A New Paradigm for Renal Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia and microangiopathic hemolytic anemia, results from acute and/or chronic endothelial cell injury, and often manifests with kidney dysfunction. TMA can be observed in a wide spectrum of clinical scenarios, which includes but is not limited to thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, severe (malignant) hypertension, preeclampsia/eclampsia, antiphospholipid antibody syndrome, scleroderma renal crisis, drug toxicities, or metabolic disorders. These different conditions are impossible to distinguish based solely on the pathologic findings, necessitating correlation with clinical and laboratory data. For both treating physicians and pathologists, the absence of specific pathologic features for a particular etiology or association with TMA remains a great source of frustration and confusion that currently accompanies this complex topic. In this review, we introduce a new paradigm for TMA that coalesces around the important contribution of the complement system, which has potential implications for therapeutic management, disease recurrence in the kidney allograft, and genetic risks to family members.