BACKGROUND The C3 glomerulopathies (C3G) are recently defined glomerular diseases, attributed to abnormal complement regulation. Dense deposit disease (DDD) is part of the spectrum of C3G, characterized by electron-dense deposits in the lamina densa of the glomerular basement membrane. Patients with DDD present with hematuria, variable degrees of proteinuria, and kidney dysfunction. Kidney biopsies typically disclose proliferative and inflammatory patterns of injury. Treatment with glucocorticoids and mycophenolate mofetil has been shown to achieve remission of proteinuria in a significant proportion of C3G patients. CASE-DIAGNOSIS/TREATMENT We report two patients with persistent nephrotic syndrome while on immunosuppressive therapy. Repeat kidney biopsies disclosed massive C3 deposits with foot process effacement in the absence of proliferative or inflammatory lesions on light microscopy. CONCLUSION These cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.

中文翻译：

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致密性沉积病中的难治性肾病综合征：补体介导的肾小球毛细血管壁损伤？

背景技术C3肾小球病（C3G）是近来定义的肾小球疾病，归因于异常的补体调节。致密沉积病（DDD）是C3G光谱的一部分，其特征是肾小球基底膜的层状腺中存在电子致密沉积物。DDD患者存在血尿，蛋白尿程度不同和肾功能不全。肾脏活检通常显示损伤的增生和炎性模式。糖皮质激素和霉酚酸酯的治疗已显示在相当大比例的C3G患者中可减轻蛋白尿。病例诊断/治疗我们报告了两名接受免疫抑制治疗的持续性肾病综合征患者。重复进行肾脏活检，发现在光学显微镜下没有增生性或炎性病变的情况下，大量C3沉积物伴有足突消失。结论这些病例，再加上来自疾病模型的数据以及C3G患者对依库丽单抗的可变反应，说明C3G肾损伤的发生可能涉及两种不同的途径：一种独立于C5的途径导致肾小球毛细血管壁损伤以及蛋白尿的发展与导致增殖性肾小球肾炎和肾功能不全的C5依赖途径的关系。