PROJECT SUMMARY This application is submitted by the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania to serve as the Scientific and Data Coordinating Center (SDCC) for Phase 5 of the Chronic Renal Insufficiency Cohort (CRIC) Study. Since its inception in 2001, the CRIC Study has enrolled and followed a racially and ethnically diverse cohort of 5,625 individuals with reduced kidney function at 7 Clinical Centers across the United States. As the landmark prospective evaluation of CKD, the CRIC Study has performed extensive and deep biological, physiological, and social phenotyping, and ascertained longitudinal clinical and patient-centered outcomes across multiple domains. Findings from the CRIC Study have defined trajectories of CKD progression, catalogued development and evolution of comorbidities in CKD, and identified a diverse array of factors and pathways that explain the progression and complications of CKD in adults. Through its highly productive Ancillary Studies and Opportunity Pool Programs, both the scientific scope of the CRIC Study and the community of kidney disease researchers have been markedly expanded. During the most recent funding cycle (Phase 4: 2018-2023), three innovative subprotocol studies were implemented to enrich CRIC data with highly granular home-based assessments of kidney function and cardiovascular measures. During the fifth and final phase of the CRIC Study, the major goals will be to (1) ascertain the clinical outcomes for all participants including those enrolled in the Phase 4 subprotocols, (2) perform analyses linking the subprotocol measurements to clinical outcomes, (3) integrate data from multiple domains to identify subphenotypes underlying the heterogeneity in CKD progression outcomes, (4) conduct final study visits for the full CRIC cohort eligible for Phase 5, (5) create mechanisms for future data collection via linkages with external sources of health data, and (6) generate tools and resources to facilitate ongoing use of CRIC data and biospecimens by a broad group of investigators after the CRIC Study has formally ended. An important product of the Phase 5 analytical activities will be a data-driven holistic CKD framework that will depict the complex interplay of contributors to CKD progression and cardiovascular complications, inform patient care, and guide the design of future clinical trials. The SDCC, led by a highly experienced team of investigators from the University of Pennsylvania, Tulane University, and Northwestern University, will provide scientific and operational leadership to ensure that the CRIC Study Group achieves these goals. The proposed activities, coordinated between the Clinical Centers and the SDCC, will generate new scientific output and successfully transition the CRIC Study from its active, prospective cohort phase to a long-lasting resource for supporting ongoing and future mechanistic, epidemiologic, and translational investigations.