Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis
Abstract Objective This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). Methods Urine sa...
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-019-1959-y |
| _version_ | 1818097227997904896 |
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| author | Ling Qin Samantha Stanley Huihua Ding Ting Zhang Van Thi Thanh Truong Teja Celhar Anna-Marie Fairhurst Claudia Pedroza Michelle Petri Ramesh Saxena Chandra Mohan |
| author_facet | Ling Qin Samantha Stanley Huihua Ding Ting Zhang Van Thi Thanh Truong Teja Celhar Anna-Marie Fairhurst Claudia Pedroza Michelle Petri Ramesh Saxena Chandra Mohan |
| author_sort | Ling Qin |
| collection | DOAJ |
| description | Abstract Objective This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). Methods Urine samples from 113 biopsy-proven LN patients (89 active LN and 24 inactive LN), 45 chronic kidney disease patients, and 41 healthy controls were examined for d-dimer, plasmin, TF, and TFPI levels by ELISA. The area under the receiver operating characteristic curve (AUC) analysis, multivariate regression analysis, and Bayesian network analysis were performed to assess the diagnostic value of the assayed molecules in LN. Results Although urinary d-dimer, plasmin, TF, and TFPI were all elevated in active LN compared to all control groups, and correlated with rSLEDAI and SLICC RAS disease activity indices, urine plasmin emerged as the strongest independent predictor of eGFR and renal disease status, by multivariate regression analysis and Bayesian network analysis. Whereas urine plasmin discriminated active LN from inactive disease with an AUC of 0.84, the combination of urine plasmin and TFPI discriminated ALN from ILN with an AUC of 0.86, with both surpassing the specificity and positive predictive value of traditional markers such as anti-dsDNA and complement C3. Conclusion Both thrombogenic and thrombolytic cascades appear to be upregulated in lupus nephritis, with proteins from both cascades appearing in the urine. Of the coagulation cascade proteins surveyed, urine plasmin emerges as the strongest predictor of eGFR and clinical renal disease in patients with LN. |
| first_indexed | 2024-12-10T23:17:11Z |
| format | Article |
| id | doaj.art-044571c0897943c58b272ca0ea949956 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-10T23:17:11Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-044571c0897943c58b272ca0ea9499562022-12-22T01:29:49ZengBMCArthritis Research & Therapy1478-63622019-07-0121111010.1186/s13075-019-1959-yUrinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritisLing Qin0Samantha Stanley1Huihua Ding2Ting Zhang3Van Thi Thanh Truong4Teja Celhar5Anna-Marie Fairhurst6Claudia Pedroza7Michelle Petri8Ramesh Saxena9Chandra Mohan10Department of Nephrology & Rheumatology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Biomedical Engineering, University of HoustonDepartment of Biomedical Engineering, University of HoustonDepartment of Biomedical Engineering, University of HoustonDepartment of Pediatrics, UT HoustonSingapore Immunology Network, Agency for Science, Technology, and ResearchSingapore Immunology Network, Agency for Science, Technology, and ResearchDepartment of Pediatrics, UT HoustonDepartment of Rheumatology, John Hopkins Medical UniversityDepartment of Nephrology, UT Southwestern Medical CenterDepartment of Biomedical Engineering, University of HoustonAbstract Objective This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). Methods Urine samples from 113 biopsy-proven LN patients (89 active LN and 24 inactive LN), 45 chronic kidney disease patients, and 41 healthy controls were examined for d-dimer, plasmin, TF, and TFPI levels by ELISA. The area under the receiver operating characteristic curve (AUC) analysis, multivariate regression analysis, and Bayesian network analysis were performed to assess the diagnostic value of the assayed molecules in LN. Results Although urinary d-dimer, plasmin, TF, and TFPI were all elevated in active LN compared to all control groups, and correlated with rSLEDAI and SLICC RAS disease activity indices, urine plasmin emerged as the strongest independent predictor of eGFR and renal disease status, by multivariate regression analysis and Bayesian network analysis. Whereas urine plasmin discriminated active LN from inactive disease with an AUC of 0.84, the combination of urine plasmin and TFPI discriminated ALN from ILN with an AUC of 0.86, with both surpassing the specificity and positive predictive value of traditional markers such as anti-dsDNA and complement C3. Conclusion Both thrombogenic and thrombolytic cascades appear to be upregulated in lupus nephritis, with proteins from both cascades appearing in the urine. Of the coagulation cascade proteins surveyed, urine plasmin emerges as the strongest predictor of eGFR and clinical renal disease in patients with LN.http://link.springer.com/article/10.1186/s13075-019-1959-yLupus nephritisBiomarkersPlasminTissue factorTissue factor pathway inhibitorD-dimer |
| spellingShingle | Ling Qin Samantha Stanley Huihua Ding Ting Zhang Van Thi Thanh Truong Teja Celhar Anna-Marie Fairhurst Claudia Pedroza Michelle Petri Ramesh Saxena Chandra Mohan Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis Arthritis Research & Therapy Lupus nephritis Biomarkers Plasmin Tissue factor Tissue factor pathway inhibitor D-dimer |
| title | Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis |
| title_full | Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis |
| title_fullStr | Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis |
| title_full_unstemmed | Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis |
| title_short | Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis |
| title_sort | urinary pro thrombotic anti thrombotic and fibrinolytic molecules as biomarkers of lupus nephritis |
| topic | Lupus nephritis Biomarkers Plasmin Tissue factor Tissue factor pathway inhibitor D-dimer |
| url | http://link.springer.com/article/10.1186/s13075-019-1959-y |
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