Racial and Cardiovascular Risk Factor Anomalies in CKD

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DESCRIPTION (provided by applicant): Among individuals with chronic kidney disease (CKD) receiving maintenance dialysis therapy the proportion of African American patients is significantly higher compared to their non-Hispanic white counterparts, and traditional risk factors of cardiovascular disease such as hypercholesterolemia, hypertension and obesity show seemingly anomalous, inverse associations with adverse outcomes. The exceptionally high prevalence of end- stage renal disease (ESRD) among African Americans is likely a result of the complex interaction of their higher rates of CKD incidence and/or faster CKD progression, lower mortality, and lower likelihood of kidney transplantation. The anomalous cardiovascular risk factor profile in ESRD could be the result of short-term competing risks related to malnutrition and inflammation, with the seemingly unfavorable traditional cardiovascular risk factors associating with a better nutritional state, which could differentially affect African Americans an hence provide one explanation for their better survival in ESRD. Whether similar paradoxical differences in mortality rates in non-dialysis dependent CKD stages exist is not clear; their presence, extent, the CKD stage of its occurrence and their mechanisms of action all need to be clarified in sufficient detail to allow for the design of proper diagnostic and interventional strategies towards cardiovascular risk reduction and towards alleviating racial disparities in outcomes. In the spirit of PA-09-196 we will utilize data obtained from the national VA research database which is the only large administrative database with detailed socio-demographic and clinical information on very large numbers of individuals (over 4 million individuals including ove 0.5 million with CKD) across all parts of the US. We will examine the population-wide dynamic effects of incident CKD and mortality on racial composition and on changes in cardiovascular risk factor profiles by examining longitudinally a cohort of patients with normal estimated glomerular filtration rate. We will explore the effects of various socio-demographic characteristics, co-morbidities, biochemical measurements and medication use on mortality and progressive CKD using complex epidemiologic methods including joint modeling to assess the effect of longitudinal changes in risk factor parameters on mortality and marginal structural models in order to adjust for both baseline and time-dependent confounders. This three-year project will generate a wealth of information to more reliably examine the above hypotheses related to racial and cardiovascular discrepancies in the outcomes of patients with all levels of kidney function that could have significant public health implications.