Functionally Essential Tubular Proteins Are Lost to Urine-Excreted, Large Extracellular Vesicles during Chronic Renal Insufficiency.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34263177", "kind": "science-record", "revision": 2, "content_hash": "sha256:14e9e3ff2bebf89ed725dca6a04ec926b7d2170a4ab71aa53e2b353ecf71386e", "created_at": "2026-11-01T17:35:40Z", "updated_at": "2026-11-01T18:56:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Functionally Essential Tubular Proteins Are Lost to Urine-Excreted, Large Extracellular Vesicles during Chronic Renal Insufficiency.", "doi": "10.34067/kid.0001212020", "pmid": "34263177", "authors": ["Ryan J Adam", "Mark R Paterson", "Lukus Wardecke", "Brian R Hoffmann", "Alison J Kriegel"], "journal": "Kidney360", "year": 2020, "abstract": "BACKGROUND: The 5/6 nephrectomy (5/6Nx) rat model recapitulates many elements of human CKD. Within weeks of surgery, 5/6Nx rats spontaneously exhibit proximal tubular damage, including the production of very large extracellular vesicles and brush border shedding. We hypothesized that production and elimination of these structures, termed large renal tubular extracellular vesicles (LRT-EVs), into the urine represents a pathologic mechanism by which essential tubule proteins are lost.\nMETHODS: LRT-EVs were isolated from 5/6Nx rat urine 10 weeks after surgery. LRT-EV diameters were measured. LRT-EV proteomic analysis was performed by tandem mass spectrometry. Data are available via the ProteomeXchange Consortium with identifier PXD019207. Kidney tissue pathology was evaluated by trichrome staining, TUNEL staining, and immunohistochemistry.\nRESULTS: LRT-EV size and a lack of TUNEL staining in 5/6Nx rats suggest LRT-EVs to be distinct from exosomes, microvesicles, and apoptotic bodies. LRT-EVs contained many proximal tubule proteins that, upon disruption, are known to contribute to CKD pathologic hallmarks. Select proteins included aquaporin 1, 16 members of the solute carrier family, basolateral Na+/K+-ATPase subunit ATP1A1, megalin, cubilin, and sodium-glucose cotransporters (SLC5A1 and SLC5A2). Histologic analysis confirmed the presence of apical membrane proteins in LRT-EVs and brush border loss in 5/6Nx rats.\nCONCLUSIONS: This study provides comprehensive proteomic analysis of a previously unreported category of extracellular vesicles associated with chronic renal stress. Because LRT-EVs contain proteins responsible for essential renal functions known to be compromised in CKD, their formation and excretion may represent an underappreciated pathogenic mechanism.", "claims": [{"id": "claim-data-access", "statement": "Data are available via the ProteomeXchange Consortium with identifier PXD019207.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34263177", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Data are available via the ProteomeXchange Consortium with identifier PXD019207."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study provides comprehensive proteomic analysis of a previously unreported category of extracellular vesicles associated with chronic renal stress.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34263177", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study provides comprehensive proteomic analysis of a previously unreported category of extracellular vesicles associated with chronic renal stress."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study provides comprehensive proteomic analysis of a previously unreported category of extracellular vesicles associated with chronic renal stress.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34263177"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Within weeks of surgery, 5/6Nx rats spontaneously exhibit proximal tubular damag", "t. METHODS: LRT-EVs were isolated from 5/6Nx rat urine 10 weeks after surgery. LRT-EV diamete", "V size and a lack of TUNEL staining in 5/6Nx rats suggest LRT-EVs to be distinct from exosomes"], "order_basis": "paper_text_order:133", "id": "assay:1"}, {"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["V proteomic analysis was performed by tandem mass spectrometry. Data are available via the ProteomeXchange", "gery. LRT-EV diameters were measured. 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