This IPNA consensus document addresses how to diagnose and manage atypical hemolytic uremic syndrome (aHUS) and secondary thrombotic microangiopathy (TMA) in children, covering genetic aHUS, autoimmune (anti-Factor H) aHUS, aHUS in kidney transplantation, secondary TMA, and management in resource-limited settings.
A total of 51 Clinical Practice Recommendations (CPRs) and 9 Clinical Practice Points (CPPs) were produced via modified Delphi consensus (≥80% agreement threshold). Key recommendations include: prompt C5-inhibitor (eculizumab or ravulizumab) use without waiting for ADAMTS13 or genetic results; comprehensive genetic screening of all TMA-related genes at first presentation; MMF as long-term maintenance in autoimmune aHUS; prophylactic C5 inhibition within 24 hours of transplant in moderate-to-high-risk patients; and individualized C5-inhibitor discontinuation based on genetic risk, with relapse rates of 20–30% after stopping in complement mutation carriers versus 0–22% in mutation-negative patients.
Most underlying evidence is derived from case series and observational studies; formal GRADE scoring was not applied due to limited high-quality data. Recommendations for resource-limited settings are constrained by lack of access to genetic testing and C5 inhibitors in much of Africa, the Middle East, Asia, and parts of the Americas. Pregnancy-associated TMA was explicitly excluded.
Start C5 inhibitors (eculizumab or ravulizumab) promptly in any child with suspected aHUS—do not wait for genetics or ADAMTS13 results—and pair with meningococcal, Hib, and pneumococcal vaccination plus at least 2 weeks of penicillin prophylaxis. In autoimmune aHUS, begin MMF at diagnosis for long-term antibody suppression, and plan C5-inhibitor discontinuation at 6–12 months only when anti-FH antibody levels have fallen to <30% of the onset level on two serial measurements.
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