Pediatric Nephrology
Pediatric Nephrology
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小儿肾脏病学
DOI：
10.1007/978-3-030-52719-8_90
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Gbadegesin R
中科院分区：
文献类型：
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作者：
Gbadegesin R
类固醇耐药肾病综合征（SRNS）是儿童终末期肾病的主要原因。基因组研究的最新发现表明，10-30%的SRNS病例是单基因疾病，其中单个基因的突变足以引起疾病。已经报道了60多个SRNS的单基因病因，实际上所有这些基因都定位于足细胞，即肾脏的肾小球内脏上皮细胞，因此称为“足细胞病”。这些基因突变导致疾病的机制尚不完全清楚;然而，新出现的数据表明，这些遗传缺陷中的一些可以破坏足细胞F-肌动蛋白细胞骨架和狭缝隔膜（SD），在SD处发出信号，并且还扰乱对足细胞正常功能至关重要的代谢活动。基因组研究的结果也为疾病的更好分类提供了信息，因此，儿童肾病综合征现在可以分为单基因NS和基于免疫的NS，而不是依赖于依赖于治疗反应和非特异性活检结果的分类法。后者的一个子集很容易被识别为循环因子疾病。这种明确定义的疾病分层对治疗方法和诊断有意义。未来的挑战包括开发在临床决策过程中利用遗传信息的平台，以及利用多组学数据和其他尖端分子平台来确定肾病综合征的新的和特定的治疗方式。
Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children. Recent findings from genomic studies suggests that 10–30% of all cases of SRNS are monogenic disease where mutation in a single gene is enough to cause disease. More than 60 single gene causes of SRNS have been reported and virtually all these genes localized to the podocyte the glomerular visceral epithelial cell of the kidney hence the term “podocytopathy.” The mechanisms by which the mutations in these genes will cause disease is not completely known; however, emerging data showed that some of these genetic defects can disrupt the podocyte F-actin cytoskeleton and the slit diaphragm (SD), signalling at the SD, and also unsettle metabolic activities that are vital for the normal function of the podocyte. Findings from genomic studies is also informing better classification of disease, thus rather than relying on taxonomy that depends on therapy response and nonspecific findings on biopsy, childhood nephrotic syndrome can now be stratified into monogenic NS and immune-based NS. A subset of the latter is readily identifiable as circulating factor disease. This clearly defined disease stratification has implications for approach to therapy and prognostication. Future challenges include developing platforms for the utilization of genetic information in clinical decision process and harnessing multi-omics data and other cutting edge molecular platforms to identify new and specific treatment modalities for nephrotic syndrome.