{"doi":"10.34067/kid.0000000894","title":"The Associations of Foot Process Effacement with Kidney Histopathologic Lesions and Disease Progression","abstract":"Key Points Foot process effacement (FPE) could serve as a valuable marker for assessing the risk of disease progression across various kidney pathologies. The results from this study emphasize the need for a standardized approach to FPE assessment in pathology reporting. Incorporating FPE in a standardized manner could improve prognostic accuracy and address current gaps in reporting systems for ultrastructural markers Background Foot process effacement (FPE), a marker of podocyte injury observable via electron microscopy, 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 semiquantitative scores from free-text pathologist's descriptions of FPE severity, using electron microscopy reports from 813 participants in the Boston Kidney Biopsy Cohort, 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 used 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 percentage of Boston Kidney Biopsy Cohort 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 (odds ratio, 1.91; 95% confidence interval [CI], 1.26 to 2.88; P = 0.002) and more severe interstitial fibrosis/tubular atrophy (odds ratio, 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 with none or mild FPE (hazard ratio=2.66; 95% CI, 1.91 to 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.","journal":"Kidney360","year":2025,"id":536431,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":518168,"name":"Ashish Verma","orcid":"0000-0001-9497-6327","position":1,"is_corresponding":false},{"id":368527,"name":"Andrea Bellavia","orcid":"0000-0003-4988-4532","position":2,"is_corresponding":false},{"id":1421748,"name":"Sophia Rosan","orcid":null,"position":3,"is_corresponding":false},{"id":281788,"name":"Sophie E. Claudel","orcid":"0000-0002-7695-4674","position":4,"is_corresponding":false},{"id":232664,"name":"Aditya Surapaneni","orcid":"0000-0003-4978-5980","position":5,"is_corresponding":false},{"id":313968,"name":"Ragnar Pálsson","orcid":"0000-0002-7104-9296","position":6,"is_corresponding":false},{"id":334701,"name":"Anand Srivastava","orcid":"0000-0002-8109-1420","position":7,"is_corresponding":false},{"id":281385,"name":"Isaac E. Stillman","orcid":"0000-0002-4224-5060","position":8,"is_corresponding":false},{"id":70060,"name":"Joel Henderson","orcid":"0000-0002-9178-1708","position":9,"is_corresponding":false},{"id":251675,"name":"Laurence H. Beck","orcid":"0000-0003-1482-4089","position":10,"is_corresponding":false},{"id":247035,"name":"Jeffrey B. Hodgin","orcid":"0000-0003-0534-3048","position":11,"is_corresponding":false},{"id":73169,"name":"Morgan E. Grams","orcid":"0000-0002-4430-6023","position":12,"is_corresponding":false},{"id":350961,"name":"Katherine P. Liao","orcid":"0000-0002-4797-3200","position":13,"is_corresponding":false},{"id":234880,"name":"Tobias B. Huber","orcid":"0000-0001-7175-5062","position":14,"is_corresponding":false},{"id":34473,"name":"Sushrut S. Waikar","orcid":"0000-0003-4004-326X","position":15,"is_corresponding":false},{"id":361912,"name":"Insa M. Schmidt","orcid":"0000-0002-0420-6570","position":16,"is_corresponding":false},{"id":1421747,"name":"Maren Wittig","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:52:05.227140Z","pmid":"40728890","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}