Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
BMC Nephrol. 2024 Jul 15;25(1):224. doi: 10.1186/s12882-024-03662-3.
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.
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.
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.
尚无报道显示抗 C5 单克隆抗体治疗前后，补体介导的非典型溶血尿毒症综合征（aHUS）患者的组织学变化。在此，我们报告一例罕见的补体因子 H（CFH）基因突变合并抗 CFH 抗体的补体介导的 aHUS 病例，该患者进行了多次肾脏活检。
一名 53 岁女性因 CFH 基因突变 [c.3572C>T（p. Ser1191 Leu）] 和抗 CFH 抗体而发生 aHUS，其父亲在 30 多岁时因急性肾损伤（AKI）去世。她表现为 AKI、血小板减少症和伴有裂体细胞的溶血性贫血。在用 1 次血浆置换提高血小板计数后，在症状发作后 1 个月进行了肾脏活检。在肾小球和小动脉中发现血管血栓形成、明显的内皮肿胀、毛细血管内细胞增生和 subendothelial 渗出性病变。立即使用依库珠单抗进行抗 C5 单克隆抗体治疗，使疾病活动迅速改善。3 个月后进行的第二次活检显示内皮损伤明显改善，仍有膜双轮廓和渗出性病变。在肾功能逐渐改善 17 个月后进行的第三次活检显示，双轮廓进一步减少，同时渗出性病变改变为纤维内膜增厚。
这是首例通过展示抗 C5 单克隆抗体治疗前后的连续肾脏病理特征，报告 aHUS 肾脏发病机制和抗 C5 单克隆抗体治疗效果的病例。由于其 CFH 突变被认为是最重要的病理条件，因此以依库珠单抗为中心的治疗得以实施，从而获得了良好的长期预后。此外，在抗 C5 单克隆抗体治疗后 1 年以上，aHUS 的肾脏病理得到缓解。
