Monitoring Lupus Nephritis Through Urinary Extracellular Vesicles

September 2, 2025 updated by: Kolding Sygehus

Monitoring and Detecting Lupus Nephritis Through Urinary Extracellular Vesicles in Urine

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that can lead to irreversible kidney damage if not detected and managed promptly. LN is classified and treated based on its histopathological features obtained by invasive kidney biopsy. Recent research has suggested urinary extracellular vesicles (uEVs) as potential non-invasive biomarkers. The primary objective of this prospective study is to investigate the utility of uEVs in LN.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that can lead to irreversible kidney damage if not detected and managed promptly. LN is classified based on its histopathological features. The classification helps in determining the severity and appropriate treatment strategies for the condition and to rule out other conditions that may mimic the clinical picture of LN. The classification system most commonly used is the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which divides lupus nephritis into six classes: I) Minimal Change, II) Mesangial Proliferative LN, III) Focal Proliferative LN, IV) Diffus proliferative LN, V) Membranous LN, VI) Advanced Sclerosing LN. The classification requires invasive kidney biopsies, which are hardly accessible and associated with potential complications and patient discomfort. Furthermore the kidney biopsy only represent a small part of the kidney. Recent research has suggested urinary extracellular vesicles (uEVs) as potential non-invasive biomarkers for kidney diseases, including LN. uEVS are small nano-sized extracellular vesicles of endosomal origin, which are secreted into the urine through fusion of multivesicular bodies with the plasma membrane. Thus, they could represent a promising liquid biopsy that reflects the pattern and/or severity of renal injury.

Hypothesis: The primary objective of this prospective study is to investigate the utility of urinary exosomes as non-invasive biomarkers for monitoring the activity and progression of lupus nephritis.

Methods: SLE patients, fulfilling the 2019 EULAR/ACR classification criteria, referred to kidney biopsy, will be recruited from Department of Rheumatology and Department of Nephrology at Odense University Hospital. Detailed demographic and clinical data including age, sex, ethnicity, medicine, duration of SLE activity, SLE damage and laboratory results will be collected from each patient. Activity of SLE at the time of biopsy will be evaluated using SLE disease activity index 2000 (SLEDAI-2K). SLE damage will be evaluated in accordance with the SLICC damage index. Spot-urine samples will be collected, added protease-inhibitors and frozen at -80 degree. UEVs will be isolated using polyethylene glycol (PEG) precipitation, the concentration of uEV will be determined and protein accessed using western blotting and/or PCR. Glomerular specific uEVs will be isolated and previous developed tests will be applied to detect the membrane attack complex (MAC)/C5b-9 complex. uEVs from plasma/serum will be isolated to test for correlation with uEVs. Kidney biopsies will be histological analyzed at Department of Pathology by experienced nephropathologists according to existing clinical guidelines. Differences in uEV cargo between SLE patients with and without lupus nephritis will be analyzed using appropriate statistical tests. Correlations between uEV biomarkers, histological differences on the kidney biopsy and disease activity will be evaluated using Pearson's correlation analysis.

Perspective: This prospective study aims to establish urinary extracellular vesicles as potential non-invasive biomarkers for monitoring lupus nephritis in SLE patients. The findings from this research may lead to the development of more efficient and patient-friendly approaches for LN management, enabling timely interventions and improved renal outcomes in SLE patients.

Study Type

Observational

Enrollment (Estimated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Kolding, Denmark
        • Not yet recruiting
        • Kolding Hospital
        • Contact:
      • Odense, Denmark, 5000
        • Not yet recruiting
        • Department of Nephrology
        • Contact:
          • michael Aarup, MD, consultant
      • Odense, Denmark, 5000
      • Odense, Denmark, 5230
        • Not yet recruiting
        • Univesity of Southern Denmark
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Patients known with SLE with and without kidney involvement, a biopsy control and a group of healthy controls.

Description

SLE patients with kidney involvement

Inclusion criteria:

  • > 18 years old
  • Fulfilling the 2019 EULAR/ACR classification criteria
  • Positive autoantibodies, medical history and obejctive examination compatible with SLE
  • Referred to kidney biopsy

Exclusion criteria:

  • Lack of ability or willingness to provide informed consent
  • Significant comorbidity, which is considered to potentially impact the outcome

SLE patients with no sign of kidney disease

Inclusion criteria:

  • > 18 years old
  • Fulfilling the 2019 EULAR/ACR classification criteria
  • Positive autoantibodies, medical history and obejctive examination compatible with SLE
  • Normal plasma creatinine
  • Urine albumine/creatinine < 100 mg/g

Exclusion criteria:

  • Lack of ability or willingness to provide informed consent
  • Significant comorbidity, which is considered to potentially impact the outcome

Healthy controls:

Inclusion criteria:

  • > 18 years old
  • No known kidney disease

Exclusion criteria:

  • Lack of ability or willingness to provide informed consent
  • Urine albumin-creatinine ratio > 100 mg/g or proteinuria > 100 mg/day
  • Postive autoantibodies
  • Significant comorbidity, which is considered to potentially impact the outcome

Biopsy control:

Inclusion criteria:

  • > 18 years old
  • Negative autoantibiodies and immunoglobulines
  • Referred to kidney biopsy

Exclusion criteria:

  • Lack of ability or willingness to provide informed consent
  • Significant comorbidity, which is considered to potentially impact the outcome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Healthy controls
Diagnostic test: Urinary extracellular vesicle testing
Urinary extracellular vesicles will be isolated and tested for complement activation and other markers of kidney disease
Systemic lupus erythomatosus with lupus nephritis
SLE patients with kidney involvement
Diagnostic test: Kidney biopsy
Patient refered to kidney biopsy independent of the presented study
Other Names:
  • No expected complement activation
Diagnostic test: Urinary extracellular vesicle testing
Urinary extracellular vesicles will be isolated and tested for complement activation and other markers of kidney disease
Diagnostic test: Autoimmunity in plasma
Expected autoimmunity in plasma isolated from blood samples
Systemic lupus erythomatosus without lupus nephritis
SLE patients, fulfilling the 2019 EULAR/ACR classification criteria with no sign of kidney disease
Diagnostic test: Urinary extracellular vesicle testing
Urinary extracellular vesicles will be isolated and tested for complement activation and other markers of kidney disease
Diagnostic test: Autoimmunity in plasma
Expected autoimmunity in plasma isolated from blood samples
Biopsy controls
A biopsy control group with no predictive complement activation referred to biopsy
Diagnostic test: Kidney biopsy
Patient refered to kidney biopsy independent of the presented study
Other Names:
  • No expected complement activation
Diagnostic test: Urinary extracellular vesicle testing
Urinary extracellular vesicles will be isolated and tested for complement activation and other markers of kidney disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between kidney biopsy and urinay extracellular vesicles
Time Frame: Urinary extracellular vesicles will be isolated from urine collected at the day of kidney biopsy/baseline. Analysis will be performed when all samples are collected. Estimated after 5 years.
The primary outcome is to investigate the correlation between histological findings from kidney biopsy and urinary extracelluar vesicles, with the aim of assessing whether there is concordance between the two methods in relation to disease severity and classification.
Urinary extracellular vesicles will be isolated from urine collected at the day of kidney biopsy/baseline. Analysis will be performed when all samples are collected. Estimated after 5 years.
Complement activation in urinary extracellular vesicles
Time Frame: Measured on urinary extracellular vesicles obtained at the day of biopsy/baseline. Analysis will be performed when all samples are collected, estimated after 5 years.
Urinary extracellular vesicles will be isolated. Complement activation will be detected using an in-house ELISA assay
Measured on urinary extracellular vesicles obtained at the day of biopsy/baseline. Analysis will be performed when all samples are collected, estimated after 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between urinary extracellular vesicles and extracellular vesicles from plasma
Time Frame: Blood- og and urine samples will be collected at the day of kidney biopsy/baseline. Analysis will be performed when all samples are collecting, estimated after 5 years.
A seconday outcome is to invesigate the correlation between urinary extracellular vesicles and extracellular vesicles from plasma, to see if the same results could be obtained in plasma samples
Blood- og and urine samples will be collected at the day of kidney biopsy/baseline. Analysis will be performed when all samples are collecting, estimated after 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kolding Sygehus

Collaborators

Odense University Hospital
University of Southern Denmark

Investigators

  • Study Chair: Anne F Christensen, Chief of Medicine, MD, phd, Sygehus Lillebaelt, Kolding Hospitl

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2024

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2030

Study Registration Dates

First Submitted

October 11, 2024

First Submitted That Met QC Criteria

October 11, 2024

First Posted (Actual)

October 15, 2024

Study Record Updates

Last Update Posted (Estimated)

September 9, 2025

Last Update Submitted That Met QC Criteria

September 2, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SLELNuEV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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