Servais Aude, Noël Laure-Hélène, Frémeaux-Bacchi Véronique, Lesavre Philippe
Department of a Nephrology, Service de Néphrologie adultes, Hôpital Necker, 149, rue de Sèvres, FR–75015 Paris, France.
Contrib Nephrol. 2013;181:185-93. doi: 10.1159/000348654. Epub 2013 May 8.
C3 glomerulopathy is a recent disease classification comprising several rare types of glomerulonephritis, including dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The most common histological feature in these diseases is the presence of glomerular deposition of C3 within the mesangium and along the glomerular basement membrane (GBM) in the subendothelial area or within the GBM. The key role of complement alternative pathway (AP) in these disorders has been recently shown with the identification of acquired or genetic abnormalities. Low serum C3 level but normal C4 is a common finding. The acquired AP dysregulation in DDD and C3GN may be first induced by C3 nephritic factor (C3NeF). C3NeF activity is found in approximately 80% of patients with DDD and in 45% of patients with C3GN. The correlation with the complement is further supported by the detection of homozygous or heterozygous mutations in the regulatory complement proteins factor H (CFH), factor I (CFI), or C3. The genetic background of the patients may also influence the disease manifestation since common genetic variants including single nucleotide polymorphisms in the CFH, C3 and CFHR5 genes are associated with DDD and one at-risk MCP haplotype have been found to be significantly increased in C3GN. C3 glomerulopathies can present over a broad age range. DDD is more often diagnosed in children and age at diagnosis is significantly higher for patients with C3GN. Presenting features comprise any of proteinuria, hematuria, hypertension and renal failure. These glomerulonephritides are associated with chronic deterioration of renal function, leading to ESRD within 10 years of the diagnosis in 36-50% of patients. Outcomes of renal transplantation are characterized by histological recurrence which may contribute to increased rates of allograft failure. Administration of recombinant FH if it becomes available or replacement of FH via plasma exchange may be efficacious in the cases of FH deficiency. However, therapeutic inhibition of complement C3 and C5 is the main perspective.
C3肾小球病是一种新的疾病分类，包括几种罕见类型的肾小球肾炎，如致密物沉积病（DDD）和C3肾小球肾炎（C3GN）。这些疾病最常见的组织学特征是C3在系膜内以及在内皮下区域的肾小球基底膜（GBM）内或GBM内沿肾小球基底膜沉积。补体替代途径（AP）在这些疾病中的关键作用最近已通过获得性或遗传性异常的鉴定得到证实。血清C3水平低但C4正常是常见表现。DDD和C3GN中获得性AP失调可能首先由C3肾炎因子（C3NeF）诱导。在大约80%的DDD患者和45%的C3GN患者中发现C3NeF活性。补体调节蛋白因子H（CFH）、因子I（CFI）或C3中的纯合或杂合突变的检测进一步支持了与补体的相关性。患者的遗传背景也可能影响疾病表现，因为包括CFH、C3和CFHR5基因中的单核苷酸多态性在内的常见遗传变异与DDD相关，并且已发现一种高危MCP单倍型在C3GN中显著增加。C3肾小球病可在广泛的年龄范围内出现。DDD在儿童中更常被诊断，C3GN患者的诊断年龄明显更高。临床表现包括蛋白尿、血尿、高血压和肾衰竭中的任何一种。这些肾小球肾炎与肾功能的慢性恶化相关，在36%至50%的患者中，诊断后10年内会导致终末期肾病（ESRD）。肾移植的结果以组织学复发为特征，这可能导致移植失败率增加。如果有重组FH可用，给予重组FH或通过血浆置换替代FH在FH缺乏的情况下可能有效。然而，补体C3和C5的治疗性抑制是主要的治疗方向。
