Heterogeneity in disease course and treatment response among patients with MCD/FSGS necessitates a granular evaluation of kidney tissue features. This study aimed to identify histologic and ultrastructural descriptors of structural changes most predictive of clinical outcomes in the Nephrotic Syndrome Study Network (NEPTUNE).

Forty-eight histologic (37 glomerular, 9 tubulointerstitial, 2 vascular) and 20 ultrastructural descriptors were quantified by applying the NEPTUNE Digital Pathology Scoring System to NEPTUNE kidney biopsies. Outcomes included time from biopsy to disease progression, first complete remission of proteinuria, and treatment response. Relative importance of pathology and clinical predictors was obtained from random forest models, and predictive discrimination was assessed.

Among 224 participants (34% Black, 24% Hispanic), model performance was excellent, with predictive discrimination of 0.9 for disease progression, 0.85 for complete remission, and 0.81 for treatment response. The most predictive descriptors of outcomes included both conventional—e.g., global sclerosis or segmental sclerosis and interstitial fibrosis/tubular atrophy—and novel features, including adhesion, interstitial foam cells, deflation, periglomerular fibrosis, mononuclear white blood cells, endothelial cell abnormalities, microvillous transformation, and acute tubular injury.

The most predictive descriptors of clinical outcomes among MCD/FSGS patients reflected structural changes in multiple renal compartments. Reporting these descriptors should be standardized to guide prognostication of proteinuric glomerular diseases.

MCD/FSGS 患者病程和治疗反应的异质性需要对肾组织特征进行精细评估。本研究旨在确定肾病综合征研究网络 (NEPTUNE) 中最能预测临床结果的结构变化的组织学和超微结构描述符。

通过将 NEPTUNE 数字病理学评分系统应用于 NEPTUNE 肾活检，对 48 种组织学描述符（37 种肾小球、9 种肾小管间质、2 种血管）和 20 种超微结构描述符进行了量化。结果包括从活检到疾病进展的时间、蛋白尿首次完全缓解以及治疗反应。从随机森林模型中获得病理学和临床预测因子的相对重要性，并评估预测歧视。

在 224 名参与者（34% 黑人、24% 西班牙裔）中，模型表现出色，疾病进展的预测判别率为 0.9，完全缓解的预测判别率为 0.85，治疗反应的预测判别率为 0.81。最有预测性的结果描述包括传统特征（例如，整体硬化或节段性硬化和间质纤维化/肾小管萎缩）和新特征，包括粘附、间质泡沫细胞、通缩、肾小球周围纤维化、单核白细胞、内皮细胞异常、微绒毛。转化和急性肾小管损伤。

MCD/FSGS 患者临床结果最具预测性的描述符反映了多个肾区的结构变化。报告这些描述符应该标准化，以指导蛋白尿性肾小球疾病的预测。