Sleep disorders and illness intrusiveness in patients on chronic dialysis

Nephrol Dial Transplant (2004) 19: 1815–1822 DOI: 10.1093/ndt/gfh130

Original Article

Sleep disorders and illness intrusiveness in patients on chronic dialysis Istvan Mucsi1,2,3, Miklos Zs. Molnar MD1,4, Janos Rethelyi1, Eszter Vamos1, Gabor Csepanyi1, Gyorgyi Tompa5, Szabolcs Barotfi1,6, Adrienn Marton2 and Marta Novak1,7 1

Psychonephrology Study Group, Institute of Behavioral Sciences and 21st Department of Internal Medicine, Semmelweis University Budapest, 42nd Department of Internal Medicine, St Margaret Hospital, 5Nephrocentrum Foundation and 6 Quintiles Hungary Ltd, Budapest, Hungary, 3Department of Medicine, Faculty of Medicine and 7Sleep Research Laboratory, Department of Psychiatry, University Health Network, University of Toronto, Canada

Abstract Background. The prevalence of sleep problems (insomnia, restless legs syndrome, periodic limb movements in sleep and sleep apnoea) has been shown to be high in patients with end-stage renal disease (ESRD) and might contribute to impaired quality of life in this population. Methods. In a cross-sectional study using selfadministered questionnaires, we examined the prevalence of sleep disorders and assessed their effect on different aspects of health-related quality of life in a sample of Hungarian patients on maintenance dialysis. Results. Our data confirm that sleep problems are frequent in patients with ESRD; 65% of the patients reported symptoms of at least one specific sleep disorder; insomnia was the most common sleep complaint with 49%, the prevalence of sleep apnoea was 32% and the prevalence of restless legs syndrome was 15%. Co-morbidity, assessed by the End-Stage Renal Disease Severity Index, was shown to be an independent predictor of sleep disorders. Patients with sleep disorders reported higher illness intrusiveness and worse self-perceived health than those without sleep problems. The presence of sleep disorders was an independent predictor of illness intrusiveness, an important determinant of health-related quality of life. Conclusion. Sleep disorders are important determinants of illness intrusiveness and health-related quality of life in patients with ESRD. Sleep problems may be treated successfully; therefore, more attention should be paid to assessing these problems in this patient population.

Correspondence and offprint requests to: Dr Istvan Mucsi, 21 Mayfair Avenue, Apt. 414, Toronto, ON M5N 2N5 Canada. Email: [email protected]

Keywords: illness intrusiveness; insomnia; restless legs syndrome; self-perceived health; sleep apnoea; sleep disorders

Introduction Sleep complaints and their aetiology in patients with end-stage renal disease (ESRD) have received increasing attention over the last 10 years. Several studies have shown that disorders of sleep and wakefulness are prevalent in these patients. Earlier reports suggested that 30–80% of these patients complain of sleep-related problems, including insomnia, restless legs syndrome (RLS), periodic limb movements in sleep (PLMS) and sleep apnoea syndrome (SAS) [1]. Earlier studies reported large variations in the prevalence of the different sleep disorders. This could be attributed in part to the heterogeneity of the study populations and also to differences of the definitions and criteria of sleep disorders. Furthermore, validated instruments to detect specific sleep disorders were not used in most of the earlier surveys assessing sleep complaints in patients with ESRD. In those works, the presence or absence of sleep problems was determined by asking only a few questions about the key symptoms of sleep disorders. Insomnia and RLS can be diagnosed relatively easily from the history and hetero-anamnesis. However, validated sleep questionnaires may be helpful for the assessment of patients with sleep disorders. Recently, specific self-administered tools have been developed and validated to screen and/or diagnose SAS and RLS [2,3]. Recent evidence suggests a potential link between sleep deprivation, poor sleep quality and sleep disorders, and increased mortality. In renal patients, PLMS and RLS have been shown to be independent

Nephrol Dial Transplant Vol. 19 No. 7 ß ERA–EDTA 2004; all rights reserved

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predictors of mortality [4,5]. SAS might have a special significance since it may contribute to the increased cardiovascular morbidity and mortality of patients with ESRD. Sleep apnoea might also play a role in the development of specific symptoms (cognitive impairment and other neuropsychiatric problems, and fatigue) which previously were attributed to uraemia. Furthermore, nocturnal hypoxaemia recently has been shown to predict fatal and non-fatal cardiovascular events in chronic dialysis patients [6]. Symptoms and complications of the disease and also treatment factors have an important effect on quality of life (QoL) as perceived by the patients. QoL has been recognized as an independent and important predictor of patient morbidity and mortality. Certain sleep disorders cause excessive daytime sleepiness (EDS) that will have a negative impact on many aspects of everyday life. Furthermore, studies have suggested that sleep disorders may contribute to impaired QoL. Recently, this correlation has also been demonstrated in patients with ESRD [7,8]. The QoL of patients with ESRD is influenced by many clinical and psychosocial factors. Many of those important factors will modulate self-rated health (SRH), that reflects the subjective perception of overall health status determined in part by the ‘objective’ severity of the disease and also by the subjective characteristics of the patient. SRH has been shown consistently to predict survival in a variety of patient populations even after controlling for known prognostic factors. Furthermore, SRH corresponds significantly to objective indicators of health among ESRD patients [9]. Illness intrusiveness was introduced as a concept to represent illness-induced disruptions to lifestyles, activities and interests that compromise QoL [10]. Psychological and social factors act as moderator variables that influence the magnitude of illness intrusiveness occasioned by disease and treatment factors. The aim of our study was to determine the prevalence of specific sleep disorders in patients on maintenance dialysis. Furthermore, we wanted to analyse predictors of sleep disorders in this population. Finally, we studied the effect of sleep problems on important determinants of health-related QoL, such as SRH and illness intrusiveness. According to our hypothesis, sleep disorders would have a negative impact on important aspects of QoL in patients on maintenance dialysis. In our population, insomnia was the most common sleep problem and the prevalence of sleep disorders was similar to previously reported data. We showed that the severity of co-morbid conditions was an independent predictor of the presence of sleep disorders. Independent of other parameters, sleep disorders had a negative impact on illness intrusiveness.

Subjects and methods In two dialysis centres in Budapest, 78 out-patients on maintenance dialysis completed a self-administered

I. Mucsi et al.

questionnaire assessing the presence of sleep-related problems, self-perceived health and illness intrusiveness. The study population has been recruited from two dialysis units. All the patients dialysed for at least 3 months in a free-standing dialysis unit in Budapest (58 patients) were approached and asked to participate in the survey; 57 of them agreed to participate. In addition, 22 patients dialysed for at least 3 months at the FMC-SE Dialysis Centre at the 1st Department of Internal Medicine of the Semmelweis University Budapest were asked to participate; 21 of them agreed. This latter group were selected as their primary nephrologist was one of the authors (I.M.). No pre-defined selection criteria have been applied other than (i) willingness and ability to participate; and (ii) receiving chronic dialyisis for at least 3 months at the time of the study. Data describing the basic socio-demographic characteristics of the patients and the most important laboratory parameters were also tabulated. The study has been approved by the Ethics Committee of the Semmelweis University. Before enrolment, patients received detailed written and verbal information regarding the aims and protocol of the study. Patients completed the questionnaire during or before dialysis sessions. A trained research assistant provided help if necessary.

Assessment of sleep disorders To assess insomnia, we evaluated the presence and frequency of the most frequent symptoms (such as difficulty falling asleep or maintaining sleep, non-refreshing sleep, inadequate sleep duration). Patients were considered insomniacs if they reported at least one of the symptoms to be ‘frequent’. Symptoms of SAS were assessed using the Berlin Sleep Apnoea Questionnaire [2]. Based on the answers to the questionnaire, patients are categorized as high or low risk for SAS. RLS was diagnosed by using the RLS Diagnostic Scale [3]. PLMS, which often occurs together with RLS, has been assessed by the presence of two key symptoms, such as rapid, repeated leg kicks during sleep observed by the bed partner and awakenings during the night because of leg movements. Patients indicating both symptoms as ‘frequent’ were considered as having PLMS.

Assessment of daytime sleepiness Excessive sleepiness was assessed by the Epworth Sleepiness Scale (ESS) [11]. The scale aims to determine how much a person feels sleepy in every-day situations. Higher scores indicate more sleepiness, and scores above 8 indicate significant sleepiness.

Health-related quality of life Self-perceived health, an important aspect of health-related QoL, was measured using the visual analogue scale (VAS) of the EuroQOL scale [12]. This is a scale with 0–100 range where patients indicate their actual health status as they currently perceive it (100 corresponds to the best and 0 the worst possible health). Illness intrusiveness was assessed using the Illness Intrusiveness Ratings Scale (IIRS), which assesses the extent to which one’s ‘illness and/or its treatment interfere’

Sleep and illness intrusiveness in dialysis patients

with 13 life domains central to QoL. The scale has been used in different patient populations with various chronic conditions including renal patients, and it has been proven to have excellent psychometric properties [13]. Validation of the Hungarian version of the IIRS has been completed by our group recently (M. Novak et al., submitted).

1817 Table 1. Demographic and clinical characteristics of the patients and average scores of the scales employed Parameter

(Min–max)

Data on the weekly dialysis time, time since the start of dialysis, history of previous transplant, as well as sex, age, body weight and the frequency of hypnotic intake were tabulated. Serum albumin, haemoglobin, serum iron, type of renal disease and dialysis dose (Kt/V) were extracted from the patients’ charts.

Age (years; mean±SD) 59±14 Gender: male/female (%) 37/41 (47/53) Diabetes: yes/no (%) 21/57 (27/73) Time on dialysis (months; median) 30 ESRD-SI (co-morbidity) 16.3±11.5 Serum haemoglobin 107±13 Serum albumin 38.1±4.2 Kt/V 1.24±0.29 History of transplantation: yes/no (%) 5/72 (7/93) Self-perceived health 61±22 Epworth Sleepiness Scale (median) 5.5 Illness Intrusiveness Ratings Scale 40±16

Co-morbidity

Number and percentage of patients (%), and mean±SD are given, unless indicated otherwise.

Laboratory parameters and socio-demographic data

The severity of co-morbid conditions was assessed with the ‘End-Stage Renal Disease Severity Index’ (ESRD-SI) [14]. The ESRD-SI is completed by the patients’ primary nephrologist. The nephrologist is asked to rate the severity of 12 common co-morbid conditions on scales ranging from 0 to 10. The conditions evaluated in the scale are: cardiac disease, cerebrovascular disease, peripheral vascular disease, peripheral neuropathy, bone disease, respiratory disorders, impaired vision, autonomic neuropathy and gastrointestinal symptoms, dialysis-related events, diabetes and other undefined conditions. This instrument has been shown to be a reliable indicator of co-morbidity in ESRD [15].

Statistics Statistical analysis was carried out using the SPSS software. Results are shown as mean±SD or median (min–max) if the distribution of data deviated from normal. Groups with and without sleep disorders were compared with Student’s t-test, analysis of variance (ANOVA) or the Mann–Whitney U-test, as appropriate. The 2 square test was used to analyse categorical variables. Predictors of sleep disorders and survival were assessed using logistic regression analysis. Predictors of daytime sleepiness, SRH and IIRS were determined using linear regression analysis with stepwise inclusion of variables.

Results The main characteristics of the patients enrolled in the study are shown in Table 1. Although the sample is small and has not been selected randomly, the main socio-demographic characteristics are similar overall to the characteristics of the Hungarian dialysis population. In a recently completed study, we obtained data on 630 patients dialysed in 10 dialysis units in Budapest. The basic characteristics of our sample presented herein are very similar to the characteristics of the larger cohort (data not shown). Of the 80 patients approached, 78 (97.5%) agreed to participate in the study. Information on the underlying renal disease leading to ESRD was extracted from the

24–84 3–213 0–48 73–151 17–49 0.48–1.92 3–100 0–18 13–85

charts: 6% of the patients had chronic glomerulonephritis, 15% chronic pyelonephritis, 12% polycystic kidney disease, 27% diabetic nephropathy, 6% ischaemic nephropathy, 13% hypertensive nephropathy and 11% other diseases. In 10% of the patients, we could not identify the underlying renal disease. Prevalence and predictors of sleep disorders We found a high prevalence of sleep disorders in our sample: similarly to previous reports, insomnia was the most common sleep disorder, with 49% of the patients reporting symptoms of this condition. Based on the Berlin Questionnaire, 32% of the patients were classified as high risk for sleep apnoea, whereas RLS was diagnosed in 15% of the participants. The prevalence of sleep-related movement disorders (RLS and PLMS together) was 30% and in further analysis this group was considered instead of the RLS group. Overall, 65% of the patients showed symptoms of at least one sleep problem and 21% of them reported more than one. Demographic and laboratory data of patients with and without sleep disorders (insomnia, risk for sleep apnoea and RLS/PLMS) are shown in Table 2. Demographic parameters and laboratory data did not differ between the groups with or without sleep disorders. The distribution of men and women did not differ in patients with or without insomnia, patients with high vs low risk for sleep apnoea and patients with movement disorders vs no movement disorders. We also found no differences in the prevalence of sleep disorders amongst patients with or without diabetes. Co-morbidity in the sample, as assessed with the ESRD-SI, showed a negative correlation with serum albumin (r ¼
0.259, P