Gender Disparities and Vascular Function in Chronic Kidney Disease Outcomes

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DESCRIPTION (provided by applicant): The candidate for this Mentored Patient-Oriented Research Career Development Award (K23) is Ana C. Ricardo, MD, MPH, a nephrologist at the University of Illinois at Chicago (UIC). Dr. Ricardo's short-term goals are to gain experience and develop skills by conducting research focused on gender disparities in chronic kidney disease (CKD), and the contribution of gender differences in endothelial function to these disparities. Her long-term career goals are to become an independent investigator conducting research focused on reducing health inequalities in CKD through lifestyle interventions. To achieve her goals, Dr. Ricardo has assembled a comprehensive career development plan that consists of mentored research and didactic coursework at the UIC School of Public Health. Dr. Ricardo's strong team of mentors and collaborators includes world-class experts with longstanding NIH funding and extensive mentorship experience. Her primary mentor, James P. Lash, MD, is an expert in the epidemiology of CKD in minority populations; Martha L. Daviglus, MD, PhD, her co-mentor, has expertise in the epidemiology of cardiovascular disease. The proposal also includes a multidisciplinary team of collaborators with expertise in the areas of women's health, longitudinal data analyses, and the influence of exercise on vascular function. Dr. Ricardo's successful development into an independent physician-scientist will be facilitated by the extensive facilities and resources available at UIC which include the Clinical and Translational Science Award, the Center for Research on Women and Gender, and the School of Public Health. Dr. Ricardo's research will advance her skills in both primary data collection and longitudinal data analyses. The proposal leverages the infrastructure of the NIH- funded Chronic Renal Insufficiency Cohort (CRIC) Study, a large and diverse observational study of adults with CKD. Evidence suggests that there are significant gender-related disparities in CKD. Whereas data from the United States Renal Data System indicate that men have 1.5 times greater incidence of end-stage renal disease, a higher prevalence of CKD in women was seen in the National Health and Nutrition Examination Survey. Several studies suggest that men have more rapid CKD progression, but this has not been a consistent finding. Furthermore, previous studies were not designed to address this question and included few racial/ethnic minorities. In the general population, there is evidence that differential rates of cardiovascular outcomes in women and men may be related to gender differences in endothelial function, which have been in part attributed to the protective effect of estrogen in women. Moreover, limited data suggest that endothelial dysfunction may be a predictor of CKD progression. However, the contribution of endothelial function to gender disparities in CKD progression is not known. This is an area of significance because studies of non-CKD populations suggest that endothelial function may be improved with pharmacologic therapy (e.g., ACE- inhibitors) or lifestyle interventions (e.g., exercise). The specific aims for the proposed project are to 1) Examine gender disparities in kidney and cardiovascular outcomes in the CRIC Study; 2) Examine gender differences in endothelial function and the role of endothelial function as a predictor of CKD progression in 150 University of Illinois CRIC Study participants; and 3) Evaluate the feasibility of a 12-week pilot resistance exercise training intervention and its effect on endothelial function and cardiovascular risk factors in men and women with CKD. This Career Development Award will provide the foundation for Dr. Ricardo to pursue an independent research career dedicated to reducing health disparities in CKD.