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Lupus nephritis is a serious complication of systemic lupus erythematosus and a major driver of morbidity and mortality. Current clinical monitoring relies heavily on proteinuria and kidney biopsies—tools that are limited in their ability to detect active intrarenal inflammation. This presentation will highlight emerging data supporting urine proteomics as a non-invasive approach for diagnosing, monitoring, and prognosticating lupus nephritis.Urine proteomic signatures can distinguish proliferative from membranous lupus nephritis and correlate closely with histologic activity.1 Several key biomarkers reflecting intrarenal immune activation have diagnostic utility and can predict treatment response as early as 3 months into therapy—outperforming proteinuria in forecasting 1-year response.2 A validated multi-protein panel can reliably identify histologically active lupus nephritis and holds promise as a surrogate endpoint in clinical trials. Most importantly, urine proteomics offers a novel response biomarker: the decline of inflammatory markers not only aligns with biological plausibility, reflecting resolution of renal inflammation, but also predicts long-term kidney survival—the true goal of lupus nephritis treatment.3. This approach could transform lupus nephritis management by enabling precision medicine through real-time, non-invasive assessment of kidney inflammation, reducing reliance on invasive biopsy, and improving therapeutic guidance.References Fava A, Buyon J, Magder L, et al. Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis. JCI Insight. 2024;9(2) doi: 10.1172/jci.insight.172569Fava A, Buyon J, Magder L, et al. Op0211 change in urinary biomarkers at three months predicts 1-year treatment response of lupus nephritis better than proteinuria. Ann Rheum Dis. 2023;82(Suppl 1):138. doi: 10.1136/annrheumdis-2023-eular.2034Fava A, Atta M, Monroy-Trujillo J, et al. Op0228 persistence of urinary biomarkers of intrarenal inflammation precedes loss of kidney function in lupus nephritis. Ann Rheum Dis. 2024;83:18. doi: https://doi.org/10.1136/annrheumdis-2024-eular.3068Learning Objectives At the end of this presentation participants will be able to:Describe the limitations of current clinical monitoring tools for lupus nephritis and explain how urine proteomics offers a non-invasive approach to assess intrarenal inflammationIdentify key applications of urine proteomic signatures, including their ability to distinguish lupus nephritis subtypes, correlate with histologic activity, and predict treatment responseDiscuss the potential impact of urine proteomics on lupus nephritis management, specifically its role in enabling precision medicine, reducing reliance on kidney biopsies, and improving long-term therapeutic guidance