Racial and Cardiovascular Risk Factor Anomalies in CKD

描述（由申请方提供）：在接受维持透析治疗的慢性肾脏疾病（CKD）患者中，非洲裔美国患者的比例显著高于非西班牙裔白色患者，并且心血管疾病的传统风险因素（如高胆固醇血症、高血压和肥胖）似乎与不良结局存在异常的负相关性。非裔美国人中终末期肾病（ESRD）的患病率异常高，这可能是由于他们的CKD发病率较高和/或CKD进展较快、死亡率较低和肾移植可能性较低等复杂相互作用的结果。ESRD中异常的心血管风险因素可能是与营养不良和炎症相关的短期竞争风险的结果，似乎不利的传统心血管风险因素与更好的营养状态相关，这可能会对非裔美国人产生不同的影响，因此为他们在ESRD中更好的生存提供了一种解释。非透析依赖性CKD分期的死亡率是否存在类似的自相矛盾的差异尚不清楚;其存在、程度、发生的CKD分期及其作用机制都需要足够详细地阐明，以便设计适当的诊断和干预策略，以降低心血管风险并缓解结局的种族差异。本着PA-09-196的精神，我们将利用从国家VA研究数据库获得的数据，该数据库是唯一一个大型管理数据库，包含美国各地大量个体（超过400万个体，包括超过50万CKD患者）的详细社会人口统计学和临床信息。我们将通过纵向研究肾小球滤过率正常的患者队列，研究CKD事件和死亡率对种族组成和心血管危险因素变化的人群动态影响。我们将使用复杂的流行病学方法，包括联合建模，以评估风险因素参数的纵向变化对死亡率的影响，以及边缘结构模型，以调整基线和时间依赖性混杂因素，探索各种社会人口统计学特征、合并症、生化指标和药物使用对死亡率和进展性CKD的影响。这个为期三年的项目将产生丰富的信息，以更可靠地检查上述假设与种族和心血管差异的患者的结果与所有水平的肾功能，可能有显着的公共卫生影响。

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.