Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis
Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis
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DOI：
10.34067/kid.0000812022
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发表时间：
2022-08-25
期刊：
影响因子：
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通讯作者：
Nozu, Kandai
中科院分区：
文献类型：
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作者：
Nagano, China;Hara, Shigeo;Nozu, Kandai
背景：大约30%的类固醇抵抗性肾病综合征（SRNS）患儿有致病性单基因变异。SRNS代表由各种病因引起的肾小球疾病，这些病因导致肾小球损伤的模式相似。SRNS患者主要表现为局灶节段性肾小球硬化（FSGS）。关于FSGS的组织学变异（使用哥伦比亚分类诊断）与单基因变异检出率或临床特征之间的关系的信息有限。在这里，我们报告了大量受影响患者的FSGS特征。方法回顾性分析119例FSGS患者，采用哥伦比亚分级法诊断；所有患者均于2016年至2021年转诊至我院进行基因检测。我们使用包括62个足细胞相关基因的靶向下一代测序面板对所有患者进行了全面的基因筛选。有关患者的临床特征和病理表现的数据来自转诊临床医生。我们分析了组织学变异与临床特征、肾脏存活率和基因变异检出率的关系。结果根据哥伦比亚分类的组织学变异分布为：未注明的FSGS占45% (n=53)，细胞型占21% (n=25)，门周型占15% (n=18)，塌陷型占13% (n=16)，尖端型占6% （n=7）。终末期肾病发病的中位年龄为37岁；变异之间的发病年龄没有差异。我们在34%（119人中的40人）的患者中检测到涉及12个筛选足细胞相关基因的单基因致病变异。最常见的基因是WT1（23%）、INF2（20%）、TRPC6（20%）和ACTN4（10%）。门周变异和尖端变异与单基因变异的相关性最强和最弱（分别为83%和0%，P < 0.001）。结论：我们揭示了遗传性FSGS和非遗传性FSGS在大量患者群体中的组织学变异分布。有关基因变异和病理结果的详细资料对了解FSGS的病因非常重要。
Background Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients. Methods This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates. Results The distribution of histologic variants according to the Columbia classification was 45% (n=53) FSGS not otherwise specified, 21% (n=25) cellular, 15% (n=18) perihilar, 13% (n=16) collapsing, and 6% (n=7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P < 0.001). Conclusions We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS.