Gender Disparities and Vascular Function in Chronic Kidney Disease Outcomes

描述(由申请者提供)：这项以患者为导向的研究事业发展奖(K23)的候选人是伊利诺伊大学芝加哥分校(UIC)的肾病学家、医学博士、公共卫生硕士安娜·C·里卡多。Ricardo博士的短期目标是通过开展研究，重点研究慢性肾脏疾病(CKD)中的性别差异，以及血管内皮细胞功能的性别差异对这些差异的影响，从而获得经验和发展技能。她 长期的职业目标是成为一名独立的调查员，通过生活方式干预，进行专注于减少慢性肾脏病健康不平等的研究。为了实现她的目标，里卡多博士制定了一份全面的职业发展计划，其中包括UIC公共卫生学院的指导性研究和教学课程。Ricardo博士强大的导师和合作者团队包括拥有NIH长期资助和丰富导师经验的世界级专家。她的主要导师詹姆斯·P·拉什医学博士是少数族裔人群中慢性肾脏病流行病学方面的专家；她的共同导师玛莎·L·戴维卢斯医学博士在心血管疾病流行病学方面拥有专业知识。该提案还包括一个多学科的合作者团队，他们在妇女健康领域拥有专门知识，纵向 数据分析，以及运动对血管功能的影响。里卡多博士成功地发展成为一名独立的内科科学家将得益于广泛的设施 以及UIC提供的资源，包括临床和翻译科学奖、妇女与性别研究中心和公共卫生学院。里卡多博士的研究将提升她在初级数据收集和纵向数据分析方面的技能。该提案利用了美国国立卫生研究院资助的慢性肾功能不全队列研究(CRIC)的基础设施，CRIC研究是一项针对成人慢性肾功能不全的大型和多样化的观察性研究。有证据表明，CKD中存在着与性别相关的显著差异。来自美国肾脏数据系统的数据表明，男性终末期肾脏疾病的发病率是男性的1.5倍，而国家健康和营养检查调查显示，女性慢性肾脏病的患病率更高。几项研究表明，男性CKD进展更快，但这并不是一个一致的发现。此外，以前的研究并不是为解决这个问题而设计的，而且很少涉及少数族裔。在普通人群中，有证据表明，女性和男性心血管结局的差异率可能与内皮功能的性别差异有关，这在一定程度上归因于雌激素对女性的保护作用。此外，有限的数据表明内皮功能障碍可能是CKD进展的预测指标。然而，内皮功能在CKD进展中的性别差异中的作用尚不清楚。这是一个有意义的领域，因为对非CKD人群的研究表明，通过药物治疗(例如，ACE抑制剂)或生活方式干预(例如，锻炼)，内皮功能可能会得到改善。拟议项目的具体目标是：1)在CRIC研究中检查肾脏和心血管结果的性别差异；2)在150名伊利诺伊大学CRIC研究参与者中检查内皮功能的性别差异以及内皮功能作为CKD进展预测因子的作用；以及3)评估为期12周的先导性阻力运动训练干预的可行性及其对内皮功能和心血管的影响 慢性肾脏病男性和女性的危险因素。这一职业发展奖将为里卡多博士追求致力于减少慢性肾脏病健康差距的独立研究生涯奠定基础。

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.