Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis

Background Renal fibrosis, the terminal pathological pathway of chronic kidney disease (CKD), lacks reliable noninvasive biomarkers for clinical assessment. Current diagnostic reliance on renal biopsy—despite its gold-standard status—poses risks of bleeding and sampling errors, necessitating alterna...

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Main Authors: Ying Yu, Yang-yang Niu, Ying-ying Zhang, Chen Yu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2534493
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author Ying Yu
Yang-yang Niu
Ying-ying Zhang
Chen Yu
author_facet Ying Yu
Yang-yang Niu
Ying-ying Zhang
Chen Yu
author_sort Ying Yu
collection DOAJ
description Background Renal fibrosis, the terminal pathological pathway of chronic kidney disease (CKD), lacks reliable noninvasive biomarkers for clinical assessment. Current diagnostic reliance on renal biopsy—despite its gold-standard status—poses risks of bleeding and sampling errors, necessitating alternatives. Long non-coding RNA growth arrest-specific 5 (GAS5) regulates fibrogenic pathways, but its utility as a liquid biopsy marker remains unexplored.Method This prospective cross-sectional study quantified GAS5 levels in paired plasma and urine samples from 198 CKD patients (stratified by renal fibrosis scoring: mild: <25%, moderate: 25–50%, severe: ≥50% fibrotic area) and 20 healthy controls. Multivariate regression models adjusted for cardiorenal confounders (hypertension, blood pressure, and so on) evaluated GAS5’s association with fibrosis.Results Plasma GAS5 levels increased with renal fibrosis severity, whereas urinary GAS5 exhibited progressive suppression. After adjusting for factors such as hypertension history, systolic and diastolic blood pressure, blood urea nitrogen, creatinine, eGFR, and uric acid, use of ACEI/ARB, multivariate analysis showed significant associations between urinary GAS5 level and renal fibrosis. ROC analysis revealed urinary GAS5’s superior diagnostic accuracy compared with eGFR and TGF-β1. AUCs of urinary GAS5 were even higher in moderate and severe renal fibrosis group.Conclusions While plasma GAS5 upregulation and urinary GAS5 suppression reflect inverse expression patterns in renal fibrosis, urinary GAS5 emerges as the dominant noninvasive biomarker due to its superior diagnostic performance (AUC = 0.868) and clinical accessibility.
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spelling doaj-art-ff21976d187048a3b9e4f743d6f3f6c82025-07-21T03:27:20ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2534493Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosisYing Yu0Yang-yang Niu1Ying-ying Zhang2Chen Yu3Department of Nephrology, School of Medicine, Tongji Hospital, Tongji University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Tongji Hospital, Tongji University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Tongji Hospital, Tongji University, Shanghai, ChinaDepartment of Nephrology, School of Medicine, Tongji Hospital, Tongji University, Shanghai, ChinaBackground Renal fibrosis, the terminal pathological pathway of chronic kidney disease (CKD), lacks reliable noninvasive biomarkers for clinical assessment. Current diagnostic reliance on renal biopsy—despite its gold-standard status—poses risks of bleeding and sampling errors, necessitating alternatives. Long non-coding RNA growth arrest-specific 5 (GAS5) regulates fibrogenic pathways, but its utility as a liquid biopsy marker remains unexplored.Method This prospective cross-sectional study quantified GAS5 levels in paired plasma and urine samples from 198 CKD patients (stratified by renal fibrosis scoring: mild: <25%, moderate: 25–50%, severe: ≥50% fibrotic area) and 20 healthy controls. Multivariate regression models adjusted for cardiorenal confounders (hypertension, blood pressure, and so on) evaluated GAS5’s association with fibrosis.Results Plasma GAS5 levels increased with renal fibrosis severity, whereas urinary GAS5 exhibited progressive suppression. After adjusting for factors such as hypertension history, systolic and diastolic blood pressure, blood urea nitrogen, creatinine, eGFR, and uric acid, use of ACEI/ARB, multivariate analysis showed significant associations between urinary GAS5 level and renal fibrosis. ROC analysis revealed urinary GAS5’s superior diagnostic accuracy compared with eGFR and TGF-β1. AUCs of urinary GAS5 were even higher in moderate and severe renal fibrosis group.Conclusions While plasma GAS5 upregulation and urinary GAS5 suppression reflect inverse expression patterns in renal fibrosis, urinary GAS5 emerges as the dominant noninvasive biomarker due to its superior diagnostic performance (AUC = 0.868) and clinical accessibility.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2534493GAS5biomarkerrenal fibrosisserumurine
spellingShingle Ying Yu
Yang-yang Niu
Ying-ying Zhang
Chen Yu
Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
Renal Failure
GAS5
biomarker
renal fibrosis
serum
urine
title Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
title_full Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
title_fullStr Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
title_full_unstemmed Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
title_short Urinary long non-coding RNA GAS5 as a noninvasive diagnostic biomarker for renal fibrosis
title_sort urinary long non coding rna gas5 as a noninvasive diagnostic biomarker for renal fibrosis
topic GAS5
biomarker
renal fibrosis
serum
urine
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2534493
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AT yingyingzhang urinarylongnoncodingrnagas5asanoninvasivediagnosticbiomarkerforrenalfibrosis
AT chenyu urinarylongnoncodingrnagas5asanoninvasivediagnosticbiomarkerforrenalfibrosis