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.

• Area Under the Receiver Operating Characteristic Curve of the Urinary Biomarker Score for Active Lupus Nephritis [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: At kidney biopsy or re-biopsy visit, assessed up to 5 years.]
• Cumulative Incidence of Incident Lupus Nephritis [Срок оценки: Up to 5 years.]