ABSTRACT Between 2001-2018, the NIDDK sponsored Phases I, II and III of the Chronic Renal Insufficiency Cohort (CRIC) Study in which approximately 3,939 multiethnic, adult participants were enrolled from seven clinical centers and their satellites, along with 1560 patients who were older with milder chronic kidney disease (CKD). An additional 326 participants of Hispanic ethnicity with chronic kidney disease (CKD) were recruited from one clinical center The cumulative total of 5,499 study participants has been followed for 2-14 years during which we aimed to: (1) examine the risk factors for CKD progression and cardiovascular disease (CVD); (2) study the relationship between CKD and outcomes in the elderly; (3) evaluate the CKD and CVD outcomes in participants with CKD stage 2 and 3 A (mild/moderate CKD); (4) develop predictive models to identify high risk subgroups; and (5) identify biomarkers which predict disease progression and complications. The goals of the current proposal are to: (1) continue the follow-up of the originally recruited CRIC cohort; (2) study the relationship between sub clinical acute declines in kidney function and CKD outcomes; (3) Conduct a comprehensive assessment of the morbidity experienced by participants with CKD including CVD clinical outcomes by the use of remote data capture. In CRIC 2018-2023, the Michigan CRIC Clinical Center will undertake the following specific aims: 1. To re-enroll a high percentage of existing participants into CRIC 2018 and obtain clinical center-based assessments (questionnaires, physical measurements, biological specimens) in study participants. 2. To maintain high levels of participant retention during CRIC 2018. 3. To identify novel cardiovascular phenotypes using remotely collected cardiovascular function and determine their relationship to clinical outcomes. 4. To examine sub-clinical acute declines in kidney function using remotely collected kidneys function outside of the clinical center and determine their relationship to clinical outcomes. 5. To investigate self-reported cardiovascular and renal events and obtain supporting medical records and documentation. 6. To implement effective local quality assurance and quality control procedures to ensure standardized high-quality measurements. 7. To participate in governance and oversight of CRIC through study-wide subcommittees and activities 8. To publish and present findings from the CRIC Study, including integrative and other high-impact manuscripts, as chairs and members of CRIC writing groups. 9. To conduct approved CRIC ancillary studies at the Michigan Clinical Center. 10. To facilitate state-of-the-art methods in biostatistics and bioinformatics to analyze complex, longitudinal datasets incorporating a multitude of exposure and outcome variables to produce integrated papers. 11. To engage investigators at the University of Michigan Health Systems, to assist in the local analysis of CRIC data, to develop and conduct ancillary studies, and to participate in parent study activities. 12. To engage investigators in the broader scientific community to analyze data locally, to develop and conduct ancillary studies, and to participate in the parent study. It is estimated that 485 of the Michigan CRIC Phase III participants will be eligible to participate in CRIC 2018- 2023 of which 65 participants will be from the Hospitals of the Wayne State University School of Medicine. In addition, we will continue to execute a prospective assessment of morbidity and causes of hospitalization and resource utilization in all the participants. Our Clinical Center will cooperate with other CRIC study awardees and the NIDDK in the implementation of study protocols and procedures to accomplish the specific aims outlined above.

NARRATIVE This project will study nearly 3500 patients to better understand the factors and pathways leading to end stage kidney failure, cardiovascular disease and premature death in individuals with diminished kidney function. Understanding the mechanism of progression of chronic kidney disease and its relationship to cardiovascular disease will advance the Objective 4-1 of Health People 2010 to improve the renal health of Americans.