BACKGROUND The analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses. METHODS We investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility. We performed consensus clustering of patients to identify unique electron microscopy profiles. For both individual descriptors and clusters, we used Cox regression models to assess associations with time from biopsy to proteinuria remission and time to a composite progression outcome (≥40% decline in eGFR, with eGFR<60 ml/min per 1.73 m2, or ESKD), and linear mixed models for longitudinal eGFR measures. RESULTS Intrarater and interrater reproducibility was >0.60 for 12 out of 12 and seven out of 12 descriptors, respectively. Individual podocyte descriptors such as effacement and microvillous transformation were associated with complete remission, whereas endothelial cell and glomerular basement membrane abnormalities were associated with progression. We identified six descriptor-based clusters with distinct electron microscopy profiles and clinical outcomes. Patients in a cluster with more prominent foot process effacement and microvillous transformation had the highest rates of complete proteinuria remission, whereas patients in clusters with extensive loss of primary processes and endothelial cell damage had the highest rates of the composite progression outcome. CONCLUSIONS Systematic analysis of electron microscopic findings reveals clusters of findings associated with either proteinuria remission or disease progression.

中文翻译：

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蛋白尿患者的超微结构表征可预测临床结果。

背景技术尽管对疾病诊断有所贡献，但通过电子显微镜确定的肾小球特征的分析和报告仅限于极少具有预测价值的参数。方法我们从肾病综合症研究网络（NEPTUNE）数字病理评分系统中调查了12个电子显微镜组织学和超微结构变化（描述符）的预后价值。研究病理学家在242例最小变化疾病或FSGS患者的NEPTUNE肾活检中对12个描述符进行了评分，重复读数以评估可重复性。我们对患者进行了共识聚类，以识别独特的电子显微镜谱。对于单个描述符和群集，我们使用Cox回归模型评估从活检到蛋白尿缓解的时间与复合进展结果的时间（eGFR下降40％以上，eGFR <60 ml / min / 1.73 m2或ESKD）的相关性，以及线性混合模型纵向eGFR措施。结果对于12个描述符中的12个和12个描述符中的7个，Intrarater和interter的再现性分别> 0.60。个体的足细胞描述符，如表面污迹和微绒毛转化与完全缓解相关，而内皮细胞和肾小球基底膜异常与进展相关。我们确定了六个基于描述符的簇，具有不同的电子显微镜谱和临床结果。足突消失和微绒毛转化更为突出的患者中，蛋白尿完全缓解的发生率最高，而原发过程大量丧失和内皮细胞损伤的患者中，复合进展结果的发生率最高。结论对电子显微镜检查结果的系统分析揭示了与蛋白尿缓解或疾病进展相关的一系列发现。