Discovery of Fibrinogen γ-chain as a potential urinary biomarker for renal interstitial fibrosis in IgA nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36941570", "kind": "science-record", "revision": 3, "content_hash": "sha256:f9f8601a5cc211d543b0b08dd53f5143528622d0772702d395b6ccdbcf02cdbc", "created_at": "2026-11-01T19:01:35Z", "updated_at": "2026-11-01T22:09:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Discovery of Fibrinogen γ-chain as a potential urinary biomarker for renal interstitial fibrosis in IgA nephropathy.", "doi": "10.1186/s12882-023-03103-7", "pmid": "36941570", "authors": ["Jie Guan", "Meiling Wang", "Man Zhao", "Wentao Ni", "Man Zhang"], "journal": "BMC nephrology", "year": 2023, "abstract": "BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD). Renal interstitial fibrosis is a hallmark of CKD progression. Non-invasive biomarkers are needed to dynamically evaluate renal fibrosis. Data independent acquisition (DIA)-based liquid chromatography-mass spectrometry (DIA-MS) was used to identify candidate urinary biomarkers in IgAN patients with different renal interstitial fibrosis degrees.\nMETHODS: Eighteen biopsy-proven IgAN patients and six healthy controls were recruited in a discovery cohort. Interstitial fibrosis changes were evaluated according to Oxford MEST-C scores. Urinary samples were analyzed with DIA-MS to identify hub proteins. Hub proteins were then confirmed by enzyme-linked immunosorbent assay (ELISA) in a validation cohort and the associated gene mRNA expression was analyzed using public gene expression omnibus (GEO) datasets.\nRESULTS: Complement and coagulation cascades pathway was the main KEGG pathway related to the over-expressed proteins. Fibrinogen γ-Chain (FGG) was selected as the potential urinary marker for further validation. Urinary FGG to creatinine ratio (uFGG/Cr) levels were higher in both disease controls and IgAN group than in healthy controls, but were not significantly different between IgAN and disease groups. uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group. In disease control group, uFGG/Cr was higher in patients with T1 + 2 compared to those with T0. uFGG/Cr had a good discriminatory power to distinguish different fibrosis stages in IgAN: interstitial fibrosis ≤ 5% (minimal fibrosis) vs. interstitial fibrosis (mild fibrosis) > 5%, AUC 0.743; T0 vs. T1 + 2, AUC 0.839; T0 + 1 vs. T2, AUC 0.854. In disease control group, uFGG/Cr showed better performance of AUC than UTP between minimal and mild fibrosis (p = 0.038 for Delong's test). Moreover, GSE104954 dataset showed that FGG mRNA expression was up-regulated (fold change 1.20, p = 0.009) in tubulointerstitium of IgAN patients when compared to healthy living kidney donors.\nCONCLUSION: Urinary FGG is associated with renal interstitial fibrosis and could be used as a noninvasive biomarker for renal fibrosis in IgAN.", "claims": [{"id": "claim-method", "statement": "Random urine samples were collected on the same day of renal biopsy and centrifuged (400×g, 5min) to remove cellular debris within 4 hours of collection. Spearman’s correlation analysis was performed among different variables in IgAN group with SPSS software (version 19.0). Receiver operating characteristics curves (ROC) was determined by SPSS software, with the area under the curve (AUC) compared using the paired DeLong’s test by MedCalc software (version 18.2.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36941570", "locator": "sections[6] \"Urine sample collection and preparation\" paragraph 2", "quote": "Random urine samples were collected on the same day of renal biopsy and centrifuged (400×g, 5min) to remove cellular debris within 4 hours of collection."}, {"asset": "source:pmid:36941570", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Spearman’s correlation analysis was performed among different variables in IgAN group with SPSS software (version 19.0)."}, {"asset": "source:pmid:36941570", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Receiver operating characteristics curves (ROC) was determined by SPSS software, with the area under the curve (AUC) compared using the paired DeLong’s test by MedCalc software (version 18.2.1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available dataset was analyzed in this study and these data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE104954. The experimental data used and analyzed in the current study were available from the supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36941570", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "Publicly available dataset was analyzed in this study and these data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE104954. The experimental data used and analyzed in the current study were available from the supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group.", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group."}, "evidence": [{"asset": "source:pmid:36941570", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "uFGG/Cr was confirmed to be increased with the extent of renal fibrosis and presented moderate correlations with T score (r = 0.614, p < 0.01) and eGFR (r = -0.682, p < 0.01), and a mild correlation with UTP (r = 0.497, p < 0.01) in IgAN group.", "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:36941570"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104954"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104954"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36941570", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12882-023-03103-7", "sha256": "sha256:70314184f45ae57061eea9190d59b0dc6894bdec90538d41d1f5fb77792856f6", "bytes": 41173, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12882-023-03103-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10029243", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE104954", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104954", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE104954", "version": null, "note": "Publicly available dataset was analyzed in this study and these data can be found here: https://www.ncbi.nlm.nih.gov/geo/, GSE104954. 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Spearman’s correlation analysis was performed among different variables in IgAN group with SPSS software (version 19.0). Receiver operating characteristics curves (ROC) was determined by SPSS software, with the area under the curve (AUC) compared using the paired DeLong’s test by MedCalc software (version 18.2.1)."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "bootstrap_mean_difference", "expected_value": 0.01, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. 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