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

描述（由申请人提供）：慢性肾脏病（CKD）的患病率和发病率（定义为估计肾小球滤过率（eGFR）<60 ml/min/1.73 m2）随年龄显著增加。然而，CKD管理的一般方法是基于年轻人和中年人的证据，可能不适用于老年人。这是因为在年轻时，CKD通常是一种进行性疾病，随着肾功能的下降，患者可能会发展为需要透析或肾移植的终末期肾病（ESRD）。然而，超过90%的CKD老年人在没有进展为ESRD的情况下死亡。虽然CKD患者进展为ESRD的风险可能会随着年龄的增长而降低，但在老年人中，即使在调整传统心血管疾病风险因素（例如高血压、高胆固醇、糖尿病）后，CKD仍与死亡率增加和日常生活活动（ADL）能力下降相关。老年CKD患者也有较高的老年特异性风险因素患病率，定义为老年人中常见的疾病，但传统上不认为是CKD患者的风险因素。这些因素是综合老年评估的一部分，包括认知障碍、抑郁、福尔斯、多种药物和身体表现差。老年特异性风险因素与一般老年人群的死亡率和功能下降相关，并可能解释CKD老年人死亡率过高和功能下降的部分原因。然而，关于这些因素对这一人群的过度死亡率和较高的功能衰退率的影响的数据很少。因此，我们提出了以下具体目标：（1）确定老年特异性因素是否可以解释CKD老年人的过度死亡风险;（2）确定老年特异性因素和身体表现差是否可以解释CKD老年人功能下降的较高发生率。对于目标1，我们将使用卒中地理和种族差异的原因（REGARDS）研究中7，492名70岁以上参与者的数据，以确定每个老年特异性风险因素在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69岁参与者的数据，以确定每个老年特异性风险因素和身体表现差在CKD和功能下降之间的关联中所占的比例。确定解释该人群中与CKD相关的死亡率和功能下降的过度风险的因素是实现我们改善CKD老年人"健康寿命"目标的广泛但必要的第一步。这种方法使用来自REGARDS研究和UAB衰老研究的丰富和互补的现有数据，将肾脏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，从而采取以患者为中心的干预措施，以降低患有慢性肾病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.