Eculizumab and recurrent C3 glomerulonephritis

被引:68
|
作者
Gurkan, Sevgi [1 ]
Fyfe, Billie [2 ]
Weiss, Lynne [1 ]
Xiao, Xue [3 ,4 ]
Zhang, Yuzhou [3 ,4 ]
Smith, Richard J. [3 ,4 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Div Pediat Nephrol, New Brunswick, NJ 08901 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pathol, New Brunswick, NJ 08903 USA
[3] Univ Iowa, Carver Coll Med, Dept Med, Div Nephrol & Mol Otolaryngol, Iowa City, IA 52242 USA
[4] Univ Iowa, Carver Coll Med, Renal Res Labs, Iowa City, IA 52242 USA
基金
美国国家卫生研究院;
关键词
Eculizumab; C3; Glomerulonephritis; Renal transplant; DENSE-DEPOSIT DISEASE; HEMOLYTIC-UREMIC SYNDROME; LOW-DOSE RITUXIMAB; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; ALTERNATIVE PATHWAY; ADULT PATIENTS; COMPLEMENT; GLOMERULOPATHY; MUTATION; CHILDREN;
D O I
10.1007/s00467-013-2503-y
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of dense deposit disease (DDD) and allograft recurrence of C3 glomerulonephritis (C3GN) was treated with eculizumab every other week for 1 year. The patient had pathological evidence of C3GN and proteinuria > 1 g/day at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 and 12 months. Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of the alternative pathway remained, indicating eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients.
引用
收藏
页码:1975 / 1981
页数:7
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