Reasons for the Excess Mortality and Functional Decline in Older Adults with CKD

描述(申请人提供)：慢性肾脏疾病(CKD)的患病率和发病率，定义为估计的肾小球滤过率(EGFR)和60毫升/分钟/1.73平方米，随着年龄的增长显著增加。然而，CKD的一般管理方法是基于年轻人和中年人的证据，可能不适用于老年人。这是因为在较年轻的时候，CKD通常是一种进行性疾病，随着肾功能的恶化，患者可能会发展为终末期肾病(ESRD)，需要透析或肾移植。然而，超过90%的患有CKD的老年人死亡时没有进展到终末期肾病。虽然慢性肾脏病患者进展为终末期肾病的风险可能会随着年龄的增长而降低，但在老年人中，慢性肾脏病与死亡率的增加和日常生活能力(ADL)的下降有关，即使在对传统的心血管疾病风险因素(如高血压、高胆固醇、糖尿病)进行调整后也是如此。患有CKD的老年人也有更高的老年特有危险因素，定义为老年人中常见的情况，但传统上不被认为是CKD患者的危险因素。这些因素是综合老年评估的一部分，包括认知障碍、抑郁、跌倒、服用多种药物和身体表现不佳。老年特有的危险因素与一般老年人群中的死亡率和功能衰退有关，并可能部分解释老年CKD患者死亡率和功能衰退的部分原因。然而，关于这些因素对这一人群中超额死亡率和更高的功能减退率的贡献的数据很少。因此，我们提出以下具体目标：(1)确定老年特有因素是否可以解释老年CKD患者的超额死亡风险；(2)确定老年特有因素和较差的体能表现是否可以解释老年CKD患者较高的功能减退率。对于目标1，我们将使用中风原因和种族差异研究中7,492名70岁参与者的数据来确定每个老年人特有的风险因素在CKD和死亡率之间的关联中所占的比例。对于目标2，我们将使用来自UAB老龄化研究的400名参与者(69岁)的数据来确定每个老年人特有的风险因素和糟糕的体能表现在多大程度上占CKD和功能衰退之间的关联的比例。确定这些人群中与慢性肾脏病相关的死亡和功能衰退的额外风险的因素是实现我们改善患有慢性肾脏病的老年人的“健康跨度”的目标的广泛而必要的第一步。这种方法利用来自AGES研究和UAB衰老研究的丰富和互补的现有数据，将肾病学和衰老研究联系起来。这项拟议的研究将确定老年人特有的风险因素，这些因素将导致以患者为中心的干预措施，以降低患有CKD的老年人的死亡率和功能下降的风险。

DESCRIPTION (provided by applicant): The prevalence and incidence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2, increases markedly with age. Yet, the general approach to management of CKD is based on evidence from young and middle-aged adults and may not apply to older adults. This is because at younger ages, CKD is often a progressive disorder and as kidney function worsens patients may develop end-stage renal disease (ESRD) requiring dialysis or kidney transplant. However, over 90% of older adults with CKD die without progressing to ESRD. While the risk of progression to ESRD among patients with CKD may decrease with age, among older adults, CKD is associated with increased mortality and declines in the ability to perform activities of daily living (ADLs) even after adjustment for traditional cardiovascular disease risk factors (e.g. hypertension, high cholesterol, diabetes). Older adults with CKD also have a higher prevalence of geriatric-specific risk factors, defined as conditions that are common among older adults, but not traditionally considered risk factors in CKD patients. These factors are part of the comprehensive geriatric assessment and include cognitive impairment, depression, falls, polypharmacy and poor physical performance. Geriatric-specific risk factors are associated with mortality and functional decline in the general geriatric population and may explain part of the excess mortality and functional decline among older adults with CKD. However, there are few data on the contribution of these factors on the excess mortality and higher rate of functional decline in this population. Therefore, we propose the following specific aims (1) To determine if geriatric-specific factors explain the excess mortality risk among older adults with CKD and (2) To determine if geriatric-specific factors and poor physical performance explain the higher rate of functional decline among older adults with CKD. For Aim 1, we will use data on 7,492 participants ¿ 70 years of age in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the degree to which each geriatric-specific risk factor accounts for a proportion of the association between CKD and mortality. For Aim 2, we will use data on 400 participants ¿ 69 years of age from the UAB Study of Aging to determine the degree to which each geriatric-specific risk factor and poor physical performance accounts for a proportion of the association between CKD and functional decline. Identifying factors that explain the excess risk for mortality and functional decline associated with CKD in this population is a broad, but necessary first step to achieving our goal to improve "health span" for older adults with CKD. This approach bridges nephrology and aging research using rich and complementary existing data from the REGARDS study and the UAB Study of Aging. The proposed study will determine geriatric-specific risk factors that will lead to patient-centered interventions to reduc risks for mortality and functional decline among older adults with CKD.