PROJECT SUMMARY This application is submitted in response to RFA-DK-22-502, “Limited Competition: Continuation of the Chronic Renal Insufficiency Cohort (CRIC) Study (U01)” on behalf of the University of Illinois Chicago (UIC) CRIC Clinical Center. Since its inception in 2001, the CRIC Study has recruited and followed a racially and ethnically diverse cohort of 5,625 participants with reduced kidney function from 13 recruitment sites at seven Clinical Centers across the US. The original aim of CRIC was to establish a clinical research laboratory designed to (a) identify novel predictors of CKD progression, and (b) characterize the manifestations of cardiovascular disease and identify its risk factors among individuals with CKD. As the landmark prospective cohort study of CKD, the CRIC Study has accomplished extensive biological, physiological, and social phenotyping, longitudinal follow- up, and ascertainment of 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. During the most recent funding cycle (Phase 4: 2018-2023), three innovative sub-protocol 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 focus will be to (1) ascertain the clinical outcomes for all participants including those enrolled in the Phase 4 sub-protocols, (2) perform analyses linking the sub-protocol measurements to clinical outcomes, (3) integrate data from multiple domains to identify sub-phenotypes 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, (6) generate tools and resources to facilitate ongoing use of CRIC data and biospecimens by a broad group of investigators, and (7) support UIC CRIC participant enrollment into the recently funded UIC Kidney Precision Medicine Project (KPMP) CKD Recruitment Site. During the first four phases of the CRIC Study, the UIC research team enrolled nearly 1,200 participants and has been successful in retention, protocol implementation, data quality, and scientific productivity. Additional noteworthy achievements include a strong focus on heath disparities in CKD, a significant number of UIC investigator-led publications, leadership on funded ancillary studies, and the promotion of new physician-scientists. Consequently, the UIC team is well positioned to make a substantive contribution to the consortium by generating new scientific output and successfully transitioning the CRIC Study from its active prospective cohort phase to a long-lasting resource for supporting ongoing and future mechanistic, epidemiologic, and translational investigations.

PROJECT NARRATIVE The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled more than 5500 adults with chronic kidney disease (CKD) to address overarching goals of identifying predictors of rapid progression of kidney disease and clarifying the relationship between kidney disease and the risks of cardiovascular events and death. During the earlier phases of CRIC, the UIC Clinical Center research team has been successful in terms of recruitment, retention, data quality, a strong focus on heath disparities in CKD, and scientific productivity. This proposal for the next phase will extend follow-up for another three years during which we will conduct data analyses with integration of findings from home testing done during the prior phase, and final study visits.