The National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) established the Chronic Renal Insufficiency Cohort Study in 2001. The principal goals of the CRIC Study are to examine risk factors for chronic kidney disease (CKD) progression (i.e. further loss of kidney function) and cardiovascular events among patients with varying severity of CKD, and develop predictive models that will identify high-risk subgroups with CKD. The latter results will target enrollment of high-risk subjects into future treatment trials and increase application of available preventive therapies. Hypertension treatment has been an effective intervention altering the course of renal function loss in CKD. However, the recent findings of the African American Study of Kidney disease suggest that kidney function loss and cardiovascular events occur despite excellent blood pressure control on regimens that block the renin- angiotensin system. This raises the possibility that interventions that go beyond blood pressure reduction are necessary to halt the progression of CKD and prevent incident cardiovascular disease (CVD). Available data suggest that large artery stiffness plays a role in both kidney dysfunction and CVD. Determination of aortic pulse wave velocity (PWV;the gold standard measure of large artery stiffness) and central pulse pressure are novel methodologies that have provided useful information in cardiovascular disease epidemiology. We propose to use these methods to study both CVD as well as progressive kidney function loss in the already recruited CRIC population anticipating that this will contribute to narrowing the knowledge gap between vascular function and kidney/cardiovascular outcomes. We hypothesize that aortic pulse wave velocity predicts kidney and CVD outcomes in subjects with CKD. We propose to test this hypothesis with three specific aims:
Specific Aim 1 : To determine pulse wave velocity in a heterogeneous cohort of subjects with chronic kidney disease.
Specific Aim 2 : To determine the utility of pulse wave velocity to predict of renal failure progression in a CKD cohort.
Specific Aim 3 : To determine the utility of pulse wave velocity to predict cardiovascular outcomes in a CKD cohort.
These aims will be carried out in a population of 3000 individuals, 50% with diabetes, recruited at clinical centers in the USA beginning in 2003. All data derived from this study are managed at the University of Pennsylvania by the Science Data Coordinating Center (SDCC). The techniques employed involve minimal risk to subjects and a modest burden of time to perform. Kidney function and CVD are carefully measured pre-specified endpoints in CRIC. Improved recognition of etiological factors in CKD progression and cardiovascular endpoint occurrence will inform the development and testing of interventions to reduce the burden of advanced kidney failure and cardiovascular morbidity and mortality.

Public Health Relevance

Chronic kidney disease progresses in many people making dialysis necessary. Many of these patients also have heart disease. Treating blood pressure mitigates some but not all of these effects, despite good blood pressure control. Since the target organs of hypertension (kidney,heart,brain) are linked by the circulation this project evaluates specific aspects of the circulation which may be important in disease progression.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-S (O2))
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Kusek, John W
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Chirinos, Julio A; Khan, Abigail; Bansal, Nisha et al. (2014) Arterial stiffness, central pressures, and incident hospitalized heart failure in the chronic renal insufficiency cohort study. Circ Heart Fail 7:709-16
DeLoach, Stephanie S; Meyers, Kevin E C; Townsend, Raymond R (2012) Living donor kidney donation: another form of white coat effect. Am J Nephrol 35:75-9
Budoff, Matthew J; Rader, Daniel J; Reilly, Muredach P et al. (2011) Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis 58:519-26
Scialla, Julia J; Leonard, Mary B; Townsend, Raymond R et al. (2011) Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease. Clin J Am Soc Nephrol 6:2612-9
Townsend, Raymond R; Sica, Domenic A (2011) Beyond conventional considerations: newer devices used in blood pressure measurement and management. Adv Chronic Kidney Dis 18:48-54
Rubin, Mario F; Rosas, Sylvia E; Chirinos, Julio A et al. (2011) Surrogate markers of cardiovascular disease in CKD: what's under the hood? Am J Kidney Dis 57:488-97
Townsend, Raymond R; Chirinos, Julio A; Parsa, Afshin et al. (2010) Central pulse pressure in chronic kidney disease: a chronic renal insufficiency cohort ancillary study. Hypertension 56:518-24
Townsend, Raymond R; Wimmer, Neil J; Chirinos, Julio A et al. (2010) Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens 23:282-9
DeLoach, Stephanie S; Joffe, Marshall M; Mai, Xingchen et al. (2009) Aortic calcification predicts cardiovascular events and all-cause mortality in renal transplantation. Nephrol Dial Transplant 24:1314-9
DeLoach, Stephanie S; Appel, Lawrence J; Chen, Jing et al. (2009) Aortic pulse pressure is associated with carotid IMT in chronic kidney disease: report from Chronic Renal Insufficiency Cohort. Am J Hypertens 22:1235-41

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