Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis
Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis
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DOI：
10.2215/cjn.12901211
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发表时间：
2012-05-01
影响因子：
9.8
通讯作者：
Appel, Gerald B.
中科院分区：
文献类型：
--
作者：
Bomback, Andrew S.;Smith, Richard J.;Appel, Gerald B.
背景与目的致密沉积病和C3型肾小球肾炎的主要缺陷是补体通路异常活跃。Eculizumab是一种与C5结合以防止膜攻击复合物形成的单克隆抗体，可能是有益的。设计、设置、参与者和测量在这项开放标签、概念验证的疗效和安全性研究中，6名患有致密沉积物病或C3肾小球肾炎的受试者每隔一周接受eculizumab治疗1年。在入组时，所有患者均有蛋白尿/d和/或AKI。受试者在入组前接受活检，并在1年后重复活检。结果本研究包括3例致密沉积病（包括1例复发性同种异体移植致密沉积病）和3例C3肾小球肾炎（包括2例复发性同种异体移植C3肾小球肾炎）。遗传和补体功能检测显示CFH和MCP各1例突变，C3肾病因子3例，血清膜攻击复合物3例升高。12个月后，两名受试者血清肌酐明显降低，一名受试者蛋白尿明显减少，一名受试者实验室参数稳定，但组织病理学有所改善。升高的血清膜攻击复合物水平在治疗后恢复正常，同时肌酐和蛋白尿也有改善。临床和组织病理学数据表明，eculizumab对部分致密沉积病和C3肾小球肾炎患者有应答，但不是所有患者。治疗前血清膜攻击复合体的升高可以预测疗效。需要进一步的研究来确定致密沉积病/C3肾小球肾炎患者的亚组，这些患者可以考虑eculizumab治疗。中国临床医学杂志7:748-756,2012。doi: 10.2215 / CJN.12901211
Background and objectives The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial.Design, setting, participants, & measurements In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria > 1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark.Results The subjects included three patients with dense deposit disease (including one patient with recurrent dense deposit disease in allograft) and three patients with C3 glomerulonephritis (including two patients with recurrent C3 glomerulonephritis in allograft). Genetic and complement function testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic factor in three subjects, and elevated levels of serum membrane attack complex in three subjects. After 12 months, two subjects showed significantly reduced serum creatinine, one subject achieved marked reduction in proteinuria, and one subject had stable laboratory parameters but histopathologic improvements. Elevated serum membrane attack complex levels normalized on therapy and paralleled improvements in creatinine and proteinuria.Conclusions Clinical and histopathologic data suggest a response to eculizumab in some but not all subjects with dense deposit disease and C3 glomerulonephritis. Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered. Clin J Am Soc Nephrol 7: 748-756, 2012. doi: 10.2215/CJN.12901211