Thrombotic microangiopathy after kidney transplant: a mechanistic + therapeutic decision tree

PURPOSE OF REVIEW: Posttransplant thrombotic microangiopathy (TMA) is classified as de novo or recurrent, with distinct triggers and management implications for kidney transplant recipients. This review provides an etiology-based framework for de novo TMA and the current approach to diagnosis, pretransplant risk assessment, and management of recurrent complement-mediated TMA (atypical hemolytic uremic syndrome). RECENT FINDINGS: Complement alternative pathway dysregulation underlies both de novo and recurrent posttransplant TMA, with pathogenic variants in complement regulatory proteins-factor H, complement regulatory proteins-factor I, and membrane cofactor protein identified in a substantial minority of affected recipients and increasingly sought as a second hit alongside calcineurin inhibitor exposure, antibody-mediated rejection, infection, and ischemia-reperfusion injury. Eculizumab, and increasingly ravulizumab, have transformed outcomes in complement-mediated disease, with growing evidence supporting pretransplant prophylactic use in high-recurrence-risk genotypes and protocol-based alternatives in lower-risk settings. SUMMARY: A systematic, etiology-directed approach-addressing reversible triggers, excluding rejection and infection, and reserving complement blockade for complement-mediated or refractory disease-remains central to managing posttransplant TMA, though randomized trial data to guide optimal prophylactic strategy remain limited.