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JNEPHROL 2009; 22: 318-325

Sleep disturbances and sleep apnea in patients on chronic peritoneal dialysis

Sydney C.W. Tang, Kar Neng Lai
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong - China

AbstrAct
Sleep disturbances in chronic peritoneal dialysis (PD) patients are increasingly widely recognized. These include changes in sleep architecture, sleep apnea syndrome, restless legs syndrome, periodic limb movement disorder and excessive daytime sleepiness. Some of these entities will be addressed in this review. The study tools for detecting sleep-related disorders in PD patients range from self-reported questionnaires (subjective) to standard overnight polysomnographic measurements (objective). Both these tools identify a high prevalence (over 50%) of sleep-related disorders among dialysis patients. Among these, sleep apnea syndrome is one of the most widely reported sleeprelated disorders in PD. Sleep apnea in PD may be attributed to chronic fluid overload and uremia, leading to both obstructive and central forms of apneas. The exact underlying pathophysiology, however, is complex and likely involves a combination of multiple factors. There are preliminary data that nocturnal PD may be advantageous over conventional continuous ambulatory peritoneal dialysis in correcting sleep apnea associated with PD. Randomized studies are needed for confirmation. Key words: Peritoneal dialysis, Polysomnography,

sleep-related complaints became increasingly recognized and are characterized by difficulty initiating and maintaining sleep, problems with restless, jerking legs, and daytime sleepiness. Indeed, sleep problems, and in particular insomnia, are among the most disturbing symptoms experienced by this group of patients and are consistently cited as major sources of stress and as factors negatively impacting upon quality of life (2). Similar to the general population, increased stress, anxiety, depression and worry are also associated with poor subjective sleep quality in dialysis patients (3). It is now widely accepted that sleep disturbances in dialysis patients comprise a constellation of disrupted sleep architecture, sleep apnea syndrome, restless legs syndrome (RLS), periodic limb movement disorder (PLMD) and excessive daytime sleepiness (4, 5). In this article, we review the current knowledge on sleep disturbances and in particular sleep apnea in chronic peritoneal dialysis patients.

Investigational tools
Understandably, the early tools used to gauge sleep disturbances were based on self-reported complaints. Later, structured questionnaires were available to standardize the measured parameters and for gauging their severity. Symptoms of fatigue and excessive daytime sleepiness (EDS) are common complaints in sleep clinics. EDS is defined as the inability to stay awake and alert during the major waking episodes of the day, when an individual would usually be expected to be alert (6). Several methods have been used to measure sleepiness subjectively, including self-assessment tools such as the Stanford Sleepiness Scale and the Epworth Sleepiness Scale (ESS) (7). Multiple regression analysis showed that ESS scores were more closely related to the frequency of apneas than to the degree of hypoxemia in obstructive sleep apnea (OSA). ESS scores give a useful measure of average sleep propensity. In the realm of sleep medicine, the ESS is frequently used, and it focuses on self-reported

Questionnaire, Restless legs, Sleep, Sleep apnea

IntroductIon
Sleep disturbances are highly prevalent among dialysis patients. One of the earliest reports of subjective sleeprelated complaints in dialysis patients was described in 1982 by Strub et al (1), who found 14 out of 22 patients who complained of diminished, fragmented sleep and increased time lying awake in bed. In subsequent years,
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Fig. 1 - Central sleep apnea: In this 1-minute polysomnography (PSG) tracing, there was absence of airflow and thoracic and abdominal movements altogether for over 20 seconds, associated with oxygen desaturation from 98% to a nadir of 92%. Upon gradual resumption of breathing, there were synchronous thoracic and abdominal movements, which were not preceded by snoring, as shown by an absence of any signal in the microphone (MICRO).

behavior and more recently has been used to reflect the likelihood of sleep apnea. For the ESS, subjects rate the likelihood of falling asleep in 8 scenarios with various levels of stimulation (Tab. I), on a scale of 0 (not at all likely) to 3 (very likely). Patients with ESS >9 are considered to have excessive daytime sleepiness and deserve further investigation.

Fig. 2 - Obstructive sleep apnea: In this 2-minute polysomnography (PSG) tracing, there was reduction of the amplitude of airflow by more than 50% for over 10 seconds (arrow) together with oxygen desaturation from 97% to 93%, indicating hypopnea. There was synchronous breathing during normal airflow, but paradoxical breathing (opposite thoracic and abdominal movements) during hypopnea (dotted lines), indicating an obstructive component. The event was aborted by an arousal with snoring detected by the microphone (MICRO) that indicated a heightened inspiratory effort to overcome the obstruction.

TABLE I EPWORTH SLEEPINESS SCALE: SUBJECTS RATE THE LIKELIHOOD OF FALLING ASLEEP IN 8 SCENARIOS (1) Sitting and reading (2) Watching TV (3) Sitting, inactive in a public place (e.g., a theatre or a meeting) (4) As a passenger in a car for an hour without a break (5) Lying down to rest in the afternoon when circumstances permit (6) Sitting and talking to someone (7) Sitting quietly after a lunch without alcohol (8) In a car, while stopped for a few minutes in the traffic
Subjects rate the likelihood of falling asleep in these 8 scenarios with various levels of stimulation, on a scale of 0 (not at all likely) to 3 (very likely) (source (6)).

Objective measures of EDS and of sleep-disordered breathing have also been developed. These included pupillometry, performance-based tasks, the Multiple Sleep Latency Test (MSLT), overnight pulse oximetry and polysomnography (PSG). For the purpose of this review, we will only focus on overnight PSG. For the dialysis physician, it is important to understand the basic design of the PSG instrument and several basic terms in sleep medicine. Comprehensive overnight PSG typically comprises an electroencephalogram (EEG), electrooculogram (EOG), submental electromyogram (EMG), bilateral anterior tibial EMG, electrocardiogram (ECG), inductance plethysmographic measurement of chest and abdominal wall movement (respiratory effort), nasal pressure transducer detection of airflow and finger pulse oximetry. Apnea is defined as the cessation of airflow for >10 seconds during sleep, and hypopnea is defined as a reduction of airflow of 50% for >10 seconds plus an oxygen desaturation of 4% (Fig. 1) during sleep (8). Furthermore, apnea is classified as central if there is no chest and abdominal movement (Fig. 1), as obstructive if they move paradoxically (Fig. 2), and as mixed if an initial absence of ventilatory effort is followed by an obstructive apnea pattern upon resumption of effort (Fig. 3). The average number of episodes of apnea and hypopnea per hour of sleep, often referred to as the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI), is the accepted quantitative gauge of the severity of sleep apnea.
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Fig. 3 - Mixed apnea: In the 2-minute polysomnography (PSG) tracing, central sleep apnea events were terminated by several obstructive breaths. Note the presence of snoring (arrows) prior to each resumption of respiratory effort.

AHIs above 5 and 15 indicate significant and severe sleep apnea, respectively, in the general population. CheyneStokes respiration (Fig. 4) was defined as an episode of central apnea (or hypopnea) alternating with breathing that had a pattern of cyclical crescendo and decrescendo amplitude for at least 3 cycles of not less than 60 seconds each. Periodic leg movements were defined as 4 or more involuntary leg movements during sleep, each lasting 0.5 to 5.0 seconds, with 5 to 90 seconds between movements.

Fig. 4 - Cheynes-Stokes breathing: In this 5-minute polysomnography (PSG) tracing, there is an alternating pattern of crescendo and decrescendo breathing, and thoracic and abdominal movements with intervening periods of cessation of chest movement, associated with a drop in oxygen saturation. Cheynes-Stokes breathing, also called periodic breathing, is considered a form of central sleep apnea, and is associated heart failure or cerebrovascular disease (e.g., stroke), and is prevalent in dialysis patients.

Self-reported sleep disturbances using questionnaire-based assessment

A commonly used research tool to investigate sleep-related problems in the dialysis population is self-reported questionnaires. This is because the use of neurophysiological measures that are mandatory in diagnosing and characterizing some sleep-related problems, such as sleep apnea syndrome, is not readily available to or acceptable by all dialysis patients (5). It must be cautioned that the sleep questionnaire is mainly a subjective and semiquantitative tool, and is subject to high inter- and intra-personal variation due to differences in perception among individuals and within the same individual over time. Nevertheless, they are simple to administer and have been readily used to assess sleep-related problems. Walker et al (9) distributed a sleep questionnaire to 64 hemodialysis patients, and noted that among 54 patients who had responded, 83.3% had sleepwake complaints, two thirds had daytime sleepiness and a third had RLS. Similar observations were made in the peritoneal dialysis (PD) population. Among 201 continuous
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ambulatory peritoneal dialysis (CAPD) patients who completed sleep questionnaires translated into Chinese, Hui et al (10) confirmed a high prevalence of daytime sleepiness (77%), insomnia (73%) and RLS (62%). Likewise, among a cohort of 179 CAPD patients with self-reported sleep disorders, difficulty falling asleep was the most frequent complaint (74.5%), followed by frequent awakening (68%) and early morning waking (68%) (11). In addition, Lui et al (11) noted that 3 personality traits (anxiety, worry and sadness) and 2 somatic symptoms (bone pain and arthralgia) were significantly associated with sleep disorders. This underlies the importance of psychosomatic factors on sleep disorders among CAPD patients. In line with these reports, Yang et al (12) examined the association between quality of sleep and psychosocial factors in 190 PD patients using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and found a high prevalence (86%) of poor sleep in PD patients, and a strong association between quality of sleep and a number of psychosocial factors including depression, marital status, educational level and perception of quality of life. A caveat of the observation is the lack of correlation with PSG, which is the gold standard for an objective and quantitative analysis of changes in sleep architecture, sleep apnea syndrome and periodic limb movement disorder. Of these attributes, sleep-disordered breathing is noted to be highly prevalent (55%-100%) in CAPD patients (13), and more important-

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ly in the present context, sleep apnea is also associated with depression and anxiety (14). Indeed, recent data also suggested an association between sleep difficulty and impaired cognitive function, in which depressed mood predicted reduced cognitive function, whereas higher educational level predicted the reverse in incident dialysis patients (15). Therefore, there appears to be common ground for psychosocial and cognitive factors in association with sleep quality. Increased understanding of links among sleep quality, psychosocial attributes and cognitive function could benefit multiple dimensions of dialysis patients quality of life and daily functioning. Further studies are needed in this respect.

Sleep apnea syndrome

There is an overall paucity of PSG data in the studies in the literature that examine the prevalence and severity of sleep apnea in PD patients. This is partly due to the inconvenience of PSG examination, which in most instances needs to be conducted in a sleep laboratory, and partly due to limited patients tolerability of this tedious investigation, not to mention the fact that PD patients need to perform PD fluid exchange (or connection to automated cycler) before bedtime. Additionally, the labor cost of the entire PSG procedure (assembling and disassembling of multiple recording channels) and the subsequent manual scoring that is required to yield meaningful results are undoubtedly substantial. Hence, the compliance rate is in general modest, and the availability is also limited. For example, Stepanski et al (14) only managed to obtain PSG findings from 18 of 81 CAPD patients who participated in a sleep questionnaire study, and found that 11 patients (61%) had clinically significant sleep apnea. Even among PD patients who complained of chronic sleep disturbance and requested sedatives, only about 70% agreed to undergo PSG, and among them, 55% had sleep apnea (16). Rodriguez et al (17) reported that 100% of 18 CAPD patients had an AHI above 5. In our series of 46 PD patients who had undergone PSG, 89% had an AHI above 5 (18). In another cohort of 40 PD subjects who only underwent overnight pulse oximetry screening, 23 patients (58%) had sleep apnea as reflected by 4% or greater oxygen desaturation for >5 episodes/hour, or a mean nocturnal saturation <95% (19). These prevalence rates are certainly alarming considering that the corresponding rate in the middle-aged general population only ranges from 2% to 4% (20). Why is sleep apnea so prevalent in dialysis patients? The high frequency of sleep apnea in renal failure is in part explained by the fact that the most common comorbid condi-

Fig. 5 - Absolute peritoneal solute clearance during sleep in a cohort of 38 peritoneal dialysis (PD) patients who underwent sequential nocturnal PD (NPD) and continuous ambulatory peritoneal dialysis (CAPD). Kt/V and creatinine clearance (CrCl) derived from the overnight effluent during NPD or CAPD for each patient was computed. Stippled and hatched bars represent overnight pKt/V and pCrCl, respectively. pCrCl = peritoneal creatinine clearance; pKt/V = peritoneal Kt/V.

tions of renal failure, namely atherosclerosis and diabetes, are also independently associated with this syndrome. Despite the confounding effect of preexisting cardiovascular disease, several lines of evidence suggest that uremia per se is associated with sleep apnea and that this disturbance plays a major role in disrupting sleep in dialysis patients. First, the improvement of sleep apnea and restoration of autonomic modulation of heart rate related to the correction of sleep apnea by nocturnal hemodialysis (21, 22) forms the basis of sleep apnea due to uremia. Second, dialysis patients had a fourfold increase in developing sleep apnea and severe nocturnal hypoxemia after adjusting for the presence of cardiovascular disease and diabetes when compared with participants from the Sleep Heart Health Study matched for age, sex, race and body mass index (23). Third, sporadic observations that sleep apnea is at least partly reversible after renal transplant (24) lend support to the notion that sleep apnea is a direct consequence of renal failure, although more recent data failed to reproduce these results (25). Finally, our recent data (26) showed that the rate of uremic toxin removal has a bearing on the severity of central sleep apnea in PD patients: among a cohort of 38 incident patients who underwent sequential nocturnal PD (NPD) and CAPD, central sleep apnea was significantly less severe in the NPD group, which also demonstrated higher nightly Kt/V and creatinine clearance (CrCl) (Fig. 5). There were significant negative correlations between peritoneal Kt/V and AHI, and between peritoneal CrCl and AHI. The difference in overnight pKt/V or pCrCl between each mode of PD was significantly correlated with the difference in AHI
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Fig. 6A, B - Correlation between the difference in overnight pKt/V (A) or pCrCl (B) and the change in AHI following conversion from nocturnal peritoneal dialysis (NPD) to continuous ambulatory peritoneal dialysis (CAPD) in a cohort of 38 PD patients. AHI = apnea-hypopnea index; pCrCl = peritoneal creatinine clearance; pKt/V = peritoneal Kt/V.

for each individual patient (Fig. 6). Apart from uremia, the role of volume overload in causing upper airway edema and hence obstruction and sleep apnea should not be overlooked. This is reflected by the observation that the obstructive pattern was the most frequent type of apnea in PD patients and that there is a corrective potential for NPD in alleviating sleep apnea in CAPD patients (18). In the first phase of this study, overnight PSG was performed in 23 NPD subjects and in stable prevalent CAPD patients matched for demographic characteristics, comorbid conditions, peritoneal transport properties, body mass index and dialysis adequacy. Significantly more CAPD than NPD patients had sleep apnea (91% vs. 52%). The mean AHI was also higher in the CAPD group (50.9 vs. 31.6, p=0.025). In the second phase, PSG was performed in 24 incident patients while they were on intermittent NPD awaiting CAPD training, and repeated in the same subjects after they were established on stable CAPD. The prevalence of sleep apnea was significantly lower during NPD than CAPD. Mean AHI was 3.4 during NPD and 14.0 during CAPD (p<0.001). Bioelectrical impedance analysis revealed that total body water (TBW) content was significantly lower during NPD than CAPD (32.8 L vs. 35.1 L; p=0.004). The decline in TBW and hydration fraction (percentage wateronly body mass) during sleep while patients were on NPD exceeded that while on CAPD (declines of 2.81 L vs. 1.34 L; p=0.015; and 3.63% vs. 0.71%; p=0.005). Thus, NPD provides better time-averaged volume control than CAPD during sleep, and alleviates airway edema in the supine position, which in turn could lead to a lower prevalence and reduced severity of sleep apnea in PD patients. The impor322

tance of even subtle fluid shifts in sleep apnea is supported by the observation of increased pharyngeal resistance in healthy subjects in whom lower limb positive pressures were applied in the recumbent position to mimic fluid overload during sleep (27). Longer term observation is needed to address the issue of survival with NPD versus CAPD. The two studies mentioned above, however, only afforded circumstantial evidence that fluid status and shifts to the upper airway during recumbency promote sleep apnea. A direct proof of whether a reduction in TBW content would alleviate airway occlusion is provided by our recent observation (26) using magnetic resonance imaging (MRI) of the upper airway to detect any subtle changes in the airway during each of the 2 modes of PD. Volumetric MRI is a powerful tool to study anatomic changes in the upper airway and surrounding soft-tissue structures and is sensitive enough to detect changes in these structures (28). It is also a suitable tool for airway evaluation in OSA (29). One practical disadvantage of MRI is patient-perceived discomfort and claustrophobia. Among patients who underwent MRI during NPD and CAPD, there were reduced aggregate pharyngeal volumes and minimal pharyngeal cross-sectional area, together with concomitant increase in tongue volume after switching from NPD to CAPD. Tongue enlargement may also represent fluid accumulation in other soft tissues bordering the airway such as the nuchal and peripharyngeal areas which are difficult to assess in an objective manner due to the lack of clear-cut anatomic demarcations. It is conceivable that such anatomic alterations favoring narrowing of the upper airway may give rise to OSA during sleep in predisposed patients when there is a reduced tone

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Fig. 7 - Postulated pathophysiological pathways leading to sleep apnea in chronic renal failure. Volume overloaded status causes redistribution of body water during the recumbent posture and gives rise to upper airway congestion as evidenced by reduced pharyngeal luminal volumes, pharyngeal narrowing and tongue enlargement, leading predominantly to obstructive sleep apnea. Accumulation of uremic toxins induces metabolic acidosis and hypocapnia and increases chemosensitivity to carbon dioxide, leading predominantly to central sleep apnea. Other comorbid conditions and body habitus also play an adjuvant role. Nocturnal dialysis or renal transplant may alleviate volume and uremic burdens and hence improve sleep apnea. Solid arrows, enhancing effect; dashed arrows, inhibitory effect. NHD = nocturnal hemodialysis; NPD = nocturnal peritoneal dialysis; RTx = renal transplant.

Comorbid conditions such as cardiovascular disease, diabetes mellitus, obesity and other factors (see text)

of the supporting musculature of the airway. Furthermore, it is envisaged that fluid accumulation in the upper airway will increase airflow resistance of the pharynx, as reflected by the decrease in minimal pharyngeal cross-sectional area upon switching to CAPD. In support of this notion, Beecroft et al (30) recently showed that pharyngeal narrowing contributes to the pathogenesis of OSA in dialysis-dependent patients. Finally, in patients converted from conventional to nocturnal hemodialysis, there was an increase in pharyngeal size, together with improvement in sleep apnea (31).

Restless legs syndrome and periodic leg movement disorder

Jerky leg movements are frequent complaints among PD patients. Indeed, RLS and PLMD are commonly observed in PD patients. RLS is a sensorimotor movement disorder characterized by the irresistible desire to move, associated with discomfort and paraesthesias. Its diagnosis is based on history with standardized clinical criteria defined by the International RLS Study Group (32) as an urge to move the legs, beginning or worsening during periods of rest such as sitting or lying, with unpleasant leg sensations that are relieved by movement, and this urge is usually worse at night than during the day. PLMD are sudden, repetitive and highly stereotyped jerking leg movements occurring exclusively during sleep. Hence, cases of PLMD are identified during sleep laboratory investigations. The prevalence of RLS in the general population lies between 5% and 15%, with approximately 80% of patients with RLS also having PLMD (33). RLS has been reported to affect almost 30% of Caucasians undergoing dialysis (5). However, the prevalence of RLS and PLMD in the dialysis population has not been well documented, as current studies are scarce and have been limited by small sample size with the use of nonstandardized diagnostic criteria. Nevertheless, RLS has

been associated with poor quality of life, neuropsychiatric symptoms, diminished cognition and poor attention among dialysis patients (34). In addition to diminished quality of life, RLS has been associated with increased mortality in endstage renal disease (ESRD) patients. Among incident PD patients from the CHOICE cohort (35), severe symptoms of restless legs were associated with shorter survival. Similar to the unique clinical features of sleep apnea syndrome in ESRD, established nonuremic risk factors such as the age and sex of the patient are not often associated with the development of RLS in uremia. In addition, pharmacological cointerventions may also affect prevalence rates of RLS and PLMD. As a result, the reported prevalence of this syndrome in uremia has ranged between 6.6% and 83%. The pathophysiology of RLS and PLMD in uremia remains unknown. The corrective potential of kidney transplantation on RLS symptoms supports the involvement of uremia in this disturbance (5). The potential risk factors that have been put forward include anemia, iron deficiency, dialysis vintage, calcium/phosphate imbalance and peripheral and central nervous system abnormalities. As iron is a cofactor involved in the production of dopamine in the niagrostriatal areas of the brain, iron deficiency has long been associated with the development of RLS in the general population (35). However, there are no concrete data on whether this might be the case in dialysis patients. There was 1 report showing high-dose iron dextran may improve RLS/PLMD in ESRD patients, but there were only 11 patients in the treatment group versus 14 given placebo. More studies are needed to better define the prevalence, pathophysiology, impact and treatment of RLS and PLMD in PD patients.

conclusIon
PD patients have a high prevalence of sleep disorders. The pathophysiology is complex and likely involves a combination
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of factors (Fig. 7) such as dialysis adequacy, fluid balance, anemia, cardiovascular status, comorbidities, medications, body physique, psychosocial factors and demographic and lifestyle variations. Treatment using nocturnal noninvasive positive airway pressure support is beyond the scope of this review. Manipulation of uremia control and its influence on sleep disorders will likely redefine our therapeutic target for renal replacement therapy in the future. It is the role of the dialysis physician to recognize and identify the nature of the underlying sleep disturbance using the appropriate investigational tool, apply PSG examination with a low threshold, look out for subtle underdialysis and fluid overload, and take into account psychosocial and cognitive backgrounds.

Financial support: This work was supported by the Seed Funding Programme for Basic Research of the University of Hong Kong, the L & T Charitable Foundation and the House of INDOCAFE.. Conflict of interest statement: None declared.

Address for correspondence: Sydney C.W. Tang, MD, PhD Department of Medicine The University of Hong Kong Queen Mary Hospital 102 Pokfulam Road Hong Kong, PR China scwtang@hkucc.hku.hk

references
1. Strub B, Schneider-Helmert D, Gnirss F, Blumberg A. [Sleep disorders in patients with chronic renal insufficiency in longterm hemodialysis treatment] [article in German]. Schweiz Med Wochenschr. 1982;112:824-828. 2. Molzahn AE, Northcott HC, Dossetor JB. Quality of life of individuals with end stage renal disease: perceptions of patients, nurses, and physicians. ANNA J. 1997;24:325-333. 3. Holley JL, Nespor S, Rault R. A comparison of reported sleep disorders in patients on chronic hemodialysis and continuous peritoneal dialysis. Am J Kidney Dis. 1992;19:156-161. 4. Perl J, Unruh ML, Chan CT. Sleep disorders in end-stage renal disease: markers of inadequate dialysis? Kidney Int. 2006;70:1687-1693. 5. Merlino G, Gigli GL, Valente M. Sleep disturbances in dialysis patients. J Nephrol 2008; 21 Suppl 13:S66-S70. 6. Littner MR, Kushida C, Wise M, et al. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep. 2005;28:113-121. 7. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-545. 8. Meoli AL, Casey KR, Clark RW, et al. Hypopnea in sleepdisordered breathing in adults. Sleep. 2001;24:469-470. 9. Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis. 1995;26:751-756. 10. Hui DS, Wong TY, Ko FW, et al. Prevalence of sleep disturbances in chinese patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 2000;36:783-788. 11. Lui SL, Ng F, Lo WK. Factors associated with sleep disorders 12.

13. 14.

15.

16.

17.

in Chinese patients on continuous ambulatory peritoneal dialysis. Perit Dial Int. 2002;22:677-682. Yang JY, Huang JW, Peng YS, et al. Quality of sleep and psychosocial factors for patients undergoing peritoneal dialysis. Perit Dial Int. 2007;27:675-680. Zoccali C, Mallamaci F, Tripepi G. Sleep apnea in renal patients. J Am Soc Nephrol. 2001;12:2854-2859. Stepanski E, Faber M, Zorick F, Basner R, Roth T. Sleep disorders in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 1995;6:192-197. Kutner NG, Zhang R, Huang Y, Bliwise DL. Association of sleep difficulty with kidney disease quality of life cognitive function score reported by patients who recently started dialysis. Clin J Am Soc Nephrol. 2007;2:284-289. Wadhwa NK, Seliger M, Greenberg HE, Bergofsky E, Mendelson WB. Sleep related respiratory disorders in end-stage renal disease patients on peritoneal dialysis. Perit Dial Int. 1992;12:51-56. Rodriguez A, Stewart D, Hotchkiss M, Farrell P, Kliger A, Finkelstein F. Sleep apnea in CAPD. Adv Perit Dial. 1995;11:123-126. patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis. J Am Soc Nephrol.

18. Tang SC, Lam B, Ku PP, et al. Alleviation of sleep apnea in

2006;17:2607-2616. 19. Kumagai T, Ishibashi Y, Kawarazaki H, et al. Effects of nocturnal oxygen therapy on sleep apnea syndrome in peritoneal dialysis patients. Clin Nephrol. 2008;70:332-339. 20. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230-1235.

324

TANG.indd 324

22-06-2009 13:51:25

JNEPHROL 2009; 22: 318-325

21. Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344:102-107. 22. Chan CT, Hanly P, Gabor J, Picton P, Pierratos A, Floras JS. Impact of nocturnal hemodialysis on the variability of heart rate and duration of hypoxemia during sleep. Kidney Int. 2004;65:661-665. 23. Unruh ML, Sanders MH, Redline S, et al. Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol. 2006;17:3503-3509. 24. Auckley DH, Schmidt-Nowara W, Brown LK. Reversal of sleep apnea hypopnea syndrome in end-stage renal disease after kidney transplantation. Am J Kidney Dis. 1999;34:739-744. 25. Beecroft JM, Zaltzman J, Prasad R, Meliton G, Hanly PJ. Impact of kidney transplantation on sleep apnoea in patients with end-stage renal disease. Nephrol Dial Transplant. 2007;22:3028-3033. 26. Tang SC, Lam B, Lai AS, et al. Improvement in sleep apnea during nocturnal peritoneal dialysis is associated with reduced airway congestion and better uremic clearance. Clin J Am Soc Nephrol. 2009;4:410-418. 27. Chiu KL, Ryan CM, Shiota S, et al. Fluid shift by lower body positive pressure increases pharyngeal resistance in healthy subjects. Am J Respir Crit Care Med. 2006;174:1378-1383. 28. Welch KC, Foster GD, Ritter CT, et al. A novel volumetric magnetic resonance imaging paradigm to study upper airway anatomy. Sleep. 2002;25:532-542. 29. Stuck BA, Maurer JT. Airway evaluation in obstructive sleep

apnea. Sleep Med Rev. 2008;12:411-436. 30. Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane PA, Hanly PJ. Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea. Eur Respir J. 2007;30:965-971. 31. Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease. Nephrol Dial Transplant. 2008;23:673-679. 32. Kohnen R, Allen RP, Benes H, et al. Assessment of restless legs syndrome: methodological approaches for use in practice and clinical trials. Mov Disord. 2007; 22 (Suppl 18):S485-S494. 33. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C. Epidemiology of restless legs symptoms in adults. Arch Intern Med. 2000;160:2137-2141. 34. Unruh ML, Levey AS, DAmbrosio C, Fink NE, Powe NR, Meyer KB. Restless legs symptoms among incident dialysis patients: association with lower quality of life and shorter survival. Am J Kidney Dis. 2004;43:900-909. 35. Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 2000;54:1698-1700.
Received: February 24, 2009 Accepted: March 13, 2009

Societ Italiana di Nefrologia

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