Chronic kidney disease (CKD) has become an important public health challenge in the United States. CKD is a major risk factor for end-stage renal disease (ESRD), cardiovascular disease (CVD), and premature death. Understanding novel risk factors for the progression of CKD, CVD, and other related comorbidities may help to develop effective approaches for early intervention in order to reduce the adverse disease burden. The Chronic Renal Insufficiency Cohort (CRIC) Study is a NIDDK-sponsored multi-center prospective cohort study designed to investigate novel risk factors for the progression of CKD and development of CVD among patients with CKD. The CRIC study enrolled 3,939 patients aged 21-74 years with CKD at 7 Clinical Centers from May 2003 to March 2007, and followed-up this cohort to June 2008 during phase 1. The CRIC study extended the follow-up of study participants through April 2013 in phase 2. The CRIC Tulane Clinical Center recruited 405 study participants and achieved the highest follow-up rate among all clinical centers despite the devastation caused by hurricane Katrina in the New Orleans area. In phase 3 of the CRIC study, we propose to expand the study's scope to examine the relationship between reduced kidney function and outcomes in the elderly; to study the relationship of CKD severity and progression with a comprehensive set of outcomes beyond CVD and ESRD events; and to study the progression of kidney function decline and other clinical outcomes among patients with mild/moderate CKD. Specific aims to be addressed in phase 3 by the Tulane Clinical Center are: 1. to re-enroll a high percentage of phase 1 and 2 study participants into phase 3 of CRIC; 2. to enroll an additional 214 participants into phase 3 of CRIC; 3. to collect exposure and outcome data per the CRIC phase 3 protocol; 4. to maintain high levels of retention in the study; 5. to investigate self-reported clinical events and obtain supporting medical records and documentation; 6. to enter data and process/ship biological specimens; 7. to implement local quality assurance and quality control procedures as a means to obtain standardized, high quality measurements; 8. to monitor data collection, data entry, and follow-up rates; 9. to participate in governance and oversight of CRIC through study-wide subcommittees and activities; 10. to publish and present findings from the CRIC study; and 11. to promote and support the conduct of ancillary studies in CRIC, including collaboration with the broader nephrology research community. The proposed research has important public health and clinical implications. The study findings may reveal novel and reversible underlying etiologic factors for the progression of CKD, CVD, and other related comorbid outcomes. This information will be useful to develop further intervention studies aimed at reducing total morbidity and mortality burdens among patients with CKD.