TF, TFPI and Plasmin as Novel Bio-markers in Early Diagnosis of Lupus Nephritis

Urinary Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI) and Plasmin as Bio-markers in Early Diagnosis of Lupus Nephritis

Sponsors

Lead Sponsor: Assiut University

Source Assiut University
Brief Summary

Urinary levels of plasmin ,TF , and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti ds DNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-ds DNA and complement C3

Detailed Description

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affects various organs, characterized by diverse autoantibodies production,mainly anti-DNA and anti-nuclear antibodies . It demonstrates variations in incidence,prevalence, disease activity and prognosis according to race and ethnicity . Lupus nephritis (LN) is one of the most frequent and severe clinical manifestations of SLE, it affects over 60% of SLE patients representing a leading cause of morbidity and mortality . Early diagnosis and monitoring of the disease flares are still challenging , although of the novel immunosuppressive drugs and biologics, which brought improvements in recent SLE/LN survival rates . The American College of Rheumatology (ACR) guidelines for the treatment of lupus nephritis , recommend change in treatment if response to therapy has not been achieved after 6 months of induction therapy. However, response to therapy is not well defined. In addition, renal damage can occur within 6 months while waiting to define this response. Decision support tools could help define response at the start of induction therapy and have the potential to improve outcomes . Use of laboratory parameters for LN such as creatinine clearance, anti-ds DNA, proteinuria, urine protein-to-creatinine ratio (U-PCR),and complement levels are undesirable. These markers are of less sensitivity and specificity for evolve renal activity and injury in LN.They are not directly correlated with kidney damage, which can arise before kidney function affection. Outbreak of nephritis may occur in any condition in absence and new rise in the level of proteinuria. Kidney biopsy is a gold standard to assess the histological category of LN and the level of activity and chronicity in glomeruli. But, it is an invasive procedure and continual biopsies are inappropriate in the observing and follow up of LN . It may have sampling error because of extent number of glomeruli obtained for LN activity and chronicity. So , many studies are focusing on identifying non-invasive biomarkers for the early diagnosis and follow up of the disease and the therapy response. Urine is easily collected and can reflect the underlying renal affection more accurately than serum. Therefore, urine bio-markers represent promising candidates for the early disease diagnosis and monitoring .Thus, novel urinary bio-markers, which are able to distinguish lupus kidney activity and its extremity, anticipate kidney outbreak, and observe treatment reciprocation and illness breakthrough are clearly obligatory . Urinary bio-markers are more sensitive for lupus nephritis;they can appear in urine before functional derangement . Coagulation system disorders and hyper-coagulability state have been reported in lupus nephritis, also the frequency of thrombotic events was documented to be higher in SLE patients than in the general population, and these events were associated with poor outcome .Both thrombo-genic and thrombolytic cascades appear to be up-regulated in lupus nephritis, with proteins from both cascades appearing in the urine . Urinary levels of plasmin ,TF and TFPI are all elevated in active LN patients compared to inactive LN patients and healthy controls. All four proteins correlated with systemic disease activity and renal disease activity. Importantly, urine plasmin performed best among the four proteins in discriminating active LN from inactive disease, even better than traditional markers, such as anti dsDNA and complement C3. Furthermore, the combination of urine plasmin and TFPI showed higher specificity and negative predictive values than urine plasmin when compared to anti-dsDNA and complement C3.

Overall Status Not yet recruiting
Start Date 2020-04-01
Completion Date 2023-12-01
Primary Completion Date 2023-04-01
Study Type Observational
Primary Outcome
Measure Time Frame
The diagnostic utility of tissue factor ,, tissue factor pathway inhibitor and plasmin as biomarkers for early detection of lupus nephritis (LN) 2023
the correlation of these bio-markers to the clinical staging , the disease activity index and revised treatment . 2023
Enrollment 100
Condition
Intervention

Intervention Type: Diagnostic Test

Intervention Name: Urinary tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasmin

Description: urinary sample

Eligibility

Sampling Method:

Probability Sample

Criteria:

Inclusion Criteria: 1. age >15 years 2. SLE patients fullfiling ACR diagnostic criteria Exclusion Criteria: 1. Renal artery stenosis, congenital renal diseases ,renal tumor,other causes of GN 2. Pregnancy. 3. coagulation disorders 4. DM,HTN and the other connective tissue disease 5. Obesity 6. CKD

Gender:

All

Minimum Age:

15 Years

Maximum Age:

60 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Contact

Last Name: Salwa Salah Elgendy, professor dr

Phone: 01005766155

Email: [email protected]

Verification Date

2020-01-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Assiut University

Investigator Full Name: Ayat salah

Investigator Title: principal investigator

Has Expanded Access No
Condition Browse
Arm Group

Label: SLE patients without lupus nephritis

Description: 40 SLE patients 40SLE patients( All SLE pt. satisfied the ACR criteria for SLE diagnosis) these patients will be without any evidences of nephritis

Label: SLE patients with lupus nephritis

Description: 40SLE patients with evidences of nephritis

Label: healthy control group

Description: 20 healthy subjects matched age and sex with be enrolled as healthy control group

Patient Data Undecided
Study Design Info

Observational Model: Case-Control

Time Perspective: Cross-Sectional

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