Severe hypertension with thrombotic microangiopathy: the need for pathogenically targeted treatments

Malignant hypertension with acute kidney injury or acute kidney disease is a life-threatening condition requiring urgent antihypertensive treatment and which carries a serious risk of kidney function loss. The presence of thrombotic microangiopathy (microangiopathic hemolytic anemia and thrombocytopenia) further challenges the diagnosis and treatment of these patients. As shown by recent studies, a high proportion of patients with complement-mediated thrombotic microangiopathy present with severe and malignant hypertension; however, extreme elevation of blood pressure by itself can induce vascular lesions of thrombotic microangiopathy. To resolve this conundrum, it is essential to rapidly investigate and exclude forms of secondary hypertension (in which hematologic features are rare) and secondary thrombotic microangiopathies, both of which require treatment of the specific underlying etiology. Definitive differentiation of essential hypertension and complement-mediated thrombotic microangiopathy requires complement genetic testing, the results of which usually take weeks to months. In this review, we analyze the clinical and histologic data that would support the diagnosis of complement-mediated thrombotic microangiopathy before the results of genetic tests, prompting the rapid initiation of complement blockers. However, there are numerous unmet gaps in the pathogenesis, diagnosis, and treatment of this disorder that require further research.