Treatment of Atypical Hemolytic Uremic Syndrome (aHUS)
Complement inhibitors (eculizumab or ravulizumab) are the standard of care for aHUS and should be initiated immediately as a medical emergency, even before genetic testing results are available. 1, 2
Immediate Treatment Initiation
Start complement inhibitor therapy urgently without waiting for confirmatory genetic testing, as only 50-60% of aHUS cases have identifiable genetic mutations, and treatment delay significantly worsens outcomes. 1
Eculizumab dosing for adults (≥18 years) with aHUS: 900 mg IV weekly for 4 weeks, then 1200 mg at week 5, followed by 1200 mg every 2 weeks thereafter. 2
For pediatric patients, dosing is weight-based: patients 40+ kg receive adult dosing; 30-40 kg receive 600 mg weekly × 2 doses then 900 mg maintenance; 20-30 kg receive 600 mg weekly × 2 doses then 600 mg maintenance; 10-20 kg receive 600 mg × 1 dose then 300 mg maintenance; 5-10 kg receive 300 mg × 1 dose then 300 mg every 3 weeks. 2
Critical Pre-Treatment Requirements
Vaccinate against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks before starting complement inhibitors. 1, 2
If urgent therapy cannot be delayed for vaccination, administer antibacterial prophylaxis immediately and vaccinate as soon as possible. 2
Patients remain at increased risk for invasive meningococcal disease even after vaccination due to complement inhibition. 2
Concurrent Supportive Management
Provide red blood cell transfusions according to standard guidelines for symptomatic anemia. 1
Avoid platelet transfusions unless life-threatening bleeding occurs, as they may worsen thrombotic microangiopathy. 1
Manage acute kidney injury with renal replacement therapy if indicated, addressing electrolyte imbalances, fluid overload, and hypertension. 3
Diagnostic Confirmation (Performed Concurrently, Not Delaying Treatment)
Obtain ADAMTS13 activity level to exclude thrombotic thrombocytopenic purpura (TTP); ADAMTS13 <10% indicates TTP rather than aHUS. 4
Perform stool testing for Shiga toxin/E. coli O157 to exclude STEC-HUS; positive stool testing with diarrhea onset 4-5 days before HUS symptoms indicates STEC-HUS. 4
Order complement testing (C3, C4, CH50, complement factor antibodies) and genetic testing for complement pathway mutations, though these results should not delay treatment initiation. 1, 4
Confirm peripheral blood smear shows schistocytes >1%, though their absence does not exclude early TMA due to low test sensitivity. 4
Monitoring Treatment Response
Assess platelet count normalization (target >150,000/mm³) every 2-4 weeks until doses are stabilized. 1
Monitor for resolution of hemolysis by tracking LDH normalization and disappearance of schistocytes on peripheral smear. 1
Evaluate stabilization or improvement in renal function through serial creatinine measurements. 1
In pediatric patients, interpret creatinine levels relative to age-appropriate norms, as up to 50% of newborns with aHUS may present without all three classic triad components. 4
Special Clinical Contexts
For pregnancy-triggered aHUS, initiate C5 inhibitors immediately, as these have been instrumental in resolving TMA in pregnant women. 1
In patients undergoing plasmapheresis, plasma exchange, or fresh frozen plasma infusion, provide supplemental dosing of complement inhibitors according to FDA-approved protocols. 2
For patients being evaluated for kidney transplantation, maintain complement inhibitor therapy to prevent aHUS recurrence in the transplanted kidney, as renal transplantation can trigger disease recurrence or de novo aHUS. 1
Long-Term Management Considerations
Discontinuing complement inhibitor therapy carries a 10-20% risk of disease relapse with potential renal failure, requiring thorough risk assessment before any treatment discontinuation. 1
Patients require lifelong monitoring for signs of relapse, including clinical presentation changes, laboratory abnormalities, and appearance of glomerular proteinuria. 1
Offer genetic counseling to patients with confirmed aHUS diagnosis due to possible genetic transmission patterns. 1
Be aware that patients of Chinese or Japanese descent may not respond to C5 inhibitors due to polymorphic variants of the C5 gene. 1
Critical Pitfalls to Avoid
Never delay eculizumab/ravulizumab therapy while awaiting genetic testing results, as this is a medical emergency requiring immediate intervention. 1, 4
Do not discontinue complement inhibitor therapy prematurely without comprehensive risk stratification, as relapse rates are significant. 1
Ensure enrollment in the ULTOMIRIS and SOLIRIS REMS program, as these medications are only available through this restricted distribution system. 2
Monitor patients continuously for early signs of meningococcal infection and evaluate immediately if infection is suspected, as these infections can become rapidly life-threatening. 2