Continuous ambulatory peritoneal dialysis (CAPD) is one of the principal methods of renal replacement therapy for patients with end-stage renal disease (ESRD). On account of its simple equipment, easy operation, clearance of middle molecular substances more effectively, better protection of residual renal function, and other features, this therapeutic method is accepted by more and more patients. In recent years, several studies have found that the incidence rate of sleep disorders in chronic peritoneal dialysis patients is 60%-80%.1–3 Since sleep disorders not only are associated with lower quality of life in patients, but also increase the incidence of cardiovascular events,1 sleep quality is considered as an independent factor of death in chronic peritoneal dialysis patients.2 A survey from the general population showed that sleep deprivation adversely affects cognitive function and biological pathways,4 while other studies concluded that sleep disorders can lead to many symptoms such as depression5 and RLS.6 However, limited data are available on related research of sleep disorders and their influence factors in this population. Therefore, we investigated the sleep situation and its related factors in peritoneal dialysis patients so as to provide a basis for clinical intervention for the treatment of mood/sleep disorders in ESRD patients on maintenance dialysis.
Forty-two patients from June 2013 to July 2013 were recruited in the Department of Blood Purification of Beijing Chao-Yang Hospital, Capital Medical University, China. The inclusion criteria of this study were age ≥18 years and CAPD with daily 6–8 L dialysis dose for more than 3 months. Patients were not included in the study if they had heart failure, a recent acute coronary event, cancer, autoimmune disease, and active infection.
The study was approved by the ethics committee of Beijing Chao-Yang Hospital, Capital Medical University, and written informed consent was obtained from each participant.
Assessment of sleep quality
The Pittsburgh Sleep Quality Index (PSQI) was applied to assess the patient's quality of sleep. PSQI is constituted by a 23-item self-rated questionnaire for the evaluation of sleep quality within the preceding month, which is divided into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of medication for sleep, and daytime dysfunction due to poor sleep. Each component score is calculated and coded from 0 to 3, where 0 indicates “no difficulty” and 3 “severe difficulty.” The global score ranges from 0 to 21, where scores of ≤5 indicate good sleep quality and scores of >5 indicate poor sleep quality.7
Assessment of depressive symptoms
The Hamilton Depression Rating Scale (HAMD) has since become the gold standard for measuring depressive symptom severity and change in randomized clinical trials, which can assess mood, insomnia, anhedonia, agitation, gastro-intestinal and other somatic symptoms, weight change, suicidal ideation, hypochondriasis, anosognosia, psychomotor, and cognitive retardation of patients. A global HAMD score ≥8 was considered as the presence of depression status in a patient.
Assessment of restless legs syndrome (RLS)
Restless legs syndrome (RLS) was diagnosed when patients meet the following four criteria developed by the International Restless Legs Syndrome Study Group: compelling urge to move the limbs, usually associated with paresthesias/dysesthesias; motor restlessness, as seen in activities such as floor pacing, tossing and turning in bed, and rubbing the legs; symptoms that worsen or are exclusively present at rest (i.e., lying, sitting), with variable and temporary relief on activity; and circadian variation of symptoms that are present in the evening and at night. The symptoms are often relieved after 5:00 am, but in more severe cases, they can be present throughout the day without circadian variation.8,9
Basic information collection
The age, gender, dialysis duration, serum creatinine, blood urea nitrogen (BUN), albumin (Alb), hemoglobin (Hb), hematocrit, calcium-phosphate product, intact parathyroid hormone (iPTH), and other biochemical parameters of ESRD patients were recorded. Besides, the occurrence of hypertension, diabetes, and pruritus of ESRD patients were also noted down.
Questionnaires were issued, explained, and recycled by a special messenger. Subjects completed the questionnaire in 10–15 minutes. The questionnaires were completed by the patients if they were educated. Otherwise, a registered nurse asked questions to gather information. Forty-two questionnaires were distributed and retrieved, with the response rate of 100%.
The SPSS version 13.0 statistics package (SPSS Inc., USA) was employed for the statistical analysis. Measurement data were presented as mean ± standard deviation (SD). Comparisons were performed using independent-samples t-test or χ2 test. In addition, bivariate correlation analysis and multiple regression analysis were performed. P value less than 0.05 was regarded as statistically significant.
Forty-two ESRD patients (23 females and 19 males) on CAPD for at least 3 months, with a mean age of (61.5±12.7) years (range 30–78 years) were recruited in this crosssectional study. Dialysis duration was (56.3±18.4) months (range 29–87 months), average residual renal function was (1.7±0.4) ml/min, and daily dialysis dose was 6–8 L. The etiology for ESRD was chronic glomerulonephritis (three cases), chronic interstitial nephritis (eight cases), hypertensive nephropathy (five cases), diabetic nephropathy (20 cases), and unidentified (six cases).
Prevalence of sleep disorders in peritoneal dialysis patients
According to the PSQI assessment, 20 peritoneal dialysis patients had poor quality sleep when compared to normal group (mean PSQI score 11.5±4.6 vs. 4.0±0.2), and the morbidity was 47.6%. In these 20 patients, nine cases suffered from more serious sleep disorders (PSQI >10), accounting for 21.4%. The PSQI scores of patients with or without sleep disorders are listed in Table 1.
Table 2 summarizes the clinical characteristics of the study cohort. Forty-two ESRD patients (23 females and 19 males) on CAPD for at least 3 months, with mean age of (61.5±12.7) years (range 30–78 years) and a mean dialysis duration of (56.3±18.4) months (range 29–87 months), were recruited. The etiology for ESRD was chronic glomerulonephritis (three cases), hypertensive nephropathy (five cases), diabetic nephropathy (20 cases), chronic interstitial nephritis (eight cases), and unidentified (six cases). Patients were grouped into the CAPD patients with sleep disorders (n=22) or CAPD patients without sleep disorders group (n=20) by PSQI assessment. There was no significant difference between the two groups in terms of age, sex ratio, dialysis duration, protopathy, serum creatinine, BUN, Hb, Alb, calcium (Ca), phosphorus (P), iPTH, and β2-microglobulin (β2-MG) (P >0.05). But the level of serum Alb in the CAPD patients with sleep disorders was significantly lower than that in CAPD patients without sleep disorders. And the prevalence of RLS and depression were significantly higher than those in CAPD patients without sleep disorders (P <0.05).
Influence of RLS, depression, and serum albumin levels on sleep disorders in CAPD patients
Among the 42 CAPD patients, 12 patients suffered from RLS and eight patients suffered from depression. In CAPD patients with RLS, the prevalence of sleep disorders was significantly higher than that in CAPD patients without RLS (11/22 vs. 11/30, χ2=10.395, P=0.001). And in CAPD patients with depression, the prevalence of sleep disorders was significantly higher than that in CAPD patients without depression (7/8 vs. 15/34, χ2=4.886, P=0.027). In CAPD patients, bivariate correlation analysis showed that sleep disorder was negatively correlated with serum Alb (r= -0.606, P=0.000) and positively correlated with RLS (r=0.497, P=0.001) and depression (r=0.341, P=0.029). On multiple regression analysis, RLS, depression, and low serum Alb were the independent risk factors of sleep disorders in CAPD patients after adjusting for age, gender, dialysis duration, and Hb (Table 3).
Although there have been improvements in ESRD treatment, patients have to face many significant problems with their quality of life. The presence of sleep disorders appears to be associated with decreased quality of life and higher mortality in patients on dialysis.10,11 Many studies reported that the prevalence of sleep disorders in adult dialysis patients was 50%-80%.12,13 Similarly, we also found that the prevalence of poor sleep quality in our patients was 47.6% by using the sleep measure (PSQI), and there were 21.4% cases suffering from more serious sleep disorders (PSQI >10) in this study. Sleep disorders appear to have negative impacts on the patient lives of dialysis, which can lead to daytime sleepiness, mood problems, impaired work performance, and increased accidents.14 More importantly, several studies have suggested that sleep disorders may increase the incidence and risk of hypertension, cardiovascular disease, and stroke.15–17 As we all know that further understanding the risk factors of sleep disorders helps to improve the intervention and therapy for these patients, it is very important to investigate the risk factors related to sleep disorders and improve the quality of sleep in ESRD patients.
Various types of sleep disorders are extremely common in dialysis patients. Frequent sleep disorders in patients on dialysis include sleep apnea syndrome, RLS, and periodic limb movement disorder. RLS is a sensory-motor neurological disorder characterized by an irresistible urge to move one's extremities. This unpleasant sensation becomes worse during inactivity and especially at night.18 RLS is one of the most unpleasant complaints in patients undergoing dialysis, with a reported range between 6% and 60%.19 Allen et al20 reported that RLS could induce sleep deprivation, which in turn evokes alterations in anabolic hormones secretion and circulation such as in growth hormone and insulin-like growth factor I, eventually affecting the patient's anabolism and muscle mass.21,22 Our previous study also found that the prevalence of RLS was 26.3% in hemodialysis patients, and the patients with RLS had varying degrees of sleep disorders.23 In this study, we further detected the relationship of RLS and sleep disorders in CAPD patients and found the morbidity of RLS was significantly higher in CAPD patients with sleep disorders than those without sleep disorders. Moreover, Logistic regression analysis showed that RLS was the independent risk factor of sleep disorders in CAPD patients. Therefore, we considered that RLS may be a potential risk factor to aggravate sleep disorders in CAPD patients and then ultimately decreased the patients’ quality of life and even increased their mortality through increasing cardiovascular burden.
Depression is highly prevalent in patients on dialysis, which consists of a constellation of symptoms including anhedonia, feelings of sadness, helplessness, hopelessness, and guilt. It is accompanied by changes in sleep, appetite, and libido24 and is associated with increased mortality and higher rate of suicides in these patients.25,26 Although some reports showed that 12%-26% of dialysis patients suffer from depression,5 few studies have evaluated the relationship between sleep disorders and depression in dialysis patients. Paparrigopoulos et al27 found that depression was an independent predictor associated with insomnia in ESRD patients as measured by the Hospital Anxiety and Depression Scale. Using the Epidemiological Studies of Depression (CESD) Scale, Rodriguez et al28 demonstrated that among maintenance hemodialysis patients, individuals with worse sleep have more symptoms of depression Consistent with these prior reports, we also observed a significant high prevalence of depression in CAPD patients with sleep disorders, and it was an independent risk factor of sleep disorders. However, the mechanism of depression related to sleep disorders is under investigation. A few studies proved that proinflammatory cytokines such as C-reactive protein29 and interleukin-630 may play an important role in the pathogenesis of depression, because they are all elevated in CAPD patients. Additionally, depression is associated with higher cardiovascular risk.31
Interestingly, we found the level of serum Alb in the CAPD patients with sleep disorders was significantly lower than that of the patients without sleep disorders, and the logistic regression analysis showed that serum Alb was an independent risk factor of sleep disorders in CAPD patients. Similar to our results, Li et al1 showed that patients with sleep disorders had lower serum Alb; and malnutrition and serum Alb were independent predictors of sleep disturbance in CAPD patients. But differing with our results, another study suggested that although serum Alb decreased in patients with sleep disorders, it was not the risk factor of poor sleep quality.32 These results indicate that poor sleepers had lower nutritional indices, and energy homeostasis disruption may adversely sleep abnormalities.
In conclusion, sleep disorders in CAPD patients are associated with higher illness intrusiveness which induced disruptions to lifestyles and activities. Our present findings indicated that RLS, depression, and low Alb are independent risk factors of sleep disorders in CAPD patients through the standard assessment, which can decrease the quality of life and increase morbidity and mortality risk in this population. Thus, we believe that our findings may provide a clinical thought for intervention for these risk factors and sleep disorders, and further improve psychological state and quality of life of CAPD patients.
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