{"doi":"10.1101/2025.08.25.25334374","title":"Development of a Flexible Multiplex Urine RNA Assay for Detection and Differentiation of Kidney Allograft Injury","abstract":"Non-invasive approaches to detect kidney graft injury and distinguish donor-specific immune-mediated injury from other causes of inflammation are needed to guide recipient therapy while avoiding the morbidities of transplant biopsies. We used a multi-plex platform to interrogate RNA isolated from kidney transplant recipient urine to investigate gene expression patterns distinguishing grafts with no injury vs. ongoing injury and further differentiate acute T cell-mediated rejection (TCMR) from BK virus nephropathy (BKVN). As a training set we quantified expression of 796 immune function genes from 25 control recipients with stable graft function, 17 with biopsy-proven acute TCMR, and 13 with biopsy-proven BKVN. We identified a 20-gene signature that differentiated intragraft injury from grafts with stable function (area under the curve (AUC), 0.991) and a distinct 40-gene signature distinguishing acute TCMR from BKVN (AUC = 1.00). Validation in separate 118 urine RNA samples obtained at time of surveillance or for-cause biopsies from Clinical Trials in Organ Transplantation (CTOT) -08 and CTOT-19 studies showed AUC of 0.77 for the 20-gene injury signature and AUC of 0.79 for the 40-gene signature. Our results highlight the utility of this flexible, non-invasive biomarker platform for rapid detection and differentiation of immune processes causing ongoing kidney graft injury.","journal":"medRxiv","year":2025,"id":573518,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":1480732,"name":"Wenji Xu","orcid":null,"position":1,"is_corresponding":false},{"id":717329,"name":"Anna A. Zmijewska","orcid":null,"position":2,"is_corresponding":false},{"id":1480733,"name":"Dajana Margeta","orcid":null,"position":3,"is_corresponding":false},{"id":108992,"name":"Jonathan S. Bromberg","orcid":"0000-0002-1407-8795","position":4,"is_corresponding":false},{"id":56887,"name":"John J. Friedewald","orcid":"0000-0002-9344-9928","position":5,"is_corresponding":false},{"id":431625,"name":"Michaël Abécassis","orcid":"0000-0001-9333-463X","position":6,"is_corresponding":false},{"id":487906,"name":"Kenneth A. Newell","orcid":"0000-0003-4766-1888","position":7,"is_corresponding":false},{"id":489275,"name":"Yvonne Morrison","orcid":null,"position":8,"is_corresponding":false},{"id":286080,"name":"Nancy D. Bridges","orcid":"0000-0002-1140-5201","position":9,"is_corresponding":false},{"id":105288,"name":"Peter S. Heeger","orcid":"0000-0003-4673-6913","position":10,"is_corresponding":false},{"id":320236,"name":"Roslyn B. Mannon","orcid":"0000-0003-1776-3680","position":11,"is_corresponding":false},{"id":72293,"name":"Robert L. Fairchild","orcid":"0000-0002-7107-5259","position":12,"is_corresponding":false},{"id":402220,"name":"Karen S. Keslar","orcid":"0000-0001-8609-4797","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:57:32.445190Z","pmid":"41030938","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":[]}