Biomarker Development for Autoimmune Disorders Involving the Kidneys

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.

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