ABSTRACT Lupus remains a leading cause of death in young women, with racial/ethnic minority patients having worse long-term outcomes, including progression to end stage renal disease and overall mortality, and poorer intermediate outcomes of disease activity and damage accrual. Further, manifestations of lupus affect physical function, fatigue, pain, and other patient-reported outcomes, potentially leading to challenges with maintaining everyday activities and function, which are linked to better quality of life, productivity, and survival. Finally, a major challenge in SLE management is delayed identification of early kidney disease, which ultimately leads to a greater burden on both patients and the health system. In response to the CDC NOFO RFA-DP-22-002, Component A, “Epidemiology of Lupus: Longitudinal Studies in Population-Based Cohorts,” this proposal leverages our well-established, longitudinal, ethnically/racially and socioeconomically diverse, and phenotypically well-characterized cohort of patients with lupus. This proposal’s overarching goals include clarifying the long-term natural history of SLE by evaluating disease severity, morbidity, and multi-morbidity; assessing disparities in illness experience associated with race/ethnicity, age, and socioeconomic status; collecting novel biospecimens to potentially differentiate roots of pain/fatigue syndromes; and evaluating a novel strategy to identify early kidney disease in high-risk patients. The NYU Lupus Cohort is a “living” biorepository with >900 patients enrolled, three-quarters followed at least twice annually, with diverse backgrounds (50% minority race; 30% Hispanic) and socioeconomic status (31% public hospital patients) who provide samples over time. Data include demographics, established classification criteria over time, medications, routine metabolic and hematologic parameters, laboratory-based urine analysis, autoantibody profiles, disease activity fluctuations and organ damage accrual using validated instruments, patient-reported outcomes, and measures for socioeconomic status and position, and material, behavioral, psychosocial, health system, and health outcomes. We propose to extend our longitudinal Cohort with linkage to electronic health records and state-wide, all-payer claims data for comorbidity data, new cytokine profiles and transcriptomic modules, and implementating a novel strategy to identify early kidney disease. Our multidisciplinary team will address three Specific Aims: 1) Quantify multimorbidity and major healthcare use in patients with lupus to improve understanding of lupus and non-lupus comorbidities, including disparities by sociodemographic factors; 2) Measure the burden of lupus on quality of life, with analyses to assess disparities by sociodemographic factors, behavioral and psychosocial factors, and genetic information; and 3) Develop and evaluate innovative, technology-driven home-based proteinuria testing for patients at elevated risk of neph...