# The Effect of Sleep Disorder Diagnosis on Mortality in End-Stage Renal Disease Patients
## 4 Discussion
In the case of CCI, a change in the adjusted odds ratio of \(\sim\)0.01 (i.e., aHR = 0.990 with a 95% CI of 0.989-0.991) is likely not particularly clinically important. Two of the leading causes of mortality in patients with ESRD on dialysis are cardiovascular disease and infection [32]. Sleep disorders are associated with adverse effects on blood pressure control, cardiac remodeling, and immune function, which would lead one to anticipate higher mortality rates in this population [15; 33]. One possible explanation for this finding is that patients with sleep disorders and ESRD are seeing medical professionals more often due to their dialysis. This could lead to earlier detection of complications in order that their problems are promptly worked up and treated. Additionally, OSA causes progression of CKD through a decline in renal oxygenation that can initiate and promote a fibrotic response [16; 17]. This could explain the \"wearing off\" of the protective effect of a sleep diagnosis at the 10-year mark. Sleep disorders are tightly linked with cardiac complications, such as hypertension that can worsen renal disease and increase mortality. Our study indicates that diagnosing sleep disorders may impart a survival advantage in patients with ESRD, although this study did not monitor the treatment of sleep disorders after diagnosis. The American College of Physicians recommends cognitive behavioral therapy for insomnia as a line first treatment and pharmacological intervention (benzodiazeppines and non-benzodiazeppine receptor agonists) as an adjunct or for secondary treatment of insomnia [10]. For treatment of sleep apnea in ESRD patients, conservative non-pharmacologic, such as weight loss and avoidance of some exacerbating medicines have shown limited success, but nasal continuous positive airway pressure (C-PAP) shows efficacy. Better uremic control with nocturnal hemodialysis or renal transplantation may also improve sleep apnea. RLS is associated with iron deficiency and anemia in order that high-dose iron-dextran and erythromycinropeoietin have been shown to improve the disorder. Dopamine agonists and precursors may also provide relief [13]. The observed prevalence of sleep disorders that we detected in this study is lower than what has been found in other studies of CKD [30], and it would seem that many ESRD patients with sleep disorders are not being diagnosed. Presumably, if patients with these sleep disorders are not diagnosed, their sleep disorders are not treated. Therefore, diagnosis and subsequent treatment of sleep disorders could impart a survival advantage by slowing the effects of sleep disorders on kidney function. The observed results appear to be similar to what is known as \"the obesity paradox\", where obese patients with cardiovascular disease appear to have better survival compared with CVD patients of normal weight [34]. This is an example of collider bias (or selection bias), which may explain the unexpected results in this study. A collider is a common effect of the exposure and the outcome. In this case, ESRD may be a collider, with sleep disorders (particularly OSA) as the exposure. OSA may worsen CKD, leading to progression to ESRD. Additionally, there are unmeasured confounders (such as BMI, socioeconomic status, among others) that may cause or worsen ESRD, and are associated with increased risk of death. In this case, selection of study participants with ESRD represents conditioning on a variable that acts as a collider between OSA (or other sleep disorders) and unmeasured confounders. There are significant limitations to the observed findings in this study as this was a retrospective analysis of the USRDS database, which consists of procedural and diagnostic codes from billing CMS claims in an ESRD population limited to the United States. Interpretation of these data assumes accuracy of the ICD-9 and ICD-10 codes used by both hospitals and physicians while caring for patients enrolled in the database. The absence of a diagnosis code does not rule out the presence of a sleep disorder.