Sleep-Disordered Breathing and Outcomes in Chronic Kidney Disease

慢性肾脏疾病（CKD）是一个日益严重的公共卫生问题，影响着美国超过2700万成年人， 包括超过70万名需要透析或移植的终末期肾病患者。的数量 ESRD流行病例继续以每年约20，000例的速度增加，估计费用超过30美元 每年10亿。尽管这个问题的严重性，我们对CKD进展的风险因素的理解是 不完整这一建议的核心科学前提是，睡眠呼吸障碍代表了一种 CKD进展的新的、潜在可改变的风险因素。尽管睡眠障碍的流行率 据估计，在CKD患者中，呼吸的影响高达50%，其对CKD进展的影响 尚未在前瞻性研究中进行系统研究。基于可靠的临床和实验室数据， 我们假设睡眠呼吸障碍通过多种途径增加CKD进展的风险， 慢性肾脏病的发病机制包括慢性肾脏病风险因素（高血压、糖尿病和肥胖）的恶化。此外，本发明还提供了一种方法， 间歇性缺氧和复氧可促进炎症、氧化应激、交感神经 系统激活和肾小管损伤。除了肾衰竭风险增加外，CKD患者 发病率和死亡率的风险过高，生活质量和身体状况较差， 功能特别重要的是，心血管事件的发生率在患有糖尿病的患者中高出2 - 5倍。 CKD与无CKD的患者比较。在非CKD人群中，睡眠与慢性肾脏病之间存在很强的相关性。 呼吸紊乱和心血管风险增加，但这种关联尚未在CKD中进行研究。 评估睡眠呼吸障碍对CKD患者心血管结局的影响具有临床意义 因为它有可能改善风险分层，并促进识别高风险亚组， 可以从筛查和治疗中获益。这项研究的总体目标是评估睡眠- 呼吸紊乱（通过家庭睡眠监测评估）作为临床的潜在非传统风险因素 和以患者为中心的结果在一个不同的队列2,200名成人轻度至中度CKD。拟议 这项研究将利用正在进行的NIDDK申办的慢性肾功能不全队列的基础设施 （CRIC）研究旨在实现以下目标1）检查睡眠呼吸障碍与 和CKD进展; 2）评估睡眠呼吸障碍作为一个独立的预测因素 CKD成人队列中心血管事件的发生率; 3）评估睡眠障碍的影响 呼吸对CKD患者中心结局的影响。由于睡眠呼吸障碍是一种可治疗的疾病， 这项研究有可能为介入治疗的设计和实施提供高质量的证据。 研究以改善这一人群的结局。

Chronic kidney disease (CKD) is a growing public health problem that affects over 27 million adults in the US, including over 700,000 with end-stage renal disease (ESRD) requiring dialysis or transplant. The number of ESRD prevalent cases continues to rise by ~20,000 cases per year, and the cost is estimated at over $30 billion per year. Despite the magnitude of this problem, our understanding of risk factors for CKD progression is incomplete. The central scientific premise for this proposal is that sleep disordered-breathing represents a novel, potentially modifiable risk factor for CKD progression. Even though the prevalence of sleep-disordered breathing has been estimated to be as high as 50% in individuals with CKD, its impact on CKD progression has not been systematically investigated in a prospective study. Based on robust clinical and laboratory data, we hypothesize that sleep disordered-breathing augments the risk CKD progression through multiple mechanisms including the exacerbation of CKD risk factors (hypertension, diabetes and obesity). In addition, intermittent hypoxia and reoxygenation may promote inflammation, oxidative stress, sympathetic nervous system activation and renal tubular injury. In addition to an increased risk for kidney failure, patients with CKD experience a disproportionately high risk of morbidity and mortality, as well as poor quality of life and physical function. Of particular significance, cardiovascular event rates are two- to five-times higher in patients with CKD compared with those without CKD. In non-CKD populations, there is a strong association between sleep- disordered breathing and increased cardiovascular risk, but this association has not been studied in CKD. Evaluating the impact of sleep-disordered breathing on cardiovascular outcomes in CKD is of clinical relevance because it has the potential to improve risk stratification and facilitate identification of high risk subgroups who may benefit from screening and treatment. The overall objective of the proposed study is to evaluate sleep- disordered breathing (assessed by home sleep monitoring) as a potential nontraditional risk factor for clinical and patient-centered outcomes in a diverse cohort of 2,200 adults with mild-to-moderate CKD. The proposed study will leverage the infrastructure of the ongoing NIDDK-sponsored Chronic Renal Insufficiency Cohort (CRIC) Study to achieve the following Aims 1) Examine the association between sleep-disordered breathing and CKD progression in adults with CKD; 2) Evaluate sleep-disordered breathing as an independent predictor of cardiovascular events within a cohort of adults with CKD; 3) Assess the impact of sleep-disordered breathing on patient-centered outcomes in CKD. Since sleep-disordered breathing is a treatable condition, this study has the potential to provide high quality evidence for the design and implementation of interventional studies to improve outcomes in this population.