Kidney transplantation (KTX) improves mortality in patients with end stage renal disease (ESRD), but cardiovascular disease (CVD) remains the most common cause of death and kidney graft loss after KTX. Undertreated traditional CVD risk factors likely contribute to CVD progression after KTX. However, nontraditional CVD risk factors likely also contribute to CVD risk just as they do in non-transplant populations, including ESRD. Two nontraditional CVD factors, insulin resistance and inflammation, are the most likely to worsen rather than improve after KTX and often contribute to CVD in non-KTX populations. These nontraditional CVD risk factors may also be the most amenable to intervention, depending on their cause(s). Carotid intima media thickness (IMT) is commonly used as a marker of overall CVD risk and correlates with future CVD events and mortality. Carotid IMT improves in selected populations after KTX, but has never been used to evaluate CVD progression or the roles of traditional or nontraditional CVD risk factors in CVD progression in a large, unselected population of KTX recipients. This background has led us to propose the following hypothesis: """"""""Inflammation and insulin resistance are associated with CVD progression after KTX"""""""". We propose to study this hypothesis in a population of KTX recipients with the following specific aims: 1. Determine the rate and direction of CVD progression and its association with CVD events and traditional CVD risk factors;2. Correlate severity of insulin resistance with rate of CVD progression as well as with potential causes for insulin resistance;3. Correlate hsCRP as a measure of inflammation with rate of CVD progression and with potential causes of inflammation;and 4. Determine if Vitamin D and/or omega 3 fatty acid supplements improve traditional CVD risk factors, insulin resistance, inflammation, or CVD progression. This study will be the first to prospectively evaluate the impact of both traditional and nontraditional CVD risk factors on CVD progression and events over time after KTX and whether nontraditional CVD risk factors should be considered for treatment along with traditional CVD risk factors because of their contribution to CVD progression in KTX recipients. The study will also provide preliminary evidence for the efficacy of Vitamin D and omega 3 fatty acid supplementation in modifying traditional and nontraditional CVD risk factors as well as CVD progression after KTX.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK069919-04S1
Application #
7903757
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Kimmel, Paul
Project Start
2009-09-15
Project End
2011-04-30
Budget Start
2009-09-15
Budget End
2011-04-30
Support Year
4
Fiscal Year
2009
Total Cost
$99,955
Indirect Cost
Name
University of Nebraska Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Shivaswamy, Vijay; Stevens, R Brian; Zephier, Ramona et al. (2008) Dyslipidemia can be controlled in diabetic as well as nondiabetic recipients after kidney transplant. Transplantation 85:1270-6