application) Chronic renal disease is a major public health problem in the US. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality. Prevention of CVD in chronic renal disease requires early intervention, during the stage of chronic renal insufficiency (CRI). The general hypothesis for the proposed research program is that the progression of CVD and chronic renal disease share common mechanisms; and that """"""""traditional"""""""" and """"""""uremia-related"""""""" risk factors, in particular total plasma homocysteine (tHcy), lipoprotein(a) (Lp(a)) and C-reactive protein (CRP), contribute to the progression of both CVD and chronic renal disease. The Principal Investigator (PI) has designed a rigorous training program that will provide him with the necessary-skills, experience and opportunities to develop into an independent investigator in the field of cardiovascular epidemiology in chronic renal disease. He will obtain a Master's of Science in Clinical Care Research, participate in projects utilizing a broad range of study designs for clinical care research, and carry out an original research project from its inception to completion. His mentors have extensive experience in clinical investigation in nephrology, CVD epidemiology and clinical care research methodology. There are currently minimal data available on the incidence of CVD or the risk factors for CVD in CRI. The Modification of Diet in Renal Disease (MDRD) Study was the largest prospective study of patients with CRI, and is an ideal study population for the proposed research.
Specific aims are as follows: 1. Measure tHcy, Lp(a), apo(a) isoforms and CRP levels from frozen samples taken at baseline in the MDRD Study and characterize the distribution of levels and their relationship to baseline glomerular filtration rate (GFR) and other factors. 2. Determine whether baseline levels of tHcy, Lp(a), apo(a) isoforms or CRP are predictors of subsequent GFR decline. 3. Resume contact with the MDRD Study cohort, collect data on CVD and renal outcomes, and determine the relationship of traditional and uremia-related risk factors to CVD and renal outcomes. Statistical analysis reveals adequate power to evaluate each aim and a pilot study has documented the feasibility of aim 3. The PI has assembled a team of nephrologists, CVD epidemiologists, and nutrition scientists to assist him in the conduct of the project; enlisted the collaboration of the MDRD Study Data Coordinating Center, and organized internal and external advisory committees to monitor his progress. The proposed L training program and research project will prepare him for a career as an independent investigator.
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