Sleep Apnea, PAP Therapy, and Kidney Function Trajectory

描述(由申请人提供)：这项研究的目的是确定睡眠呼吸暂停是否是慢性肾脏疾病(CKD)的一种新的、可改变的危险因素。我们建议对现有数据集进行研究，以帮助确定被诊断为睡眠呼吸暂停的患者的肾功能丧失是否加速，以及睡眠呼吸暂停的正压(PAP)治疗是否降低了肾功能丧失的比率。我们将通过使用两个丰富和互补的数据集：威斯康星州睡眠队列和南加州凯撒永久人口研究数据库进行纵向分析来实现这些目标。睡眠呼吸暂停是影响五分之一美国人的常见疾病，可以通过PAP疗法有效地治疗。睡眠呼吸暂停与慢性肾脏病的风险特征相似，包括高血压和糖尿病，这是终末期肾病(ESKD)的两个最常见的原因。众所周知，睡眠呼吸暂停对心血管、中枢神经和内分泌系统有害。睡眠呼吸暂停与慢性肾脏病的关系尚不清楚。我们假设，在后来被诊断为呼吸暂停的人和患有更严重的睡眠呼吸暂停的人中，观察到肾功能丧失的速度更快。我们假设，PAP治疗将减缓肾功能丧失，有效的PAP治疗将比无效治疗更大程度地减缓肾功能丧失。 威斯康星州睡眠队列研究(WSCS)是由美国国立卫生研究院资助的一项为期20年的前瞻性研究，对1,522名中年健康成年人进行研究，定期使用金标准测量方法、PAP治疗充分性测量方法以及可用于评估肾功能的系列血清肌酐测试来评估睡眠呼吸暂停的严重程度。KPSC人口研究数据库包含100,000多名睡眠呼吸暂停患者的有效病例识别，包括诊断和PAP设备分配日期，以及包括临床获得的血清肌酐测试在内的完整电子医疗记录。在这两个队列中，肾功能将基于估计的肾小球滤过率(EGFR)进行评估。我们将使用线性斜率和非线性混合模型对EGFR轨迹进行建模，以比较PAP治疗前后的EGFR趋势。在每个队列中，将建立一个非呼吸暂停对照组，并对主要并发症进行控制。我们打算通过这项研究直接为未来的有效性试验提供信息。 在KPSC等大量人群中，利用主动和被动数据收集，在干预和非干预地点对睡眠呼吸暂停的筛查和治疗进行了比较。这项研究的结果有可能推动一个有希望的研究领域，最终可能改变对高肾脏风险患者或已确定的CKD患者的评估和治疗，以帮助预防相关的发病率和死亡率。

DESCRIPTION (provided by applicant): The purpose of this study is to determine if sleep apnea is a novel, modifiable risk factor for chronic kidney disease (CKD). We propose a study of existing data sets to help determine if kidney function loss is accelerated in patients who are diagnosed with sleep apnea, and if positive airway pressure (PAP) therapy for sleep apnea reduces the rate of kidney function loss. We will accomplish these aims through longitudinal analyses using two rich and complementary data sets: the Wisconsin Sleep Cohort and Kaiser Permanente Southern California (KPSC) Population Research Databases. Sleep apnea is common disorder affecting 1 in 5 Americans and can be effectively treated using PAP therapy. Sleep apnea shares a similar risk profile to CKD, including hypertension and diabetes, the two most common causes of end-stage kidney disease (ESKD). Sleep apnea is known to be deleterious to the cardiovascular, central nervous and endocrine systems. The relationship of sleep apnea to CKD is not yet clear. We hypothesize that a faster rate of kidney function loss will be observed in individuals who are later diagnosed with apnea and in individuals with more severe sleep apnea. We hypothesize that PAP therapy will slow kidney function loss and that effective PAP therapy will slow kidney function loss to a greater degree than ineffective therapy. The Wisconsin Sleep Cohort Study (WSCS) is 20-year ongoing NIH-funded prospective study of 1,522 middle-aged healthy adults with periodic assessments of sleep apnea severity using gold-standard measures, measures of PAP therapy adequacy, and serial serum creatinine tests from which kidney function may be estimated. The KPSC Population Research Databases contain validated case-identification of over 100,000 sleep apnea patients, including diagnosis and PAP device dispensation dates, and complete electronic medical records that include clinically obtained serum creatinine tests. In both cohorts, kidney function will be assessed based on the estimated glomerular filtration rate (eGFR). We will model eGFR trajectory using linear slopes and non-linear mixed models to compare eGFR trend before and after PAP therapy. In each cohort, a non- apnea comparison group will be constructed and major comorbidities will be controlled. We intend this study to directly inform the conduct of a future effectiveness trial in which screening and therapy for sleep apnea is compared across intervention and non-intervention sites utilizing active and passive data collection in a large population, such as KPSC. The results of this study have the potential to push forward a promising area of research that eventually may alter the evaluation and treatment of patients at high renal risk or with established CKD to help prevent related morbidity and mortality.