Recent advances in understanding and treating nephrotic syndrome.
Recent advances in understanding and treating nephrotic syndrome.
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DOI：
10.12688/f1000research.10165.1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Saleem M
中科院分区：
文献类型：
--
作者：
Bierzynska A;Saleem M
特发性肾病综合征(Ins)是儿童和成人最常见的肾小球疾病之一，其中心事件是足细胞损伤。INS是一种异质性疾病，治疗主要是经验性的，在许多情况下是不成功的，类固醇是最初的治疗支柱。近70%的INS儿童对类固醇有一定的反应，并被标记为类固醇敏感，其余的儿童为类固醇抵抗(也称为局灶性节段性肾小球硬化)，后一组中很大一部分是单基因突变的基础。发病率的负担是巨大的，无论是对终生慢性病患者还是对卫生服务，特别是在管理透析和移植方面。肾病综合征的靶细胞是肾小球足细胞，足细胞生物学研究在过去15年中呈爆炸式增长。遗传学和生物学理解方面的重大进步现在将临床医生和研究人员置于对疾病进行重大重新分类和测试已确定的和新颖的靶向治疗的门槛上。这种潜力是基于完整的遗传分析，深入的临床表型，以及将机制衍生生物标记物引入临床实践。INS现在可以分为具有单基因缺陷的基因和其他基因，目前已知至少有53个基因是导致INS的原因。在其他因素中，大多数可能是由免疫调节的，由一个或多个尚不清楚的循环因子的存在引起的，是否存在第三个(或更多)机械性基团仍有待发现。因此，治疗现在正朝着分离单基因病例的方向发展，以最大限度地减少免疫抑制，并进一步了解如何最好地分层并适当地指导免疫组内的免疫抑制治疗。针对足细胞这一靶细胞的治疗还处于初级阶段，但在不久的将来仍有相当大的希望。
Idiopathic nephrotic syndrome (INS) is one of the most common glomerular diseases in children and adults, and the central event is podocyte injury. INS is a heterogeneous disease, and treatment is largely empirical and in many cases unsuccessful, and steroids are the initial mainstay of therapy. Close to 70% of children with INS have some response to steroids and are labelled as steroid-‘sensitive’, and the rest as steroid-‘resistant’ (also termed focal segmental glomerulosclerosis), and single-gene mutations underlie a large proportion of the latter group. The burden of morbidity is enormous, both to patients with lifelong chronic disease and to health services, particularly in managing dialysis and transplantation. The target cell of nephrotic syndrome is the glomerular podocyte, and podocyte biology research has exploded over the last 15 years. Major advances in genetic and biological understanding now put clinicians and researchers at the threshold of a major reclassification of the disease and testing of targeted therapies both identified and novel. That potential is based on complete genetic analysis, deep clinical phenotyping, and the introduction of mechanism-derived biomarkers into clinical practice. INS can now be split off into those with a single-gene defect, of which currently at least 53 genes are known to be causative, and the others. Of the others, the majority are likely to be immune-mediated and caused by the presence of a still-unknown circulating factor or factors, and whether there is a third (or more) mechanistic group or groups remains to be discovered. Treatment is therefore now being refined towards separating out the monogenic cases to minimise immunosuppression and further understanding how best to stratify and appropriately direct immunosuppressive treatments within the immune group. Therapies directed specifically towards the target cell, the podocyte, are in their infancy but hold considerable promise for the near future.