Hypertension (HTN) and chronic kidney disease (CKD) are two highly prevalent and strong risk factors for cardiovascular disease (CVD) that are linked via common risk factors and pathophysiology. Specifically, arteriosclerosis of the preglomerular arterioles leads to relative renal ischemia and subsequent activation of the rennin-angiotensin system ultimately leading to increases in blood pressure. In this proposal, we hypothesize that local (i.e. renal artery) subclinical atherosclerosis is significantly and independently associated with kidney function, blood pressure, hypertension and incident CVD events. Using the Aortic Calcium subsample of 1970 subjects from the Multi-Ethnic Study of Atherosclerosis (MESA), the specific aims for this study are to determine if: 1) Renal artery calcium (RAC) is associated with kidney function, as measured by a) glomerular filtration rate, b) cystatin-C and 3) urine albumin;2) Both baseline and prospective changes in RAC are significantly associated with changes in kidney function and incident CKD over approximately 3 years of follow-up;3) RAC is associated with four blood pressure (BP) measures: a) systolic BP, 2) diastolic BP 3) pulse pressure and 4) mean arterial pressure, as well as the diagnosis of hypertension;4) RAC is significantly associated with both incident hypertension and cardiovascular disease events. If so, we will determine if this association is mediated by differences in kidney function. We will explore these aims by interrogating images from computed tomography (CT) scans of the abdomen. The abdominal CT images will be scored for RAC, kidney volume and kidney density at the MESA CT reading center at UCLA. Blood samples will be assayed for cystatin-C, renin and aldosterone. The cystatin-C results will be used as a measure of kidney function and compared with existing data on serum creatinine and urine albumin. Renin and aldosterone will be used to determine if the presence of RAC is associated with differences in the rennin-angiotensin-aldosterone system. Approximately 700 of the subjects will have had follow-up scans completed by July 2007 allowing for testing of hypotheses involving prospective changes in RAC and kidney function. Finally, the overrepresentation of ethnic minority groups in MESA will allow for testing of interactions with ethnicity. We are unaware of any other population-based study adequate to study the stated aims.
Hypertension and chronic kidney disease are two very prevalent diseases that are also strong risk factors for cardiovascular disease (CVD). In this study of nearly 2,000 individuals from 4 major ethnic groups, we propose to determine if early disease of the arteries leading to the kidneys is associated with decreases in kidney function and the development of hypertension. The results of this study may have implications for the prevention of high blood pressure and kidney disease.
