Abstract Thrombotic microangiopathy (TMA) is a pathological condition characterized by microangiopathic hemolytic anemia, thrombocytopenia and ischemic organ dysfunction due to microvascular endothelial damage and thrombosis. It affects approximately 0.8-14% of kidney transplant recipients, and may manifest as either a recurrent or de novo disease. While systemic manifestations are commonly anticipated, kidney-limited TMA can also occur and is not rare. Histopathologic examination of allograft biopsies shows morphologic features indicating endothelial injury, and repeated episodes of TMA may result in coexisting acute and chronic lesions within the same patient. In transplant recipients, multiple triggers contribute to endothelial damage, including ischemia-reperfusion injury, antibody-mediated rejection, immunosuppressive agents (calcineurin and mTOR inhibitors) and infections. The risk is particularly important in individuals with genetic variants that dysregulate the alternative complement pathway. In de novo TMA, environmental triggers and transplant-related stressors play a central role, whereas genetic predisposition is the primary factor in recurrent cases. Notably, these mechanisms often overlap and may act synergistically. Recurrent atypical hemolytic uremic syndrome can successfully be managed with terminal complement inhibitors, and prophylactic use of eculizumab in the peri-transplant period has significantly reduced recurrence rates. Management of de novo TMA begins with the identification and removal of precipitating factors. In cases where no clear trigger is found, or when the disease proves refractory to conventional therapy, terminal complement inhibition may be an effective therapeutic option. The prognosis of recurrent TMA has improved substantially with the advent of complement targeting therapies but research is still needed to optimize management strategies.
Mirioğlu et al. (2026) studied this question.