背景:尚无报道显示非典型溶血性尿毒综合征(aHUS)患者抗C5单克隆抗体治疗前后的组织学变化。这里,我们报道了一例罕见的补体介导的aHUS患者,其具有补体因子H(CFH)突变和抗CFH抗体,该患者接受了多次肾脏活检.
方法:一名53岁的女性患有CFH基因突变的aHUS[c.3572C>T(p。Ser1191Leu)]和抗CFH抗体。她的父亲在30年代死于急性肾损伤(AKI)。她表现出AKI,血小板减少症,和溶血性贫血与分裂细胞。通过一次血浆置换改善血小板计数后,症状出现后1个月进行肾活检.血管血栓形成,明显的内皮肿胀,毛细血管内细胞增多,并检测到肾小球和小动脉的内皮下渗出性病变。使用依库珠单抗的抗C5单克隆抗体治疗立即改善了疾病活动性。3个月后的第二次活检显示,内皮损伤的显着改善,残留的膜双轮廓和渗出性病变。肾功能逐渐改善后17个月的第三次活检显示,双重轮廓进一步减少,渗出性病变改变为纤维内膜增厚。
结论:这是首次通过在抗C5单克隆抗体治疗之前和之后呈现一系列肾脏病理特征来显示aHUS在肾脏中的病理生理学和抗C5单克隆抗体治疗的功效的报告。由于她的CFH突变被认为是最重要的病理状况,以依库珠单抗为中心的治疗,导致良好的长期预后。此外,aHUS的肾脏病理学消退发生在抗C5单克隆抗体治疗后1年以上.
BACKGROUND: No
reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare
case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies.
METHODS: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening.
CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.