Kidney Week Educational Symposia-Novel Insights into the Diagnosis and Management of Atypical Hemolytic Uremic Syndrome

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Video Summary

The Kidney Week 2020 session reviews major advances in diagnosing and treating thrombotic microangiopathies (TMAs), emphasizing that TTP and HUS are distinct entities and that “HUS” includes multiple causes requiring targeted workups and therapies. Atypical HUS (aHUS) is presented as a complement-mediated TMA triggered by complement-activating events (often infections; pregnancy is an important trigger in adults). Genetic defects include loss-of-function variants in complement regulators (factor H, factor I, MCP, thrombomodulin) and gain-of-function variants in C3 or factor B; emerging data also link coagulation pathways (e.g., DGKE). Clinically, aHUS commonly causes the triad of hemolysis, thrombocytopenia, and acute kidney injury, with frequent extrarenal complications and high post-transplant recurrence.<br /><br />Key diagnostics include Shiga-toxin testing, ADAMTS13 activity (before plasma exchange), complement levels/proteins, factor H autoantibodies, and genetic panels. Newer tools include complement activation fragments (e.g., soluble C5b-9) and functional assays; CH50 may help monitor complement blockade.<br /><br />Treatment has shifted from plasma therapy (with poor long-term outcomes) to complement inhibition. Anti-C5 therapy (eculizumab) rapidly improves platelets and can recover kidney function and reduce dialysis dependence; ravulizumab offers similar efficacy with 8-week dosing. Main safety concern is meningococcal infection, requiring vaccination and antibiotic prophylaxis. Discontinuation may be possible in selected patients, with relapse risk influenced by genotype. Emerging therapies target factor B or factor D (including oral agents).

Asset Subtitle

Ursula Brewster, Bradley Dixon, Eric Rondeau
Support is provided by an educational grant from Alexion Pharmaceuticals, Inc.

Keywords

thrombotic microangiopathies

atypical hemolytic uremic syndrome

thrombotic thrombocytopenic purpura

complement-mediated TMA

ADAMTS13 activity testing

Shiga toxin diagnostics

eculizumab ravulizumab anti-C5 therapy

meningococcal vaccination prophylaxis