Biomarker Development for Autoimmune Disorders Involving the Kidneys (SILENT_LN)

SILENT-LN is a prospective observational cohort study of adults with systemic lupus erythematosus, including participants with no renal involvement, suspected renal involvement, active lupus nephritis, previous lupus nephritis, or inactive lupus nephritis. The study will measure pre-specified blood and urine biomarkers longitudinally during routine clinical care.

The study will evaluate whether blood and urine biomarker concentrations and biomarker panel scores are associated with active lupus nephritis, incident lupus nephritis, renal flare, treatment response, remission or inactive renal disease, kidney biopsy findings, and long-term renal outcomes.

Participants will provide blood and urine samples during routine clinical follow-up visits and at visits where renal involvement is clinically suspected. Clinical data, standard laboratory tests, disease activity assessments, kidney function measures, treatment information, and kidney biopsy findings, when available, will be recorded.

A predefined increase or persistent elevation in blood or urine biomarker levels will trigger a structured renal assessment, and kidney biopsy or re-biopsy may be performed if the integrated clinical assessment indicates suspected renal involvement, renal flare, or uncertainty regarding renal inflammatory activity and the procedure is considered safe and clinically appropriate.

The study is currently conducted at Oslo University Hospital, Riks Hospital and may expand to additional centers following funding and regulatory approvals.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis
• Intervention / Treatment: Diagnostic test: Longitudinal Blood and Urine Biomarker Monitoring

Detailed Description

SILENT-LN is a prospective observational longitudinal biomarker study in adults with systemic lupus erythematosus receiving routine clinical care. The study includes participants with and without renal involvement at enrollment. Participants will be followed for up to 5 years with serial collection of blood samples, urine samples, standard clinical data, routine laboratory data, treatment information, and kidney biopsy findings when clinically available.

The study includes the following pre-specified analysis populations:

Participants with systemic lupus erythematosus without lupus nephritis at enrollment, followed for incident or new-onset lupus nephritis.

Participants with suspected renal involvement or active lupus nephritis, evaluated for association between biomarker levels and active renal disease.

Participants with established or newly diagnosed lupus nephritis, followed longitudinally for renal flare, treatment response, remission or inactive renal disease, and long-term renal outcomes.

Participants undergoing biomarker-triggered renal assessment, in whom kidney biopsy or re-biopsy may be performed when biomarker elevation is accompanied by suspected renal involvement, possible renal flare, unresolved uncertainty regarding renal inflammatory activity, or discordance between biomarker findings and conventional clinical measures, provided that biopsy is considered safe and appropriate by the treating specialist.

Blood and urine biomarker concentrations will be measured using pre-specified laboratory assays. Biomarker results may be analyzed as individual biomarker concentrations and as pre-specified biomarker panel scores. When blood and urine biomarkers are combined, they will be aggregated into a pre-specified composite score according to the statistical analysis plan.

Active lupus nephritis, incident lupus nephritis, renal flare, treatment response, remission, and inactive renal disease will be defined according to predefined protocol criteria based on routine clinical assessment, urinalysis, proteinuria, kidney function, serological markers, disease activity assessment, treatment status, and kidney biopsy findings when available.

The study includes a biomarker-triggered renal assessment pathway. A predefined increase or persistent elevation in one or more blood or urine biomarkers will prompt a structured medical assessment for possible renal involvement or renal inflammatory activity. This assessment will integrate biomarker results with conventional clinical and laboratory information, including symptoms, urinalysis, proteinuria, urinary sediment, serum creatinine, estimated glomerular filtration rate, complement levels, anti-dsDNA antibodies, SLE disease activity, medication exposure, and treating physician assessment.

Kidney biopsy or re-biopsy may be performed when the integrated assessment indicates suspected lupus nephritis, possible renal flare, unresolved uncertainty regarding renal inflammatory activity, or discordance between biomarker findings and conventional clinical measures. Biopsy or re-biopsy will only be performed if the treating specialist considers the procedure safe and appropriate and the participant agrees to the procedure. Biomarker elevation alone will trigger medical assessment but will not automatically mandate biopsy.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Simin Jamaly, PhD; Phone Number: +4746949074; Email: simjam@ous-hf.no

Study Locations

• Norway
  • Oslo
    • Oslo, Oslo, Norway, 0372
      • Recruiting
      • Oslo universitetssykehus HF, Rikshospitalet, Clinic for Surgery and Specialized Medicine, Department of Rheumatology, Skin and Infectious Diseases
      • Contact: Simin Jamaly, PhD; Phone Number: +4746949074; Email: simjam@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adults with systemic lupus erythematosus receiving routine clinical care at Oslo University Hospital or another participating center. Participants may have no renal involvement, suspected renal involvement, active lupus nephritis, previous lupus nephritis, newly diagnosed lupus nephritis, inactive lupus nephritis, or lupus nephritis in remission. Participants will be recruited from the NOSVAR cohort and associated rheumatology outpatient clinics. The cohort will be followed prospectively with longitudinal collection of clinical data, standard laboratory data, treatment information, blood samples, urine samples, and kidney biopsy findings when clinically available.

Description

Inclusion Criteria:

• Age 18 years or older
• Established diagnosis of systemic lupus erythematosus according to accepted classification criteria
• Receiving routine clinical care at Oslo University Hospital or another participating center
• Able to provide informed consent according to the approved consent procedure
• Willing and able to provide blood and/or urine samples for biomarker analysis
• For the biopsy-validation analysis population: predefined increase or persistent elevation in one or more blood or urine biomarkers prompting structured renal assessment, with integrated medical assessment indicating suspected renal involvement, possible renal flare, unresolved uncertainty regarding renal inflammatory activity, or discordance between biomarker findings and conventional clinical measures

Exclusion Criteria:

• Inability to provide valid informed consent, unless an approved alternative consent procedure applies
• Known kidney disease not related to systemic lupus erythematosus that would prevent interpretation of lupus nephritis-related biomarker findings
• Previous kidney transplantation
• Active infection or acute medical instability that would interfere with study procedures or interpretation of biomarker findings in the time of sampling
• For the biopsy-validation analysis population: kidney biopsy or re-biopsy is considered unsafe or inappropriate by the treating specialist
• For the biopsy-validation analysis population: contraindication to native kidney biopsy according to local hospital procedures or specialist assessment
• For the biopsy-validation analysis population: participant declines kidney biopsy, re-biopsy, or participation in the biopsy-validation component

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults With Systemic Lupus Erythematosus; Adults with systemic lupus erythematosus receiving routine clinical care at Oslo University Hospital or another participating center. Participants may have no renal involvement, suspected renal involvement, active lupus nephritis, previous lupus nephritis, newly diagnosed lupus nephritis, inactive lupus nephritis, or lupus nephritis in remission. Participants will be followed prospectively with longitudinal blood and urine sampling, clinical assessment, standard laboratory testing, treatment data collection, and recording of kidney biopsy findings when clinically available.

Diagnostic test: Longitudinal Blood and Urine Biomarker Monitoring; All enrolled adults with systemic lupus erythematosus, with or without renal involvement, will undergo serial blood and urine biomarker monitoring during routine follow-up. Biomarker concentrations and panel scores will be analyzed in relation to renal disease status, including incident lupus nephritis, active or inactive lupus nephritis, renal flare, treatment response, remission, biopsy findings, and renal outcomes. Biomarker increase or persistent elevation may trigger structured renal assessment. Kidney biopsy or re-biopsy may be considered after integrated medical assessment if lupus nephritis activity is suspected or uncertain and the procedure is safe, appropriate, and accepted by the participant. Treatment decisions remain under the responsibility of the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Receiver Operating Characteristic Curve of the Combined Blood-and-Urine Biomarker Score for Active Lupus Nephritis	Area under the receiver operating characteristic curve, AUC, of the pre-specified combined blood-and-urine biomarker score for distinguishing active lupus nephritis from inactive lupus nephritis or systemic lupus erythematosus without renal involvement. The combined biomarker score will be calculated from pre-specified blood and urine biomarker concentrations according to the statistical analysis plan. Active lupus nephritis status will be defined according to predefined clinical criteria and kidney biopsy findings when available. The AUC will be reported as a unitless value with 95% confidence interval.	From enrollment through study completion, assessed up to 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Receiver Operating Characteristic Curve of the Urinary Biomarker Score for Active Lupus Nephritis	AUC of a pre-specified urinary biomarker score for distinguishing active lupus nephritis from inactive lupus nephritis or systemic lupus erythematosus without renal involvement. The urinary biomarker score will be calculated from pre-specified urine biomarker concentrations according to the statistical analysis plan. The AUC will be reported as a unitless value with 95% confidence interval.	From enrollment through study completion, assessed up to 5 years.
Area Under the Receiver Operating Characteristic Curve of the Blood Biomarker Score for Active Lupus Nephritis	AUC of a pre-specified blood biomarker score for distinguishing active lupus nephritis from inactive lupus nephritis or systemic lupus erythematosus without renal involvement. The blood biomarker score will be calculated from pre-specified blood biomarker concentrations according to the statistical analysis plan. The AUC will be reported as a unitless value with 95% confidence interval.	From enrollment through study completion, assessed up to 5 years.
Sensitivity of the Combined Blood-and-Urine Biomarker Score Cut-Off for Active Lupus Nephritis	Sensitivity of the pre-specified combined blood-and-urine biomarker score cut-off for identifying active lupus nephritis. Sensitivity will be reported as the percentage of participants with active lupus nephritis who have a biomarker score above the pre-specified cut-off.	From enrollment through study completion, assessed up to 5 years.
Specificity of the Combined Blood-and-Urine Biomarker Score Cut-Off for Active Lupus Nephritis	Specificity of the pre-specified combined blood-and-urine biomarker score cut-off for identifying active lupus nephritis. Specificity will be reported as the percentage of participants without active lupus nephritis who have a biomarker score below the pre-specified cut-off.	From enrollment through study completion, assessed up to 5 years.
Positive Predictive Value of the Combined Blood-and-Urine Biomarker Score Cut-Off for Active Lupus Nephritis	Positive predictive value of the pre-specified combined blood-and-urine biomarker score cut-off for identifying active lupus nephritis. Positive predictive value will be reported as the percentage of participants with a biomarker score above the pre-specified cut-off who have active lupus nephritis.	From enrollment through study completion, assessed up to 5 years.
Negative Predictive Value of the Combined Blood-and-Urine Biomarker Score Cut-Off for Active Lupus Nephritis	Negative predictive value of the pre-specified combined blood-and-urine biomarker score cut-off for identifying active lupus nephritis. Negative predictive value will be reported as the percentage of participants with a biomarker score below the pre-specified cut-off who do not have active lupus nephritis.	From enrollment through study completion, assessed up to 5 years.
Area Under the Receiver Operating Characteristic Curve of the Combined Blood-and-Urine Biomarker Score for Incident Lupus Nephritis	AUC of the pre-specified combined blood-and-urine biomarker score for prediction of incident lupus nephritis among participants without lupus nephritis at enrollment. Incident lupus nephritis is defined as the first occurrence of lupus nephritis during follow-up according to predefined clinical criteria and kidney biopsy findings when available. The AUC will be reported as a unitless value with 95% confidence interval.	From enrollment until incident lupus nephritis, loss to follow-up, or study completion, assessed up to 5 years.
Change in Combined Blood-and-Urine Biomarker Score From Inactive Renal Disease to Active Lupus Nephritis or Renal Flare	Within-participant change in the combined blood-and-urine biomarker score between a visit classified as inactive renal disease or no renal involvement and a subsequent visit classified as active lupus nephritis or renal flare. Change will be reported in biomarker score units.	From inactive renal disease or no renal involvement visit to active lupus nephritis or renal flare visit, assessed up to 5 years.
Change in Combined Blood-and-Urine Biomarker Score From Active Lupus Nephritis or Renal Flare to Renal Response or Remission	Within-participant change in the combined blood-and-urine biomarker score between a visit classified as active lupus nephritis or renal flare and a subsequent visit classified as renal response, remission, or inactive renal disease. Change will be reported in biomarker score units.	From active lupus nephritis or renal flare visit to renal response, remission, or inactive renal disease visit, assessed up to 5 years.
Percentage of Participants With Active Lupus Nephritis Achieving Renal Response or Remission	Percentage of participants with active lupus nephritis or renal flare who achieve renal response, remission, or inactive renal disease during follow-up according to predefined protocol criteria based on proteinuria, kidney function, urinalysis, disease activity assessment, treatment status, and treating physician assessment.	From active lupus nephritis or renal flare visit through study completion, assessed up to 5 years.
Correlation Between Combined Blood-and-Urine Biomarker Score and Kidney Biopsy Activity Index	Correlation between the combined blood-and-urine biomarker score measured at the kidney biopsy or re-biopsy visit and the kidney biopsy activity index. The correlation will be reported as a correlation coefficient.	At kidney biopsy or re-biopsy visit, assessed up to 5 years.
Cumulative Incidence of Incident Lupus Nephritis	Percentage of participants without lupus nephritis at enrollment who develop incident lupus nephritis during follow-up.	Up to 5 years.

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Simin Jamaly, PhD, Oslo University Hospital

Publications and helpful links

Helpful Links

• Oslo University Hospital- clinic study

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 14, 2031
• Study Completion (Estimated): June 14, 2031

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: SLE; Systemic lupus erythematosus; Treatment response; Lupus nephritis; Kidney biopsy; Blood biomarkers; LN; Urine biomarkers; Longitudinal monitoring; Autoimmune kidney disease; Renal flare; Incident lupus nephritis; Active lupus nephritis; Renal remission; Biomarker panel
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis
• Other Study ID Numbers: 722021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be made publicly available. Access to de-identified data may be considered upon reasonable request and will be subject to ethical approvals, data protection regulations, institutional policies, and data sharing agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No