Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis

Ling Qin, Samantha Stanley, Huihua Ding, Ting Zhang, Van Truong, Teja Celhar, Anna Marie Fairhurst, Claudia Pedroza, Michelle Petri, Ramesh Saxena, Chandra Mohan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Number of pages1
JournalArthritis research & therapy
Volume21
Issue number1
DOIs
StatePublished - Jul 18 2019

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Lupus Nephritis
Fibrinolysin
Biomarkers
Urine
Thromboplastin
Area Under Curve
Bayes Theorem
Multivariate Analysis
Regression Analysis
Kidney
Complement C3
Chronic Renal Insufficiency
ROC Curve
Proteins
Enzyme-Linked Immunosorbent Assay
Biopsy
Control Groups
lipoprotein-associated coagulation inhibitor

Keywords

  • Biomarkers
  • D-dimer
  • Lupus nephritis
  • Plasmin
  • Tissue factor
  • Tissue factor pathway inhibitor

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis. / Qin, Ling; Stanley, Samantha; Ding, Huihua; Zhang, Ting; Truong, Van; Celhar, Teja; Fairhurst, Anna Marie; Pedroza, Claudia; Petri, Michelle; Saxena, Ramesh; Mohan, Chandra.

In: Arthritis research & therapy, Vol. 21, No. 1, 18.07.2019.

Research output: Contribution to journalArticle

Qin, L, Stanley, S, Ding, H, Zhang, T, Truong, V, Celhar, T, Fairhurst, AM, Pedroza, C, Petri, M, Saxena, R & Mohan, C 2019, 'Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis', Arthritis research & therapy, vol. 21, no. 1. https://doi.org/10.1186/s13075-019-1959-y
Qin, Ling ; Stanley, Samantha ; Ding, Huihua ; Zhang, Ting ; Truong, Van ; Celhar, Teja ; Fairhurst, Anna Marie ; Pedroza, Claudia ; Petri, Michelle ; Saxena, Ramesh ; Mohan, Chandra. / Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis. In: Arthritis research & therapy. 2019 ; Vol. 21, No. 1.
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AU - Qin, Ling

AU - Stanley, Samantha

AU - Ding, Huihua

AU - Zhang, Ting

AU - Truong, Van

AU - Celhar, Teja

AU - Fairhurst, Anna Marie

AU - Pedroza, Claudia

AU - Petri, Michelle

AU - Saxena, Ramesh

AU - Mohan, Chandra

PY - 2019/7/18

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N2 - 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.

AB - 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.

KW - Biomarkers

KW - D-dimer

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KW - Plasmin

KW - Tissue factor

KW - Tissue factor pathway inhibitor

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