{"doi":"10.1186/s13054-024-05202-9","title":"Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes","abstract":"BACKGROUND: Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes. METHODS: We prospectively enrolled 173 ICU patients with sepsis from a suspected respiratory infection (87 without AKI and 86 with AKI on enrollment). Among the AKI patients, 66 were classified as AKI-SP1 and 20 as AKI-SP2 using a three-plasma biomarker classifier. Aptamer-based proteomics assessed 5,212 proteins in urine collected on ICU admission. We compared urinary protein abundances between AKI sub-phenotypes, conducted pathway analyses, tested associations with risk of RRT and blood bacteremia, and predicted AKI-SP2 class membership using LASSO. MEASUREMENT AND MAIN RESULTS: In total, 117 urine proteins were higher in AKI-SP2, 195 were higher in AKI-SP1 (FDR < 0.05). Urinary proteins involved in inflammation and chemoattractant of neutrophils and monocytes (CXCL1 and REG3A) and oxidative stress (SOD2) were abundant in AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), proliferation of mesenchymal cells (IL11RA), anti-inflammatory (IL10RB and TREM2) were abundant in AKI-SP1. Pathways related to immune response, complement activation and chemokine signaling were upregulated in AKI-SP2 and pathways of cell adhesion were upregulated in AKI-SP1. Overlap was present between urinary proteins that differentiated AKI sub-phenotypes and proteins that differentiated risk of RRT during hospitalization. Variable correlation was found between top aptamers and ELISA based protein assays. A LASSO derived urinary proteomic model to classify AKI-SP2 had a mean AUC of 0.86 (95% CI: 0.69-0.99). CONCLUSION: Our findings suggest AKI-SP1 is characterized by a reparative, regenerative phenotype and AKI-SP2 is characterized as an immune and inflammatory phenotype associated with blood bacteremia. We identified shared biology between AKI sub-phenotypes and eventual risk of RRT highlighting potential therapeutic targets. Urine proteomics may be used to non-invasively classify SP2 participants.","journal":"Critical Care","year":2024,"id":427198,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8896,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":305235,"name":"Eric D. Morrell","orcid":"0000-0001-9900-3604","position":1,"is_corresponding":false},{"id":493556,"name":"F. Linzee Mabrey","orcid":"0000-0003-0263-9601","position":2,"is_corresponding":false},{"id":684993,"name":"Neha A. Sathe","orcid":"0000-0002-9072-0559","position":3,"is_corresponding":false},{"id":1126748,"name":"Zoie A. Bailey","orcid":null,"position":4,"is_corresponding":false},{"id":806018,"name":"Sarah Speckmaier","orcid":null,"position":5,"is_corresponding":false},{"id":1126310,"name":"J.L. Lo","orcid":"0000-0002-6164-7065","position":6,"is_corresponding":false},{"id":255634,"name":"Leila R. Zelnick","orcid":"0000-0002-8461-5111","position":7,"is_corresponding":false},{"id":54241,"name":"Jonathan Himmelfarb","orcid":"0000-0002-3319-1224","position":8,"is_corresponding":false},{"id":305239,"name":"Carmen Mikacenic","orcid":"0000-0001-8966-5161","position":9,"is_corresponding":false},{"id":15403,"name":"Laura Evans","orcid":"0000-0002-3176-6493","position":10,"is_corresponding":false},{"id":253256,"name":"Mark M. Wurfel","orcid":null,"position":11,"is_corresponding":false},{"id":249666,"name":"Pavan K. Bhatraju","orcid":"0000-0002-2606-4366","position":12,"is_corresponding":false},{"id":279183,"name":"Ian B. Stanaway","orcid":"0000-0002-0783-0918","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:58:47.805440Z","pmid":"39695715","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":[]}