Outscoring Current Classification Systems for Nephrotic Syndrome.
Outscoring Current Classification Systems for Nephrotic Syndrome.
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超越当前肾病综合征分类系统。
DOI：
10.1053/j.ajkd.2021.12.005
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Lin,Jennie
中科院分区：
文献类型：
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作者：
Hall,Gentzon;Lin,Jennie
局灶节段性肾小球硬化（FSGS）和最小改变病（MCD）分别占美国成人和儿童肾病综合征诊断的大多数。1,2虽然通常被称为疾病，但FSGS和MCD实际上是以肾小球上皮细胞损伤和滤过屏障缺陷为特征的组织学损伤模式。临床上，FSGS和MCD均可表现为肾小球病理异质性和治疗反应不一的肾病综合征。由于与这些表型相关的高度可变性，我们目前的分类系统依赖于少数形态学特征，不能完全解释临床病理表现的范围。这些限制对诊断和预测的准确性以及合理治疗方法的发展提出了挑战。迫切需要新的方法来提高我们对肾病综合征的诊断能力。通过使用综合结构和分子组织病理学分析来完善目前的FSGS和MCD分类方案，可以提高我们对肾小球疾病的诊断和预后能力，并增强我们对肾病综合征足细胞功能障碍和肾小球损伤机制的理解。在这一期的AJKD中，Hodgin等人提出了一种新的肾小球疾病评分系统，将FSGS和MCD患者分为亚组，将组织学特征与临床结果和分子表型联系起来，而我们目前的疾病分类系统未包括这些特征。作者假设，量化疾病相关的结构和分子变化将揭示这些患者亚群的临床和生物学特征信息。目前的免疫抑制疗法并不能对所有FSGS和MCD患者实现蛋白尿的持久缓解和肾功能的持续保护，5,6表明某些亚组患者可能具有不同的分子过程驱动其疾病的病理生理。换句话说，在治疗FSGS和MCD时，一种方法肯定不适合所有人。因此，在分子谱和更详细的肾小球结构变化评分评估的支持下，将患者分为亚组，可以更好地为未来的机制研究和临床试验提供精准医疗的信息。
Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) account for a majority of nephrotic syndrome diagnoses in US adults and children, respectively. 1, 2 Although commonly referred to as diseases, FSGS and MCD are, in fact, histologic injury patterns characterized by glomerular epithelial cell damage and filtration barrier defects. Clinically, both FSGS and MCD can manifest in nephrotic syndrome with heterogeneous glomerular pathology and variable responses to therapy. 3 Owing to the high degree of variability associated with these phenotypes, our current classification systems, which rely on a handful of morphologic characteristics, do not fully account for the range of clinicopathologic presentations. These limitations pose challenges to the accuracy of diagnosis and prognostication, and to the development of rational therapeutics. There is an urgent unmet need for novel approaches to enhance our diagnostic capabilities for nephrotic syndrome. Refinement of the current FSGS and MCD classification scheme through the use of integrated structural and molecular histopathologic analyses may improve our diagnostic and prognostic capabilities in glomerular disease and enhance our understanding of the mechanisms of podocyte dysfunction and glomerular injury in nephrotic syndrome. In this issue of AJKD, Hodgin et al4 present a novel glomerular disease scoring system to categorize FSGS and MCD patients into subgroups, linking histologic features with clinical outcomes and molecular phenotypes not included in our current disease classification systems. The authors hypothesize that quantification of disease-relevant structural and molecular changes would reveal clinically and biologically distinctive information for these patient subgroups. Current immunosuppressive therapies do not achieve durable remission of proteinuria and sustained preservation of kidney function for all FSGS and MCD patients, 5, 6 suggesting that some subgroups of patients may have differing molecular processes driving the pathophysiology of their disease. In other words, one size most certainly does not fit all in treating FSGS and MCD. Thus, patient classification into subgroups supported by molecular profiling and more detailed, scored evaluation of glomerular structural changes may better inform precision medicine efforts in future mechanistic studies and clinical trials.