Békássy Zivile D, Kristoffersson Ann-Charlotte, Cronqvist Mats, Roumenina Lubka T, Rybkine Tania, Vergoz Laura, Hue Christophe, Fremeaux-Bacchi Veronique, Karpman Diana
Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
Nephrol Dial Transplant. 2013 Nov;28(11):2899-907. doi: 10.1093/ndt/gft340. Epub 2013 Sep 5.
Atypical haemolytic uraemic syndrome (aHUS) is associated with dysfunction of the alternative pathway of complement. Disease activity subsides as renal failure progresses but recurs upon renal transplantation, indicating that viable renal tissue contributes to disease activity. We present evidence of cerebrovascular occlusive disease indicating that vascular injury may occur in the absence of kidneys.
A currently 12-year-old girl developed renal failure at the age of 20 months. She underwent bilateral nephrectomy and renal transplantation but lost the transplant due to recurrences. She was on haemodialysis for 7 years. At 10 years of age she developed a transient ischaemic attack. Imaging, genetic investigation and mutation characterization were performed.
Imaging demonstrated occlusion and stenosis of the carotid arteries. Two complement mutations, a novel mutation in factor B and a previously described mutation in factor I, and the H3-factor H haplotype, were identified. The factor B mutation, L433S, did not induce excessive complement activation in vitro. Measurement of C3 degradation products indicated ongoing complement activation. In spite of the patient being anephric, treatment was initiated with eculizumab, a humanized anti-C5 antibody that blocks terminal complement activation. She underwent a successful kidney transplant 9 months later and has not developed a recurrence or progression of vascular stenosis 1 year later.
The course of disease in this patient with aHUS suggests that complement-mediated vascular injury may occur in the total absence of renal tissue and overt recurrences. To our knowledge, this is the first description of eculizumab treatment in an anephric aHUS patient.
非典型溶血尿毒综合征（aHUS）与补体替代途径功能障碍相关。随着肾衰竭进展，疾病活动度会消退，但在肾移植后会复发，这表明存活的肾组织会导致疾病活动。我们提供了脑血管闭塞性疾病的证据，表明在没有肾脏的情况下也可能发生血管损伤。
一名目前12岁的女孩在20个月大时出现肾衰竭。她接受了双侧肾切除术和肾移植，但因复发而失去了移植肾。她接受了7年的血液透析。10岁时，她发生了一次短暂性脑缺血发作。进行了影像学检查、基因检测和突变特征分析。
影像学检查显示颈动脉闭塞和狭窄。鉴定出两个补体突变，一个是因子B的新突变和一个先前描述的因子I突变，以及H3-因子H单倍型。因子B突变L433S在体外未诱导过度的补体激活。C3降解产物的测量表明补体持续激活。尽管患者无肾，但开始使用依库珠单抗治疗，这是一种阻断补体末端激活的人源化抗C5抗体。9个月后她成功进行了肾移植，1年后未出现血管狭窄的复发或进展。
该aHUS患者的病程表明，在完全没有肾组织和明显复发的情况下，补体介导的血管损伤可能会发生。据我们所知，这是首次对无肾aHUS患者进行依库珠单抗治疗的描述。
