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

NCT ID: NCT04218890

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-01
• Study Completion Date: 2023-12-01

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.

Conditions

Lupus Nephritis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

SLE patients without lupus nephritis

40 SLE patients

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

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

Intervention Type: DIAGNOSTIC_TEST

urinary sample

SLE patients with lupus nephritis

40SLE patients with evidences of nephritis

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

Intervention Type: DIAGNOSTIC_TEST

urinary sample

healthy control group

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

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

Intervention Type: DIAGNOSTIC_TEST

urinary sample

Interventions

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

urinary sample

Intervention Type: DIAGNOSTIC_TEST

Eligibility 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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Ayat salah

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Salwa Salah Elgendy, professor dr

Role: CONTACT

salwaelgendi@yahoo.com

01005766155

Effat Abdelhady Eltony

Role: CONTACT

effattony@aun.edu.eg

01097330309

References

Qin L, Stanley S, Ding H, Zhang T, Truong VTT, Celhar T, Fairhurst AM, Pedroza C, Petri M, Saxena R, Mohan C. Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis. Arthritis Res Ther. 2019 Jul 18;21(1):176. doi: 10.1186/s13075-019-1959-y.

Reference Type: BACKGROUND

PMID: 31319876 (View on PubMed)

Frijns R, Fijnheer R, Schiel A, Donders R, Sixma J, Derksen R. Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers. J Rheumatol. 2001 Mar;28(3):514-9.

Reference Type: BACKGROUND

PMID: 11296951 (View on PubMed)

Ding H, Kharboutli M, Saxena R, Wu T. Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis. Clin Exp Immunol. 2016 Apr;184(1):11-8. doi: 10.1111/cei.12743. Epub 2016 Jan 11.

Reference Type: BACKGROUND

PMID: 26616478 (View on PubMed)

Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, Hanly JG, Isenberg DA, Nived O, Sturfelt G, van Vollenhoven R, Wallace DJ, Alarcon GS, Adu D, Avila-Casado C, Bernatsky SR, Bruce IN, Clarke AE, Contreras G, Fine DM, Gladman DD, Gordon C, Kalunian KC, Madaio MP, Rovin BH, Sanchez-Guerrero J, Steinsson K, Aranow C, Balow JE, Buyon JP, Ginzler EM, Khamashta MA, Urowitz MB, Dooley MA, Merrill JT, Ramsey-Goldman R, Font J, Tumlin J, Stoll T, Zoma A; Systemic Lupus International Collaborating Clinics. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum. 2008 Jun;58(6):1784-8. doi: 10.1002/art.23456.

Reference Type: BACKGROUND

PMID: 18512819 (View on PubMed)

Other Identifiers

ASA2

Identifier Type: -

Identifier Source: org_study_id