# The Effect of Sleep Disorder Diagnosis on Mortality in End-Stage Renal Disease Patients
## 1 Introduction  
Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide [1, 2]. CKD also affects quality of life through symptoms of uremia, volume overload, and worsened fatigue. Changes in quality of life are especially evident once renal replacement therapy is initiated. CKD treatment is costly due to the expensive nature of renal replacement therapies including dialysis and transplant [2, 3]. In the United States, annual Medicare spending on CKD and end-stage renal disease (ESRD) is more than USD 98 billion [4].  
CKD has been linked to increased cardiovascular disease (CVD) risk and mortality as well as all-cause mortality [5]. Traditional cardiovascular risk factors, such as diabetes, hypertension, hyperlipidemia, and smoking do not completely explain this increased risk [6]. One hypothesized explanation for this discrepancy is that non-traditional risk factors, such as sleep disorders may increase mortality [5, 7]. Compared to the general public, patients with CKD are reported to have a higher incidence of sleep disordersincluding obstructive sleep apnea (OSA), insomnia, restless leg syndrome (RLS), and hypersomnia [8; 9]. In fact, estimates of the prevalence of sleep disorders, based largely on questionnaires of patients on dialysis, range from 40 to 85% [10]; however, a recent study used actigraphy to monitor sleep in 64 dialysis patients versus matched healthy controls and also found a higher prevalence of poor quality sleep in the ESRD patients versus the controls (59% versus 13% in terms of sleep efficiency and 81% versus 34% for sleep fragmentation) [11]. Unfortunately, most ESRD patients with sleep difficulty receive no treatment [10].  
OSA is common in patients with CKD and increases as kidney function declines [12; 13]. OSA is characteristically associated with nocturnal hypoxemia which can lead to worsening the glomerular filtration rate (GFR) and accelerate the progression of CKD [14; 15]. It is thought that through chronic, intermittent, nocturnal hypoxemia the decline in renal oxygenation can initiate and promote a fibrotic response [16; 17]. While OSA contributes to the progression of CKD, there is also evidence that declining kidney function contributes to the pathogenesis of sleep disorders, such as OSA. Volume overload causes congestion of the upper airways which causes OSA due to swelling of the tissues [18]. Furthermore, accumulation of uremic toxins induces metabolic acidosis and hypocaponia and increases chemosensitivity to carbon dioxide, leading predominantly to central sleep apnea (CSA) [18]. Indeed, sleep apnea is estimated to occur in more than 50% of ESRD patients compared to 2-4% in the general population [13]. Uremia is also associated with restless leg syndrome (RLS) and affects between 12% and 57% of patients on dialysis [19; 20]. RLS symptoms in dialysis are severe and have a negative impact on quality of life and are thought to increase the risk of mortality in this population [11]. Periodic limb movements during sleep induce rises in blood pressure, which may play a role in the pathogenesis of cardiovascular diseases [21].  
The relationship between sleep disorders and mortality has not been studied in ESRD patients. This study is a retrospective analysis of the United States Renal Data System (USRDS) database to determine whether there is worsened mortality in those with a sleep disorder diagnosis.