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.
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
500
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.
Oslo universitetssykehus HF, Rikshospitalet, Clinic for Surgery and Specialized Medicine, Department of Rheumatology, Skin and Infectious Diseases
Oslo, Oslo, Norway
RECRUITINGArea 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.
Time frame: From enrollment through study completion, assessed up to 5 years.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 5 years.
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