Pulse wave velocity in chronic kidney disease

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DESCRIPTION (provided by applicant): 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 the most effective intervention altering the course of renal function loss in CKD. However, the drugs used in the treatment of hypertension differ in their benefits on renal function. This raises the possibility that blood pressure reduction by itself only partly explains their beneficial effect and beckons a broader understanding of vascular adaptation to diseases such as CKD. Determination of the pulse wave velocity (PWV) a reflection of large vessel stiffness has provided useful information in cardiovascular disease epidemiology. We hypothesize that pulse wave velocity predicts progression in subjects with chronic kidney disease, which we propose to test 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 7 clinical centers in the USA recruited over 30 months beginning in 2003. All data derived from this study will be managed here at Penn in cooperation with the Center for Biostatistics and Epidemiology. The techniques employed involve no risk to subjects and a minimal burden of time to perform. This revised application presents data on technique reproducibility, expanded preliminary data, tile incorporation of central augmentation index measures, and revised analysis & power sections that address tile many important issues raised by the critiques from tile first review. Improved recognition of etiological factors in CKD progression and cardiovascular endpoint occurrence will permit development and testing of interventions to reduce the burden of advanced renal failure and cardiovascular morbidity and mortality.