There is a substantially higher incidence of cardiovascular events and cardiovascular deaths in the chronic kidney disease (CKD) population compared to the general population. However, there are several unresolved questions regarding the mechanisms that lead to increased cardiovascular events in the CKD population. It remains unclear 1. whether CKD by itself leads to accelerated atherosclerosis and 2. What the relative contribution of traditional and non-traditional risk factors to progression of atherosclerosis in CKD are. As the Systolic Pressure Intervention Trial (SPRINT) has a unique design of enrolling a large number of CKD and non-CKD participants at high risk for atherosclerotic events, this trial provides a great opportunity to examine whether atherosclerosis progression is accelerated in CKD compared to non-CKD and the factors that contribute to the greater prevalence of atherosclerosis in CKD. Therefore, in this ancillary study to SPRINT, we propose to examine (1) Whether there is a faster rate of progression of atherosclerosis in CKD compared to the non-CKD population and (2) Whether abdominal obesity and factors reflective of abnormal bone and mineral metabolism (plasma calcium, phosphorus, alkaline phosphatase, 25 and 1,25 vitamin D and fibroblast growth factor 23 levels) play a significant role in progression of atherosclerosis or calcification of atheromatous plaques in the CKD population. SPRINT, a large scale randomized trial of ~ 9250 adults aged 55 years or older with high cardiovascular risk will test the effects of low SBP goal of <120 mm Hg vs. the standard goal of <140 mm Hg on the primary composite of cardiovascular events and death. SPRINT is expected to start enrolling patients in Oct, 2010. SPRINT will recruit 45% of the study population with CKD. For this ancillary study, 480 SPRINT participants (240 with CKD and 240 without) will be recruited in 6 SPRINT sites. These sites include the University of Utah, Stanford University, University of Colorado at Denver, Case Western Reserve University, Cleveland Clinic and the University of Pittsburgh. Following standardized protocols, participants will undergo carotid MRI to measure atherosclerosis at baseline and 30 months. These images will be read by the Carotid MRI Reading Center at the University of Washington. Blood and urine samples will be carefully collected, processed and stored at baseline, 12 and 30 months. Assays will be performed at University of Minnesota and the University of Utah. Statistical analyses will be conducted at the SPRINT Coordinating Center at the Wake Forest University. We believe the strengths (the unique opportunity to examine a large number of CKD and non-CKD participants, the importance of the questions to be examined, the strength of the investigative team and the availability of resources) of this proposal will lead to successful conclusion of the ancillary study and the results will guide designing future RCTs targeting atherosclerosis in CKD.

Public Health Relevance

People with chronic kidney disease have a higher risk of cardiovascular events, but the mechanisms are not well understood. The proposed project will address this important issue and provide insights into designing interventional studies to improve the outcomes of chronic kidney disease patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK091437-02
Application #
8313947
Study Section
Special Emphasis Panel (ZDK1-GRB-C (J1))
Program Officer
Kimmel, Paul
Project Start
2011-08-05
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$598,650
Indirect Cost
$86,868
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Kaskel, Frederick; Batlle, Daniel; Beddhu, Srinivasan et al. (2014) Improving CKD therapies and care: a National Dialogue. Clin J Am Soc Nephrol 9:815-7