**6. Pathogenesis-figure 2**

Sleep apnea in patients with ESRD is mostly obstructive but several observers have reported features of both obstructive and central sleep apnea (16,31). Sleep apnea is caused by both impaired central ventilatory control and upper air way occlusion during sleep. Enhanced ventilatory sensitivity to hypercapnea correlates with apnea severity (22). Conversion from conventional Hemodialysis (CHD) to nocturnal Hemodialysis (NHD) has been associated with reduced severity of sleep apnea due to reduction in ventilatory sensitivity to hypercapnea(31). Upper airway occlusion can be caused by fluid overload and interstitial edema in the upper air way (23). Displacement of fluids from the lower limbs increases neck circumference and pharyngeal resistance and reduces upper air way cross sectional area, contributing to the pathogenesis of obstructive sleep apnea (OSA). Pharyngeal cross sectional area in patients on CHD was smaller than the control, suggesting that this may predispose to upper airway occlusion during sleep (22). Conversion from CHD to NHD is associated with an increase in pharyngeal cross sectional area, possibly due to improve fluid removal(31). Conversion from continuous ambulatory peritoneal dialysis (CAPD) to nocturnal peritoneal dialysis has been shown to reduce the frequency of sleep apnea (24). Upper airway dilator muscle dysfunction due to neuropathy or myopathy associated with chronic uremia or the underlying cause of renal disease such as diabetes mellitus can cause narrowing of pharyngeal muscles (31). There could also be some role for oxidative stress, inflammatory cytokines and middle molecules, all elevated in ESRD in the development of ventilatory instability and or upper airway occlusion, but this has not been established (66).

The apnea –hypopnea index (AHI) is an index used to assess the severity of sleep apnea based on the total number of complete cessations (apnea) and partial obstructions (hypopnea) of breathing occurring per hour of sleep found during polysomnography. Patients with advanced CKD not on dialysis who are non-diabetic are predisposed to more severe AHI as compared to patients with less advanced CKD (25). In patients with diabetes no such association was found probably due to the fact that diabetes itself may be an

Sleep Disorders Associated with Chronic Kidney Disease 389

questionnaire with 8 questions and is more commonly used. It provides a measure of a person's general level of daytime sleepiness, or their average sleep propensity in daily life .The ESS asks people to rate, on a 4-point scale (0 – 3), their usual chances of dozing off or falling asleep in 8 different situations or activities that most people engage in as part of their daily lives. The total ESS score is the sum of 8 item-scores and can range between 0 and 24.The higher the score, the higher the person's level of daytime sleepiness. Most people can

Although the characteristic features of sleep apnea may be absent, a history of snoring, witnessed apnea during sleep, and day time sleepiness are suggestive of sleep apnea. Objective diagnostic testing includes home ambulatory monitoring which records air flow,

Polysomnography (PSG), also known as a sleep study is a nocturnal, laboratory- test used in the diagnosis of Sleep Apnea Syndrome (SAS). It is often considered the standard for diagnosing OSAS, determining the severity of the disease, and evaluating various other sleep disorders that can exist with or without OSAS. PSG consists of a simultaneous recording of multiple physiologic parameters related to sleep and wakefulness. It generally includes monitoring of the patient's airflow through the nose and mouth, blood pressure, heartbeat as measured by an electrocardiograph, blood oxygen level,EEG wave patterns, eye

Polysomnography can be performed in a sleep laboratory or center and includes comprehensive monitoring of respiration, sleep stages and leg movements. Polysomnography is used to quantify the Apnea-Hypopnea Index (AHI). AHI is an index used to assess the severity of sleep apnea based on the total number of complete cessations (apnea) and partial obstructions (hypopnea) of breathing occurring per hour of sleep. These pauses in breathing must last for at least 10 seconds and be associated with a 3% or greater decrease in oxygenation of the blood. To determine AHI, add the total number of apnea events, plus hypopnea events and divide by the total number of minutes of actual sleep

In general, the AHI can be used to classify the severity of disease (mild 5-15, moderate 16-30,

Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT) can be considered for the evaluation of day time sleepiness. MSLT is used to measure the time elapsed from the start of a daytime nap period to the first signs of sleep, called sleep latency. The test is based on the idea that the sleepier people are, the faster they will fall asleep. The MWT is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during sleep conducive circumstances. The test isolates a person from factors that can influence sleep such as temperature, light, and noise. Furthermore, the patient is also advised to not take any hypnotics, drink alcohol, or smoke before or during the test. After allowing the patient to lie down on the bed, the time between lying down and falling asleep is measured and used to determine one's daytime sleepiness.

answer the ESS, without assistance, in 2 or 3 minutes. (www.sleepfoundation.org).

movements(EOG), and the movements of respiratory muscles and limbs(EMG).

Apnea + Hypopnea divided by actual sleep time, then multiply by 60

snoring, respiratory movement, oxygen saturation, and heart rate.

time, then multiply by 60.For example:

and severe greater than 30).

200 apneas, 200 Hypopneas (400 Total Events) 420 Minutes Actual Sleep Time (7 hours x 60) Divide 400 by 420 = .95 x 60 = 57 AHI (Severe OSA)

Fig. 2. Pathogenesis of sleep Apnea Syndrome (SAS).

overriding factor for the development of sleep apnea (25). It was also found that AHI index correlated weakly with urea level in all patients, but not with creatinine clearance.

Obesity is not required for ESRD patients to develop sleep apnea. Snoring is less intense in patients with CKD who have sleep apnea than in patients with sleep apnea with normal renal function (67).
