Background Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control.

Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay.

Results Compared with normal human serum and samples from patients with hypertensive arterionephrosclerosis, 14 of 16 (87.5%) serum samples collected at presentation from 16 patients with hypertension-associated TMA induced abnormal C5b9 formation on microvascular endothelial cells. We detected rare variants in complement genes in eight of 17 (47%) patients. ESRD occurred in 14 of 17 (82%) patients, and recurrent TMA after transplant occurred in seven of 11 (64%) donor kidneys. Eculizumab improved the renal function in three patients and prevented TMA recurrence in an allograft recipient.

Conclusions These observations point to complement defects as the key causative factor of ESRD and recurrent TMA after transplant in patients presenting with severe hypertension. Complement defects can be identified by measurements of complement activation on microvascular endothelial cells, which should substantially influence treatment and prognosis.

背景严重高血压会在肾血管中诱发血栓性微血管病（TMA），其发生与内皮的机械应力有关。伴有严重肾脏疾病并且尽管有BP控制但仍进展为ESRD的患者，补体缺陷可能是疾病的罪魁祸首。

方法我们研究了一个明确定义的队列，涉及17例高血压相关性TMA患者，以通过基于体外血清的特异性微血管内皮细胞试验确定补体缺陷的患病率。

结果与正常人血清和高血压动脉硬化患者的样品相比，从16例高血压相关TMA患者中提取的16份血清样品中有14份（87.5％）在微血管内皮细胞上诱导了异常的C5b9形成。我们在17位患者中的8位（47％）中检测到补体基因中的罕见变异。ESRD发生在17位患者中的14位（82％），移植后复发的TMA发生在11位（64％）供体肾脏中的7位。依库丽单抗改善了三名患者的肾功能，并防止了同种异体移植受者的TMA复发。

结论这些观察结果表明补充缺陷是重度高血压患者移植后ESRD和TMA复发的关键原因。补体缺陷可通过测量微血管内皮细胞上的补体激活来确定，这将显着影响治疗和预后。