Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, 27710, USA.
Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC, 27710, USA.
Pediatr Nephrol. 2019 Nov;34(11):2279-2293. doi: 10.1007/s00467-018-4093-1. Epub 2018 Oct 2.
The pathogenesis of steroid-resistant nephrotic syndrome (SRNS) is not completely known. Recent advances in genomics have elucidated some of the molecular mechanisms and pathophysiology of the disease. More than 50 monogenic causes of SRNS have been identified; however, these genes are responsible for only a small fraction of SRNS in outbred populations. There are currently no guidelines for genetic testing in SRNS, but evidence from the literature suggests that testing should be guided by the genetic architecture of the disease in the population. Notably, most genetic forms of SRNS do not respond to current immunosuppressive therapies; however, a small subset of patients with monogenic SRNS will achieve partial or complete remission with specific immunomodulatory agents, presumably due to non-immunosuppressive effects of these agents. We suggest a pragmatic approach to the therapy of genetic SRNS, as there is no evidence-based algorithm for the management of the disease.
类固醇抵抗型肾病综合征（SRNS）的发病机制尚不完全清楚。基因组学的最新进展阐明了该疾病的一些分子机制和病理生理学。已经确定了 50 多种单基因 SRNS 的病因；然而，这些基因仅占散发病例中 SRNS 的一小部分。目前，SRNS 尚无基因检测指南，但文献中的证据表明，检测应根据人群中疾病的遗传结构进行指导。值得注意的是，大多数遗传形式的 SRNS 对当前的免疫抑制治疗无反应；然而，一小部分单基因 SRNS 患者可能会对特定的免疫调节剂产生部分或完全缓解，这可能归因于这些药物的非免疫抑制作用。我们建议对遗传 SRNS 的治疗采取务实的方法，因为目前没有针对该疾病的循证治疗算法。
