This is an application from the Center for Clinical Epidemiology and Biostatistics at the University of Pennsyl- vania to serve as the Scientific and Data Coordinating Center (SDCC) for the continuation of the Chronic Renal Insufficiency Cohort (CRIC) Study. Chronic renal insufficiency affects over 20 million Americans with particular burden among older adults. The morbidity associated with chronic kidney disease (CKD) derives from frequent progression to end-stage renal disease (ESRD), a disproportionate risk of cardiovascular events, and other morbidities associated with disability and high costs of care. Since its inception in 2001, the CRIC Study has recruited and followed a racially and ethnically diverse cohort of over 5,000 participants with reduced kidney function from 13 clinical recruitment sites 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. The CRIC Study has examined a broad set of etiological factors (clinical, behav- ioral, and biomarker-associated) potentially responsible for both progressive CKD and morbidities in the setting of CKD, especially those operating early in the course of CKD when progression may be forestalled. Charac- terizing relationships between these risk factors and outcomes will permit identification of high-risk subgroups with CKD, guiding enrollment into preventive treatment trials and application of preventive therapies. Over time, the scientific focus and the CRIC investigator network have broadened extensively through a highly suc- cessful ancillary studies program that has included 90 projects, mostly federally funded. To date, the CRIC Study's investigative activities have resulted in over 150 published scientific papers with many additional man- uscripts in development addressing clinical outcomes in the setting of CKD. To maximize the opportunities inherent in this unique scientific resource, the CRIC Study will, in its next phase, pursue a multifaceted strategy involving: (a) continued follow-up of the cohort and investigation of a broad ar- ray of factors associated with the progression and consequences of CKD utilizing state-of-the-art methods in biostatistics and bioinformatics; (b) the use of novel remote data collection techniques to identify trajectories of kidney function and cardiovascular risk sub-phenotypes; (c) regular data sharing with CRIC Clinical Centers to facilitate new collaborative partnerships, promote innovative scientific inquiry, and support professional devel- opment of CKD researchers; (d) facilitating disseminated analysis of CRIC data by frequent and comprehen- sive updates to the NIDDK Data Repository, supplementation of the Repository's user support activities, and robust outreach to the broader research community; (e) coordination of the goals and activities of the CRIC Study with the Kidney Precision Medicine Project and other NIH-sponsored projects; and (f) the establishment and administration of an Opportunity Pool of funds for investigators external to the CRIC study.

Project Narrative The CRIC Study is a national multi-center evaluation of the factors associated with disease progression and morbidity within a diverse population of Americans with varied forms of chronic kidney disease (CKD), a condition that affects approximately 15% of the US population. In its next phase, the CRIC Study will continue its examination of the effect of a broad range of risk factors (from molecular biomarkers of disease pathways to clinical, demographic, and behavioral characteristics) on the progression of CKD and other health consequences, and will, in addition, develop and carry out novel approaches to deep phenotyping in CKD made possible by the use of cutting-edge remote data capture technologies, focusing on (a) home measurement of serum creatinine and urine protein to examine trajectories of kidney function, and (b) ambulatory measurement of physical activity and cardiovascular (CV) parameters to identify sub-phenotypes of CV risk. The CRIC Study will also maintain and expand its role as a resource to the broader research community by (a) continuing its support of ancillary studies, (b) providing datasets to be used for disseminated analyses at the CRIC Clinical Centers and in the research community at large, (c) establishing and administering an Opportunity Pool of funds to be competitively awarded to outside investigators for the purpose of performing CKD research, and (d) carrying out integrative analyses designed to generate insights into the causes, course, and consequences of CKD that will form the basis for subsequent clinical trials and interventions.