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.

PUBLIC HEALTH RELEVANCE: If sleep apnea causes or worsens chronic kidney disease, then treating sleep apnea might prevent kidney disease or stop it from worsening. In this study, we will determine if people who are diagnosed with sleep apnea lose kidney function faster than people who do not have sleep apnea. We will also see if positive airway pressure (PAP) therapy for sleep apnea helps prevent kidney function loss.