CHRONIC KIDNEY DISEASE AND CARDIOVASCULAR RISK IN BLACK AND WHITE YOUNG ADULTS (Cystatin C -CC 08-09)

Blacks are disproportionately affected by chronic kidney disease (CKD). Although rates of prevalent CKD are similar between Blacks and Whites, Blacks have higher rates of age-adjusted incident CKD and experience more rapid progression to end stage renal disease. Blacks also have high rates of cardiovascular disease, particularly heart failure, a known complication of CKD. Identifying the antecedents to CKD and the factors leading to rapid progression of CKD and its cardiovascular complications is important for guiding preventive efforts and decreasing health disparities in this high-risk population. Prior studies in this area have been limited by the use of creatinine-based measures of function that may be poorly reflective of modest decrements in function and thus mask early kidney disease, and by the lack of longitudinal data on cohorts with an adequate number of young to middle-aged Black participants without prevalent disease. Cystatin C is a cysteine proteinase inhibitor whose plasma levels are strongly correlated with glomerular filtration rate (GFR) over a wide range of kidney function. Cystatin C levels may be more sensitive than creatinine-based measures for detecting early declines in kidney function and for predicting cardiovascular events, particularly among individuals without CKD (GFR 60 ml/min/1.73m2). We propose to measure cystatin C at multiple time-points in Coronary Artery Risk Development in Young Adults (CARDIA), an NI-ILBI funded cohort of young adults with similar numbers of Black and White individuals with 20 years of follow-up. As a cohort without prevalent disease at baseline, CARDIA offers the unique opportunity to investigate CKD onset, progression, and cardiovascular complications. Black CARDIA participants have developed higher rates than Whites of kidney dysfunction (4-fold higher for Blacks), heart failure (10- fold higher), and hypertension (2- fold higher), making this cohort ideal for exploring those factors that place Black individuals at particular risk for CKD, cardiovascular disease, and associated risk factors. This proposal will use the longitudinal design of CARDIA to address the following specific aims: Aim 1: To evaluate declines in kidney function - as measured by cystatin C - in a balanced cohort of Black and White young men and women. - Hypothesis 1.A: Blacks will experience a greater decline in kidney function than Whites. - Hypothesis 1.B: The greater decline in kidney function in Blacks will be mediated by elevated systolic blood pressure and socioeconomic factors. - Hypothesis 1.C: The greater decline in kidney function in Blacks will be mediated by systemic inflammation. - Hypothesis 1.D: Cystatin C concentrations will be superior to creatinine-based estimates of GFR for predicting subsequent development of CKD (GFR <60 ml/min/1.73m2). Aim 2: To determine the association between kidney function assessed by cystatin C concentration and subsequent sub-clinical cardiovascular disease. - Hypothesis 2.A: Cystatin C concentration will be associated with subsequent measures of sub-clinical cardiovascular disease. - Hypothesis 2.B: Cystatin C concentration will be more strongly associated with carotid intima media thickness in Blacks than in Whites, whereas cystatin C concentration will be more strongly associated with coronary artery calcium in Whites than in Blacks. - Hypothesis 2.C: Cystatin C concentration will be a better predictor of subsequent sub-clinical cardiovascular disease than creatinine-based measures or microalbuminuria. Aim 3: To determine the association between kidney function as assessed by cystatin C concentration and incidence of clinical cardiovascular disease. - Hypothesis 3.A: Increasing cystatin C concentration will be associated with greater risk, for subsequent cardiovascular disease events. - Hypothesis 3.B: Cystatin C concentration will be a better predictor of subsequent clinical cardiovascular disease than creatinine-based measures or microalbuminuria.

PI: Dale Williams, PhD