Marius Wittig, Ashish Verma, Andrea Bellavia, Sophia Rosan, Sophie E Claudel, Aditya Surapaneni, Ragnar Palsson, Anand Srivastava, Isaac E Stillman, Joel M Henderson, Laurence H Beck, Jeffrey B Hodgin, Morgan E Grams, Eugene P Rhee, Tobias B Huber, Sushrut S Waikar, Insa M Schmidt
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Whether FPE, as reported on kidney biopsies, is associated with histopathologic lesions and adverse clinical outcomes across a range of kidney diseases has not yet been explored.</p><p><strong>Methods: </strong>We developed semi-quantitative scores from free text pathologists' descriptions of FPE severity, using EM reports from 813 participants in the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort study of individuals with biopsy-confirmed kidney disease. Logistic regression and accelerated failure time models were used to assess the associations of FPE severity with pathologist-adjudicated histopathologic lesions and progression to kidney failure, respectively. In exploratory analysis, we employed mediation analysis to decompose the total effect of FPE severity on kidney failure, exploring the role of measured albuminuria as a mediator in this pathway.</p><p><strong>Results: </strong>Fifty-six % of BKBC participants had no or mild FPE and 44% had moderate or severe FPE. After multivariable adjustment for age, race, sex, and eGFR, more severe mesangial expansion (OR 1.91, 95% CI 1.26 to 2.88, p=0.002) and more severe interstitial fibrosis/tubular atrophy (OR 1.60, 95% CI 1.09 to 2.33, p=0.015) were significantly associated with moderate or severe FPE. In the fully adjusted model, moderate or severe FPE was associated with a 2.7-fold higher hazard of progression to kidney failure compared to none or mild FPE (HR=2.66 (95% CI 1.91, 3.71, p<0.001). Mediation analysis showed that FPE affected kidney failure survival times through both direct effects and indirect (mediated) effects via albuminuria.</p><p><strong>Conclusions: </strong>FPE is associated not only with glomerular but also tubulointerstitial patterns of injury and may serve as a prognostic tool for assessing the risk of kidney disease progression.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Associations of Foot Process Effacement with Kidney Histopathologic Lesions and Disease Progression.\",\"authors\":\"Marius Wittig, Ashish Verma, Andrea Bellavia, Sophia Rosan, Sophie E Claudel, Aditya Surapaneni, Ragnar Palsson, Anand Srivastava, Isaac E Stillman, Joel M Henderson, Laurence H Beck, Jeffrey B Hodgin, Morgan E Grams, Eugene P Rhee, Tobias B Huber, Sushrut S Waikar, Insa M Schmidt\",\"doi\":\"10.34067/KID.0000000894\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Foot process effacement (FPE), a marker of podocyte injury observable via electron microscopy (EM), plays a key role in the pathophysiology of albuminuria and kidney disease progression. Whether FPE, as reported on kidney biopsies, is associated with histopathologic lesions and adverse clinical outcomes across a range of kidney diseases has not yet been explored.</p><p><strong>Methods: </strong>We developed semi-quantitative scores from free text pathologists' descriptions of FPE severity, using EM reports from 813 participants in the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort study of individuals with biopsy-confirmed kidney disease. Logistic regression and accelerated failure time models were used to assess the associations of FPE severity with pathologist-adjudicated histopathologic lesions and progression to kidney failure, respectively. In exploratory analysis, we employed mediation analysis to decompose the total effect of FPE severity on kidney failure, exploring the role of measured albuminuria as a mediator in this pathway.</p><p><strong>Results: </strong>Fifty-six % of BKBC participants had no or mild FPE and 44% had moderate or severe FPE. After multivariable adjustment for age, race, sex, and eGFR, more severe mesangial expansion (OR 1.91, 95% CI 1.26 to 2.88, p=0.002) and more severe interstitial fibrosis/tubular atrophy (OR 1.60, 95% CI 1.09 to 2.33, p=0.015) were significantly associated with moderate or severe FPE. In the fully adjusted model, moderate or severe FPE was associated with a 2.7-fold higher hazard of progression to kidney failure compared to none or mild FPE (HR=2.66 (95% CI 1.91, 3.71, p<0.001). Mediation analysis showed that FPE affected kidney failure survival times through both direct effects and indirect (mediated) effects via albuminuria.</p><p><strong>Conclusions: </strong>FPE is associated not only with glomerular but also tubulointerstitial patterns of injury and may serve as a prognostic tool for assessing the risk of kidney disease progression.</p>\",\"PeriodicalId\":17882,\"journal\":{\"name\":\"Kidney360\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney360\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34067/KID.0000000894\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney360","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34067/KID.0000000894","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：足突消退（FPE）是通过电子显微镜（EM）观察到的足细胞损伤标志物，在蛋白尿和肾脏疾病进展的病理生理中起关键作用。肾活检报告的FPE是否与一系列肾脏疾病的组织病理学病变和不良临床结果相关，目前尚未探讨。方法：我们利用波士顿肾活检队列（BKBC）中813名参与者的EM报告，从病理学家对FPE严重程度的描述中获得半定量评分，BKBC是一项针对活检证实的肾脏疾病个体的前瞻性队列研究。分别使用逻辑回归和加速衰竭时间模型来评估FPE严重程度与病理学判定的组织病理学病变和肾衰竭进展之间的关系。在探索性分析中，我们采用中介分析来分解FPE严重程度对肾衰竭的总影响，探索尿白蛋白在这一途径中的中介作用。结果：56%的BKBC参与者没有或轻度FPE， 44%有中度或重度FPE。在对年龄、种族、性别和eGFR进行多变量调整后，更严重的系膜扩张（OR 1.91, 95% CI 1.26至2.88,p=0.002）和更严重的间质纤维化/小管萎缩（OR 1.60, 95% CI 1.09至2.33,p=0.015）与中度或重度FPE显著相关。在完全调整的模型中，中度或重度FPE与无或轻度FPE相比，进展为肾衰竭的风险高2.7倍（HR=2.66） （95% CI 1.91, 3.71）。结论：FPE不仅与肾小球损伤模式相关，还与小管间质损伤模式相关，可以作为评估肾脏疾病进展风险的预后工具。
The Associations of Foot Process Effacement with Kidney Histopathologic Lesions and Disease Progression.
Background: Foot process effacement (FPE), a marker of podocyte injury observable via electron microscopy (EM), plays a key role in the pathophysiology of albuminuria and kidney disease progression. Whether FPE, as reported on kidney biopsies, is associated with histopathologic lesions and adverse clinical outcomes across a range of kidney diseases has not yet been explored.
Methods: We developed semi-quantitative scores from free text pathologists' descriptions of FPE severity, using EM reports from 813 participants in the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort study of individuals with biopsy-confirmed kidney disease. Logistic regression and accelerated failure time models were used to assess the associations of FPE severity with pathologist-adjudicated histopathologic lesions and progression to kidney failure, respectively. In exploratory analysis, we employed mediation analysis to decompose the total effect of FPE severity on kidney failure, exploring the role of measured albuminuria as a mediator in this pathway.
Results: Fifty-six % of BKBC participants had no or mild FPE and 44% had moderate or severe FPE. After multivariable adjustment for age, race, sex, and eGFR, more severe mesangial expansion (OR 1.91, 95% CI 1.26 to 2.88, p=0.002) and more severe interstitial fibrosis/tubular atrophy (OR 1.60, 95% CI 1.09 to 2.33, p=0.015) were significantly associated with moderate or severe FPE. In the fully adjusted model, moderate or severe FPE was associated with a 2.7-fold higher hazard of progression to kidney failure compared to none or mild FPE (HR=2.66 (95% CI 1.91, 3.71, p<0.001). Mediation analysis showed that FPE affected kidney failure survival times through both direct effects and indirect (mediated) effects via albuminuria.
Conclusions: FPE is associated not only with glomerular but also tubulointerstitial patterns of injury and may serve as a prognostic tool for assessing the risk of kidney disease progression.
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