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| ORIGINAL ARTICLE |
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| Year : 2016 | Volume
: 53
| Issue : 1 | Page : 48-53 |
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Sleep disorders in chronic kidney disease patients
Mohamed Eltawdy1, Amany Rabah1, Mona Nada2, Rasha Refaat1, Lamia Afifi2
1 Department of Neurology, Cairo University, Cairo, Egypt
2 Clinical Neurophysiology Unit, Cairo University, Cairo, Egypt
| Date of Submission | 07-Apr-2015 |
| Date of Acceptance | 03-Aug-2015 |
| Date of Web Publication | 15-Feb-2016 |
Correspondence Address:
Lamia Afifi
MD, 7 Dr. Shaheen St, Al Agooza, Cairo 12311
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1110-1083.176372
Background
Sleep complaints are frequent among chronic kidney disease (CKD) patients.
Objective
We aimed to subjectively and objectively assess sleep disturbances in CKD patients and compare them between those who undergo hemodialysis (HD) and those who do not.
Patients and methods
The study was conducted on 40 CKD patients who were subdivided into two groups; group I included patients not undergoing HD (n = 20), and group II included patients on regular HD (n = 20). A total of 20 matched healthy volunteers participated as controls. Patients completed Epworth Sleepiness Scale, a sleep questionnaire, and underwent an attended polysomnography.
Results
All patients had sleep complaints in the form of excessive daytime sleepiness, difficulty falling asleep, early morning awakening, jerking leg movements, and fragmented sleep. CKD patients had lower total sleep time, sleep efficiency, slow wave sleep (SWS) percentage, oxygen desaturation, and higher respiratory distress and periodic limb movement (PLM) indices compared with controls. Group II patients showed a higher Epworth Sleepiness Scale and more frequent complaints of leg jerks. Furthermore, group II patients showed higher sleep efficiency and PLM compared with group I. Patients' age positively correlated with respiratory distress index and negatively correlated with total sleep time and oxygen saturation. The duration of illness and duration of dialysis positively correlated with the number of awakenings.
Conclusion
There is a high prevalence of sleep disorders in CKD patients whether they were on regular PLMs. Achieving a more complete understanding of sleep problems experienced by these patients can improve quality of life and patient survival. Keywords: Chronic kidney disease, hemodialysis, polysomnography, sleep disorders
How to cite this article:
Eltawdy M, Rabah A, Nada M, Refaat R, Afifi L. Sleep disorders in chronic kidney disease patients. Egypt J Neurol Psychiatry Neurosurg 2016;53:48-53 |
How to cite this URL:
Eltawdy M, Rabah A, Nada M, Refaat R, Afifi L. Sleep disorders in chronic kidney disease patients. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2023 Dec 7];53:48-53. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/1/48/176372 |
| Introduction | |  |
Chronic kidney disease (CKD) patients were reported to have frequent sleep complaints. Prevalence of sleep complaints in CKD patients have ranged from 55 to 80% [1],[2]. These sleep complaints include insomnia, restless legs, snoring, excessive daytime sleepiness (EDS), and nightmares. Some data show that sleep complaints are present even at early stages of the disease and may affect more than 80% of the early CKD patients without any relationship to comorbidities [3]. This increased prevalence of sleep complaints was also found in patients with end-stage renal disease who underwent hemodialysis (HD) as poor sleep quality was reported in more than 85% of dialysis patients, including both peritoneal dialysis and HD patients [4],[5].
Sleep disturbances in CKD patients have negative effects on quality of life, functional health, morbidity, and mortality [6]. Specific therapeutic regimen of sleep disorders could improve the quality of life in these patients. However, accurate diagnosis, including polysomnography (PSG) recordings, is essential to plan a regimen. Several studies have assessed either subjective or, less commonly, objective sleep disturbances in CKD or HD patients separately, but data are deficient in comprehensive studies evaluating both subjective sleep complaints and polysomnographic measures in CKD and HD patients with direct comparison between both groups. Therefore, the aim of this work was to assess, both subjectively and objectively, the prevalence and types of sleep disorders in CKD patients and whether HD has any effect on these sleep disorders.
| Patients and methods | | |
Patients
A total of 40 patients with CKD and 20 healthy controls participated in the study. We included CKD patients who had been diagnosed with stage IV-V CKD. The stage of CKD was determined using the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation [7]. The CKD patients were divided into two groups; group I included 20 CKD patients who were not undergoing HD [16 men and four women, aged 20-56 years (37.40 ± 13.08 years)] and group II included 20 CKD patients who were on regular daytime HD [18 men and two women, aged 21-62 years (43.40 ± 14.32 years)]. CKD patients were excluded from the study if they suffered from depression, manifestations of the central nervous system affection, hepatic impairment, had BMI greater than 23, or were on psychoactive medications or hypnotics. The control group comprised 20 healthy volunteers [15 men and five women, aged 20-70 years (40.3 + 17.26 years)]. The experimental procedures used were approved by the local institutional ethics committee. Written informed consent were obtained from all participants.
Methods
Questionnaires
All patients underwent thorough history-taking examination and completed the Epworth Sleepiness Scale (ESS), a questionnaire designed to evaluate a patient's level of subjective sleepiness by assessing the chance of dozing off in real-life situations [8]. The score range on the ESS is from 0 to 24: the higher the score the greater the level of subjective sleepiness. A score greater than 10 is often used to identify individuals with significant EDS. Internal consistency reliability, test-retest reliability, and validity of the ESS have been reported [9]. The participants also completed a sleep questionnaire that included questions about difficulty in falling asleep, fragmented sleep, early morning awakening, excess daytime sleepiness, respiratory complaints, and abnormal behavior during sleep [10].
Polysomnography
All participants underwent one night of laboratory-based PSG. PSG was carried out using Shwarzer Epos 32 GmpH Amplifier (Medical Diagnostic Equipment, Shwarzer, Germany) and Somnologica software (Broomfield, CO, USA). The following electrophysiological data were recorded: electroencephalography (C3/A2, C4/A1, O2/C3, and O1/C4), left and right electrooculography, mentalis and tibial electromyography, ECG, respiratory airflow measured by airflow cannula and thermistor, respiratory effort measured by chest and abdominal belts, finger pulse-oximetry, snoring neck microphone, and body position sensors. A physician experienced in sleep disorders scored the PSG was scored manually according to the American Academy of Sleep Medicine guidelines [11]. This physician was blinded to the participants being scored. Sleep measures obtained for each participant included total sleep time (TST), percentage of different sleep stages, sleep onset latency, number of awakenings, sleep efficiency (SE), respiratory disturbance index (RDI), oxygen saturation, and periodic limb movement index (PLMI).
Statistical analysis
All tests were carried out using SPSS (version 20 for Windows; SPSS Inc., Chicago, Illinois, USA). Descriptive statistics were used for parametric data and for categorical data. Two-tailed Student's t-tests were used for all parametric data when comparing between two groups. Correlations were assessed using the Pearson correlation coefficient. Results were presented as mean values ± SDs. A value of P less than 0.05 was used to define statistical significance.
| Results | | |
Demographic and clinical results
There were no significant differences between group I, group II, and the control group as regards age or sex distribution. The duration of illness was significantly longer in group II than in group I (8.93 ± 0.38 vs. 3.09 ± 2.56 years, P < 0.01). The duration of dialysis treatment among patients of group II ranged from 18 months to 9 years, with a mean of 4.75 ± 2.80 years.
Results of sleep scales
Epworth Sleepiness Scale
The ESS score was greater than 10 in 14 out of 40 CKD patients, which denoted the presence of EDS in nearly a third of CKD patients (35%). The ESS score was significantly higher in group II than in group I (9.90 ± 4.04 vs. 6.50 ± 2.59, P = 0.04).
Sleep complaints
We found that all CKD patients, whether in group I or II, complained of sleep disturbances. The prevalence of different sleep complaints was similar in both groups except for jerking leg movements, which was significantly higher in group II compared with group I [Table 1].
Results of polysomnography
Chronic kidney disease patients versus controls
The patient groups showed significantly less TST, SE, stage N3 percentage, and a higher number of awakenings and PLMI than did the control group. The patient groups also showed a higher RDI and a lower lowest oxygen concentration than did the control group [Table 2]. | Table 2: Sleep parameters in chronic kidney disease patients group and control group
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Comparison between group I and group II
Regarding sleep architecture, only SE was significantly lower in group I than in group II. There was no difference in the respiratory parameters between both groups. However, group II patients showed a significantly higher PLMI than did the group I patients [Table 3].
Clinical correlations
There was a significant negative correlation between age and TST, lowest O 2 , average O 2 in rapid eye movement (REM), and non-REM, and a significant positive correlation between age and N1 percentage, and RDI. There was a significant positive correlation between duration of illness and the number of awakening and PLMI only.
Regarding the duration of dialysis, there was a significant negative correlation between the duration of dialysis and the number of awakenings. There was no significant correlation between the duration of dialysis and other parameters of sleep [Table 4]. | Table 4: Correlation between age, duration of illness and duration of dialysis with sleep parameters
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| Discussion | | |
Sleep disturbances are common in CKD patients, including those on regular HD. Sleep complaints were reported by all the CKD patients included in this study. Prevalence of difficulty falling asleep, fragmented sleep, early morning awakening, excess daytime sleepiness, and leg jerking was higher in our patients than the figures cited for the general population [12]. This high prevalence of sleep complaints was similarly found during previous studies that reported up to 88% of CKD patients having sleep complaints, including symptoms suggestive of obstructive sleep apnea (OSA), restless leg syndrome , and REM behavior disorder [2-4]. It is imperative to diligently inquire about sleep disturbances in CKD as poor sleep quality was shown to be associated with significantly lower mental and physical health. It was even reported that the relative risk of mortality was 16% higher for HD patients with poor SQ [13].
The ESS showed that 35% of the CKD patients suffered from EDS. EDS in CKD has been commonly reported by previous studies with multiple hypotheses proposed to account for EDS, including subclinical uremic encephalopathy, change in body temperature rhythm resulting in a disturbance of the sleep-wakefulness cycle, tyrosine deficiency leading to decreased neurotransmitters associated with arousal, or coexistent primary sleep disorders as OSA or periodic limb movement disorder (PLMD) [14],[15],[16],[17].
When we compared the polysomnographic findings of all the CKD patients with the control group, we found a significant reduction in TST, SE, SWS, and a higher number of awakenings in the CKD group. Our findings are in agreement with those of the previous studies that reported decreased SWS , TST, and SE in CKD patients [18,19]. These findings add subjective evidence to the objective complaints of poor sleep quality reported by CKD patients.
The CKD patients showed significantly higher total RDI, and significantly lower lowest O 2 saturation in comparison with the controls. The association between CKD and sleep apnea (SA) has been well described. The prevalence of SA is almost 10 times greater in patients with CKD than in the general population, with data reporting a prevalence of almost 50% [19],[20],[21]. Patients with advanced CKD are predisposed to more severe RDI compared with patients with less advanced CKD [21]. SA is caused by both upper airway occlusion during sleep, causing obstructive apneas, or impaired central ventilatory control, causing central apneas. Upper airway occlusion in CKD can be caused by fluid overload and interstitial edema in the upper airway, which subsequently increases neck circumference and reduces upper airway cross-sectional area, contributing to the pathogenesis of OSA [22]. In contrast, the increased prevalence of central apnea in dialysis patients may be due to hypocapnia from metabolic acidosis and acidemia changing the apnea-PCO 2 threshold, thus predisposing the patients to an unstable breathing pattern [23]. An inverse relationship could also be true. A 30% prevalence of CKD was reported among patients with sleep-related breathing disorder [24]. Vascular endothelial growth factor and oxidative stress indicators have been demonstrated to be increased in SA patients and both potentially have a pathogenic role within the kidney [25],[26].
PLMI was significantly higher in the CKD patients than in the control group, which is in accordance with previous studies reporting a 30% prevalence of PLMD in CKD patients [19],[21]. Increased PLMD in CKD may be due to anemia secondary to decreased production of endogenous erythropoietin, iron and vitamin deficiencies, peripheral neuropathy, or alterations of dopamine and opioid synthesis metabolism [22]. The dopamine deficiency theory is supported by the low plasma levels of tyrosine, the amino acid precursor of dopamine, in patients with uremia [15].
The second focus of our study was the effect of HD on sleep in CKD patients. By comparing the subjective complaints between group I patients and group II patients we found that group II patients were more sleepy and complained more often of leg jerking than were the group I patients. The high EDS in the HD group is in agreement with a previous study conducted on 46 HD patients, which found that 30.4% of the patients had scores greater than or equal to 11 in the ESS, suggesting that clinically significant sleepiness was a problem for many of HD patients [27]. In addition to the factors theorized to cause EDS in CKD, HD adds more possible causes including the release of sleep-inducing inflammatory cytokines during dialysis and the effects of dialysate temperature on sleep [16]. Furthermore, the frequent napping during HD may alter the sleep-wake cycle in patients on regular HD and worsen night-time sleep. Indeed, it was found that up to 88% of the HD patients complain from poor sleep quality [4],[5].
The TST and percentage of different stages of sleep were similar between both groups. However, we found that group II patients had a higher SE than did group I patients. This difference in SE contradicts two previous studies that found that CKD patients had higher SE and lower arousal index compared with HD patients [18],[28]. A possible explanation for this difference in SE is that HD corrects neurotransmitter and electrolyte serum levels, which may improve consolidation of sleep.
PLMI was higher in group II compared with the group I. In addition to the factors causing PLMD in CKD, anemia secondary blood loss during HD is an additional risk factors for PLMD [29]. Peripheral neuropathy may be another factor causing increased PLMD in our HD group since group II patients had a longer duration of illness than did group I patients, and thus were more likely to have developed neuropathy with the longer duration of disease. RDI was similar between the two groups, indicating that HD does not modify the breathing pattern during sleep.
The age of our patients negatively correlated with TST, lowest O 2 , average O 2 in REM, and non-REM, and positively correlated with S1 percentage and RDI. Changes in sleep patterns, mainly decreased TST, and less SWS may be a normal part of aging, but many other factors common in older people contribute to sleep problems, including the frequent morbidity and medication use. In addition, the incidence of SA and PLMD is known to increase with age [30]. The effect of age was also reported in CKD as previous studies showed that poor sleep quality, assessed by sleep questionnaires, correlated with age [2],[4]. Our study showed that the duration of CKD illness positively correlated with number of awakenings and PMLI. To our knowledge, we are the first to correlate the duration of illness with sleep disturbances. This positive correlation between duration of illness and number of awakenings support the causal relationship between CKD and sleep disturbances. The duration of dialysis negatively correlated with the number of awakenings. In addition, there are no previous data on correlation between duration of dialysis and sleep disorders. It is possible that the longer patients undergo HD, the better they adjust their sleep-wake schedule to accommodate the treatment sessions without compromising nocturnal sleep.
In summary, our study was a comprehensive study assessing sleep complaints and PSG in CKD patients and correlating them to clinical variables. In addition, we compared those undergoing HD with those who were not. The results showed a very high incidence of sleep complaints in CKD patients. PSG confirmed the presence of sleep disorders in these patients including SA and PLMD. The HD patients differed from CKD in having a higher EDS and PLMD. Sleep complaints of patients with CKD and those receiving daytime HD require specific interventions and management. Further studies including a larger sample of patients are required for better understanding the risk factors associated with sleep disturbances and thus possible treatments in these patients. Clinicians face a considerable challenge in this regard, especially when managing CKD patients' complex clinical presentation and treatment needs.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Cohen SD, Patel SS, Khetpal P, Peterson RA, Kimmel PL. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease. Clin J Am Soc Nephrol 2007; 2 :919-925.  |
| 2. | Merlino G, Piani A, Dolso P, et al. Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant 2006; 21 :184-190. |
| 3. | De Santo RM, Bartiromo M, Cesare MC, Di Iorio BR. Sleeping disorders in early chronic kidney disease. Semin Nephrol 2006; 26 :64-67. |
| 4. | Eryavuz N, Yuksel S, Acarturk G, et al. Comparison of sleep quality between hemodialysis and peritoneal dialysis patients. Int Urol Nephrol 2008; 40 :785-791. |
| 5. | Masoumi M, Naini AE, Aghaghazvini R, Amra B, Gholamrezaei A. Sleep quality in patients on maintenance hemodialysis and peritoneal dialysis. Int J Prev Med 2013; 4 :165-172. |
| 6. | Parker KP. Sleep disturbances in dialysis patients. Sleep Med 2003; 7 :131-143. |
| 7. | National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39 :S1-266. [ PUBMED] |
| 8. | Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991; 14 :540-545. |
| 9. | Johns MW Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992; 15 :376-381. |
| 10. | Parkes JD. Daytime sleepiness. BMJ 1993; 306 :772-775. |
| 11. | American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Westchester: American Academy of Sleep Medicine; 2007. |
| 12. | Ohayon M. Epidemiology of sleep disorders in the general population. In: Guilleminault C, editor. Clinical neurophysiology of sleep disorders. Amsterdam: Elsevier; 2005. 139-154. |
| 13. | Elder SJ, Pisoni RL, Akizawa T, et al. Sleep quality predicts quality of life and mortality risk in haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2008; 23 :998-1004. |
| 14. | Hughes JR, Roxe DM, Greco F, et al. Electrophysiological studies on uremic patients - comparison of peritoneal dialysis and hemodialysis. Clin Electroencephalogr 1980; 11 :73-82. [ PUBMED] |
| 15. | Furst P. Amino acid metabolism in uremia. J Am Coll Nutr 1989; 8 :310-323. |
| 16. | Parker K, Bliwise D, Rye D. Hemodialysis disrupts basic sleep regulation: hypothesis building. Nursing Research 2000; 49 :327-332. |
| 17. | 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. |
| 18. | Parker KP, Bliwise DL, Bailey JL, Rye DB. Polysomnographic measures of nocturnal sleep in patients on chronic, intermittent daytime haemodialysisvs those with chronic kidney disease. Nephrol Dial Transplant 2005; 20 :1422-1428. |
| 19. | Jurado Gámez B, Martín-Malo A, Fernández Marín MC, et al. Sleep disorders in patients on a kidney transplant waiting list. Arch Bronconeumol 2008; 44 :371-375. |
| 20. | Hanly P. Sleep apnea and daytime sleepiness in end-stage renal disease. Semin Dial 2004; 17 :109-114. |
| 21. | Markou N, Kanakaki M, Myrianthefs P, et al. Sleep-disordered breathing in nondialyzed patients with chronic renal failure. Lung 2006; 184 :43-49. |
| 22. | Benz R, Pressman M, Masood I. Sleep disorders associated with chronic kidney disease. In: Göõz M, editor. Chronic kidney disease [ISBN: 978-953-51-0171-0] . Rijeka, Croatia: InTech; 2012. p. 385-400. Available at: http://www.intechopen.com/books/chronic-kidney-disease/sleep-disorders-associated-with-chronic-kidney-disease |
| 23. | Mendelson WB, Wadhwa NK, Greenberg HE, Gujavarty K, Bergofsky E. Effects of hemodialysis on sleep apnea syndrome in end-stage renal disease. Clin Nephrol 1990; 33 :247-251. |
| 24. | Iseki K, Tohyama K, Matsumoto T, Nakamura H. High prevalence of chronic kidney disease among patients with sleep related breathing disorder (SRBD). Hypertens Res 2008; 31 :249-255. |
| 25. | Schulz R, Hummel C, Heinemann S, Seeger W, Grimminger F. Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med 2002; 165 :67-70. |
| 26. | Yamauchi M, Nakano H, Maekawa J, et al. Oxidative stress in obstructive sleep apnea. Chest 2005; 127 :1674-1679. |
| 27. | Parker KP, Bliwise DL, Bailey JL, Rye DB. Daytime sleepiness in stable hemodialysis patients. Am J Kidney Dis 2003; 41 :394-402. |
| 28. | Roumelioti ME, Buysse DJ, Sanders MH, Strollo P, Newman AB, Unruh ML. Sleep-disordered breathing and excessive daytime sleepiness in chronic kidney disease and hemodialysis. Clin J Am Soc Nephrol 2011; 6 :986-994. |
| 29. | Rocco MV, Blumenkrantz MJ. Nutrition. In: Daudridas JT, Blake PG, Ing TS, editors. Handbook of dialysis. Philadelphia: Lippincott Williams & Wilkins; 2001. 420-445. |
| 30. | Edwards BA, O′Driscoll DM, Ali A, Jordan AS, Trinder J, Malhotra A. Aging and sleep: physiology and pathophysiology. Semin Respir Crit Care Med 2010; 3 :618-633. |
[Table 1], [Table 2], [Table 3], [Table 4]
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