Post Kidney Transplant Thrombotic Microangiopathy: A Narrative Review of the Challenges and Opportunities

Post-transplant thrombotic microangiopathy (PT-TMA) is a serious and underrecognized complication of kidney transplantation, associated with substantially reduced allograft survival. Its heterogeneous presentations, ranging from systemic to renal-limited forms, and multifactorial etiologies complicate timely diagnosis and management. Complement activation is central across all etiologies, either as a primary driver of disease in recurrent complement-mediated TMA (also known as atypical hemolytic uremic syndrome or aHUS) or as an amplifier in de novo PT-TMA (dnTMA). Accurate diagnosis requires a combination of clinical assessment, laboratory evaluation, and histopathologic examination, with particular attention to complement abnormalities, donor/recipient risk factors, and potential triggers. Management must be individualized, encompassing supportive care, optimization of immunosuppression, complement blockade, and plasmapheresis in select cases. Histologic features and clinical risk factors can guide prognosis, and scoring systems provide valuable tools for risk stratification. Despite advances in therapy, long-term outcomes remain suboptimal, particularly in antibody-mediated rejection (AMR)-related cases. Ongoing research is essential to clarify the optimal context for the use of anti-complement therapy, and to develop effective prophylactic and therapeutic strategies while maintaining adequate immunosuppression.