Sleep-Disordered Breathing and Outcomes in Chronic Kidney Disease

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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.