Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Pediatr Nephrol. 2018 Dec;33(12):2289-2298. doi: 10.1007/s00467-018-4034-z. Epub 2018 Sep 20.
Membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerulopathy in children. Recently, a new classification based on immunohistological features has been established. Infections and anomalies in complement-regulating genes, leading to alternative complement pathway activation, are suspected to trigger the disease. Nevertheless, little is known about optimal treatment and outcome in children with immune-complex-MPGN (IC-MPGN) and C3-glomerulopathy (C3G).
The method used is retrospective analysis of clinical, histological, and genetic characteristics of 14 pediatric patients with MPGN in two medical centers.
Mean age of the patients was 10.6 ± 4.5 years. Patients were grouped into C3G (n = 6) and IC-MPGN (n = 8). One patient showed a likely pathogenic variant in the CFHR5 gene. All 10 patients had risk polymorphisms in complement-regulating genes. Most patients were treated with ACE inhibition, steroids, and mycophenolate mofetil. Three patients with C3G received eculizumab. Median follow-up was 2.3 years. After 1 year of disease, three patients (two C3G, one IC-MPGN) reached complete, five patients partial (three IC-MPGN, two C3G), and five patients no remission (four IC-MPGN, one C3G). One patient progressed to end-stage renal disease (ESRD) 6 years after disease onset.
IC-MPGN and C3G are rare disorders in children. Most patients have signs of complement activation associated with risk polymorphisms or likely pathogenic variants in complement-regulating genes. Steroids and mycophenolate mofetil seem to be effective and for some patients, eculizumab might be a treatment option. Outcome is heterogeneous and precise differentiation between IC-MPGN and C3G is still pending.
膜增生性肾小球肾炎（MPGN）是儿童肾小球疾病的罕见病因。最近，根据免疫组织化学特征建立了一种新的分类。感染和补体调节基因异常导致替代补体途径激活，被怀疑引发该疾病。然而，对于免疫复合物型 MPGN（IC-MPGN）和 C3 肾小球病（C3G）患儿，我们对其最佳治疗方法和预后知之甚少。
该研究采用回顾性分析两家医学中心的 14 例 MPGN 儿科患者的临床、组织学和遗传特征。
患者的平均年龄为 10.6±4.5 岁。患者分为 C3G（n=6）和 IC-MPGN（n=8）。1 例患者在 CFHR5 基因中存在可能的致病性变异。所有 10 例患者均存在补体调节基因的风险多态性。大多数患者接受 ACE 抑制剂、类固醇和霉酚酸酯治疗。3 例 C3G 患者接受依库珠单抗治疗。中位随访时间为 2.3 年。疾病 1 年后，3 例患者（2 例 C3G，1 例 IC-MPGN）达到完全缓解，5 例患者部分缓解（3 例 IC-MPGN，2 例 C3G），5 例患者未缓解（4 例 IC-MPGN，1 例 C3G）。1 例患者在疾病发病后 6 年进展为终末期肾病（ESRD）。
IC-MPGN 和 C3G 在儿童中较为罕见。大多数患者存在补体激活迹象，伴有补体调节基因的风险多态性或可能的致病性变异。类固醇和霉酚酸酯似乎有效，对于某些患者，依库珠单抗可能是一种治疗选择。预后存在异质性，IC-MPGN 和 C3G 的精确区分仍有待进一步研究。
