Non-traditional Factors and Cardiovascular Disease on Patients with Chronic Kidney Disease
Dates: 1/1/14 – 5/31/17
Co-Investigators: Houry Puzanian, Lauretta Quinn, James Lash, Raymond Townsend
Abstract: More than twenty million people in the United States have chronic kidney disease (Coresh et al., 2007). Cardiovascular disease (CVD) is the leading cause of mortality, across the spectrum of kidney disease stages (United States Renal Data System, (USRDS), 2009). Most CKD patients experience cardiovascular events and death prior to advancing into kidney failure requiring dialysis or transplantation. Furthermore, younger patients with CKD have a cardiovascular event risk that approximates that in the older general population, and a higher relative risk than older CKD patients. This suggests a CKD-related accelerated vascular aging or cardiovascular risk profile in younger patients. These facts highlight the importance of addressing CVD in patients with CKD early on, in mild to moderate kidney disease.
Pulse wave velocity (PWV) is a widely used marker of arterial stiffness, and an independent predictor of cardiovascular events. Additionally, albuminuria indicates increased likelihood of CKD progression and cardiovascular event risk. Identifying pathophysiologic mechanisms that correlate with CVD measures (i.e., PWV and albuminuria) may provide opportunities for primary prevention of CVD in CKD patients. Increased serum levels of asymmetric dimethylarginine (ADMA) and matrix metalloproteinase-2 (MMP2) contribute to the development of vascular dysfunction albeit by different mechanisms of endothelial dysfunction and interference with connective tissue turnover. Therefore, the main purpose of this study is to determine if baseline serum levels of ADMA and MMP2 are associated with longitudinal changes in carotid-femoral PWV(cfPWV) and albuminuria in CKD, prior to dialysis or transplantation. This investigation may elucidate novel targets for prevention of cardiovascular outcomes in the CKD population.
We will take advantage of the Chronic Renal Insufficiency Cohort (CRIC) established in 2011 by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to improve the understanding of CKD and related CV illness. Funds from UIC-CRB will be used to measure ADMA and MMP2 in previously collected CRIC blood samples, in a patient subgroup with PWV and albuminuria measures already available in the CRIC database.