血栓性微血管病(TMA)的特征是微血管病性溶血性贫血,由于小血管中的内皮细胞损伤和微血栓形成而发生的血小板减少和器官损伤。当发现遗传或获得性缺陷时,TMA是主要的,如非典型溶血性尿毒症综合征(aHUS)或继发于另一种疾病过程如感染的背景下,自身免疫性疾病,恶性肿瘤或药物。区分初级补体介导的过程和次级因素触发的过程对于启动及时治疗至关重要,但对临床医生来说可能是具有挑战性的。特别是在肾移植后,由于存在多种混杂因素。同样,原发性膜性肾病是一种免疫介导的肾小球疾病,与循环自身抗体(70%的病例针对M型磷脂酶A2受体(PLA2R))相关,而继发性膜性肾病与感染相关,毒品,癌症,或其他自身免疫性疾病。补体激活也被认为是原发性膜性肾病病因的可能机制;然而,尽管补充是一个潜在的共同环节,HUS和原发性膜性肾病没有一起报告。在本文中,我们描述了一例aHUS,原因是补体因子I的致病性突变,该突变是在肾移植后发生的,该患者被诊断为PLA2R抗体相关膜性肾病。我们强调了系统和全面的分析如何帮助定义aHUS的病因,建立疾病机制,并促进了依库珠单抗的及时治疗,从而恢复了他的肾功能。尽管如此,持续的抗补体治疗不能预防同种异体移植物中膜性肾病的复发.据我们所知,这是一例原发性膜性肾病合并aHUS患者在肾移植后的首次报道.
Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury occurring due to endothelial cell damage and microthrombi formation in small vessels. TMA is primary when a genetic or acquired defect is identified, as in atypical hemolytic uremic syndrome (aHUS) or secondary when occurring in the context of another disease process such as infection, autoimmune disease, malignancy or drugs. Differentiating between a primary complement-mediated process and one triggered by secondary factors is critical to initiate timely treatment but can be challenging for clinicians, especially after a kidney transplant due to presence of multiple confounding factors. Similarly, primary membranous nephropathy is an immune-mediated glomerular disease associated with circulating autoantibodies (directed against the M-type phospholipase A2 receptor (PLA2R) in 70% cases) while secondary membranous nephropathy is associated with infections, drugs, cancer, or other autoimmune diseases. Complement activation has also been proposed as a possible mechanism in the etiopathogenesis of primary membranous nephropathy; however, despite complement being a potentially common link, aHUS and primary membranous nephropathy have not been reported together. Herein we describe a case of aHUS due to a pathogenic mutation in complement factor I that developed after a kidney transplant in a patient with an underlying diagnosis of PLA2R antibody associated-membranous nephropathy. We highlight how a systematic and comprehensive analysis helped to define the etiology of aHUS, establish mechanism of disease, and facilitated timely treatment with eculizumab that led to recovery of his kidney function. Nonetheless, ongoing anti-complement therapy did not prevent recurrence of membranous nephropathy in the allograft. To our knowledge, this is the first report of a patient with primary membranous nephropathy and aHUS after a kidney transplant.