2, 3

• Check complement testing (C3, C4, CH50) and complement inhibitory antibodies. 1

• Confirm peripheral blood smear demonstrates schistocytes >1%, though absence should not exclude early diagnosis due to low sensitivity. 1

Specific Complement Inhibitor Dosing

Eculizumab (Soliris) for Adults

• Loading phase: 900 mg IV weekly for 4 weeks. 3

• Maintenance: 1200 mg IV at week 5, then 1200 mg every 2 weeks thereafter. 3

Ravulizumab (Ultomiris) for Adults ≥40 kg

• Loading dose: Weight-based (2400-3000 mg for 40-100 kg; 3000 mg for ≥100 kg). 2

• Maintenance: Weight-based (3000-3600 mg) every 8 weeks, starting 2 weeks after loading dose. 2

Mandatory Meningococcal Prophylaxis

• Vaccinate against meningococcal serogroups A, C, W, Y, and B at least 2 weeks before starting therapy whenever possible. 1, 2, 3

• If urgent therapy cannot be delayed for vaccination, provide immediate antibacterial prophylaxis and administer vaccines as soon as possible. 1, 2, 3

• Patients remain at increased risk for meningococcal infection even after vaccination and require long-term antimicrobial prophylaxis. 1

• Monitor patients continuously for early signs of meningococcal infection and evaluate immediately if suspected. 2, 3

Supportive Care During Initial Treatment

• Administer red blood cell transfusions according to existing guidelines for symptomatic anemia (typically targeting hemoglobin 7-8 g/dL in stable patients). 1, 4

• Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy. 1, 4

• Provide renal replacement therapy as needed for acute kidney injury. 1

Monitoring Treatment Response

• Assess platelet count normalization (target >150,000/mm³) every 2-4 weeks until doses stabilized. 1

• Monitor resolution of hemolysis: LDH normalization and disappearance of schistocytes on peripheral smear. 1, 4

• Track stabilization or improvement in renal function through serial creatinine measurements. 1

• In maintenance therapy, complement activity measurement (CCP activity targeted to <30%) can serve as a proxy for circulating drug levels and guide dosing intervals. 5

Critical Pitfalls to Avoid

• Never discontinue complement inhibitor therapy prematurely, as this carries a 10-20% risk of relapse with potential progression to renal failure. 1

• Do not delay eculizumab/ravulizumab while awaiting genetic confirmation, as treatment must begin based on clinical diagnosis. 1

• Recognize that patients requiring plasmapheresis, plasma exchange, or IVIg need supplemental dosing of complement inhibitors, as these procedures reduce drug levels. 2, 3

Special Clinical Contexts

• For pregnancy-triggered aHUS, C5 inhibitors should be initiated immediately and have been instrumental in resolving thrombotic microangiopathy. 1

• Patients being evaluated for kidney transplantation must continue complement inhibitor therapy to prevent recurrence of aHUS in the transplanted kidney. 1

• Patients of Chinese or Japanese descent may not respond to C5 inhibitors due to polymorphic variants of the C5 gene and require alternative management strategies. 1

Long-Term Management Considerations

• Monitor patients continuously for signs of relapse, including clinical presentation, laboratory abnormalities, and appearance of glomerular proteinuria. 1

• Renal transplantation may trigger aHUS recurrence or de novo disease in the renal graft, requiring continued complement inhibition. 1

• Offer genetic counseling to patients with confirmed aHUS diagnosis due to possible genetic transmission. 1

• A multidisciplinary team including hematology, nephrology, and transfusion medicine specialists is essential for optimal management. 1