Sleep-related breathing disorders impair quality of life in haemodialysis recipients

Bernd M. Sanner1,, Martin Tepel1, Martina Esser1, Joerg Klewer1, Beate Hoehmann-Riese1, Walter Zidek1 and Bernhard Hellmich2

1 Department of Medicine I, Marienhospital Herne, Ruhr University Bochum and 2 Department of Medicine, Ruhr University Bochum, Universitaetsklinik Bergmannsheil, Germany



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. It is well known that the quality of life of haemodialysis recipients is often severely compromised. So far, the influence of sleep-related breathing disorders on the quality of life of patients receiving maintenance dialysis has not been evaluated.

Methods. Quality of life as assessed by the Medical Outcomes Study Short Form-36 (SF-36) and the Nottingham Health Profile Part 1 (NHP1) was determined in 33 patients (20 males, 13 females; median age 66 years (95% CI 22–82)) with end-stage renal disease treated with haemodialysis. Additionally, polygraphy with a validated eight-channel ambulatory recording unit was performed.

Results. Twenty-one patients (63.6%) had a clinically significant sleep-related breathing disorder with a median apnoea/hypopnoea index of 13.3 (6.3–78.1)/h and a median oxygen saturation during sleep of 92.5 (88–97)%. In three out of eight subjective measures of the SF-36 (vitality, social functioning and mental health) and in one out of six subjective measures of the NHP1 (emotional reactions), patients without sleep-related breathing disorders had a higher quality of life than patients with this disorder (P<0.05 each). Furthermore, the severity of the sleep-related breathing disorder as indicated by the apnoea/hypopnoea index significantly correlated with the following quality of life measures: physical functioning, social functioning, role limitation due to physical and emotional problems, general health and vitality (SF-36), and also with pain, sleep, social isolation and emotional reactions (NHP1) (P<0.05 each).

Conclusions. We conclude that sleep-related breathing disorders independently influence the quality of life of patients receiving maintenance dialysis.

Keywords: dialysis; quality of life; sleep



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
In patients with end-stage renal disease, initiation of long-term dialysis treatment increases survival [1], but quality of life remains impaired compared with successful renal allotransplantation [2]. Therefore, researchers and clinicians generally agree that quality of life, its determinants and treatment options that may preserve subjective well-being merit continued investigation [2].

Patients with end-stage renal disease have a high incidence of sleep disorders, especially of periodic limb movements in sleep and sleep-related breathing disorders [3,4]. It is known that patients with sleep-related breathing disorders are prone to an increased cardiovascular morbidity and mortality [5]. Up to 70% of patients with end-stage renal disease have pathologic breathing patterns during the night [6]. So far, the influence of sleep-related breathing disorders on the quality of life in patients receiving maintenance dialysis has not been evaluated.

We therefore determined the quality of life using two quality of life measures in consecutive haemodialysis recipients and analysed the impact of sleep-disordered breathing. Since different quality of life scales measure different aspects of health decrement, and since it is not clear which of the standard measures is most suited to measuring the quality of life in patients with end-stage renal disease, we were interested in seeing how two different scales perform in this situation.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Patients
Men and women were eligible for the study if they were at least 18 years of age, had end-stage renal disease, and had been receiving maintenance haemodialysis treatment for at least 3 months. Criteria for exclusion were uncontrolled hypertension, malfunction of the vascular access (haemodialysis blood flow <300 ml/min, high return venous pressure and/or recirculation >15%), stroke, seizures, symptomatic ischaemic heart disease or congestive heart failure, the presence of severe associated disease, anaemia unrelated to chronic renal failure, use of sedatives and muscle relaxants, or refusal to participate in the study.

Evaluation of health-related quality of life
Two well established questionnaires were used to evaluate health-related quality of life: the Nottingham Health Profile Part 1 (NHP1) and the Medical Outcomes Study Short Form-36 (SF-36). Physicians instructed patients how to fill out the forms, and all patients completed them at home on a non-dialysis day.

The Nottingham Health Profile Part 1
The Nottingham Health Profile measures patients’ perception of their own health in terms of quality of life [7]. The Nottingham Health Profile has been widely used, and a number of different national versions have been produced. The questions were translated into and validated in German [8]. Part 1 measures the subjective health status by asking for responses (‘yes’ or ‘no') to a test of 38 simple statements relating to six dimensions of social functioning: emotional reactions, energy, pain, physical mobility, sleep and social isolation. All statements are related to limitations of activity or aspects of distress. The answers are weighted with specific values, which enable a score from 0 to 100 for each dimension. A high score indicates a high degree of limitation. The scores are usually presented as a profile and not added to an overall score.

SF-36 health survey questionnaire
SF-36 is a 36-item questionnaire that measures physical functioning, mental health, energy and vitality, pain, and general perception of health [9,10]. For each variable, scores are coded, summed, and transformed onto a scale from 0 (worst possible health) to 100 (best possible health). Two summary scores are calculated: physical (physical component summary) and emotional well-being (mental component summary). These summary scores replicate the results from the original eight variables of the SF-36. The SF-36 questionnaire has been used to measure decreased quality of life in several disorders, including end-stage renal failure and dialysis treatment [11].

Sleep study
All patients underwent overnight polygraphy on a dialysis day. Sleep-related breathing disorders were established by a 1-night sleep study with a validated eight-channel ambulatory recording unit (POLY-MESAM unit; MAP, Martinsried, Germany) [12]. The sleep study consisted of continuous polygraphic recording from a three-way thermistor that measured nasal/oral airflow, and from non-invasive leads measuring abdominal and chest-wall movements, oxygen saturation, heart rate, tracheal sounds (microphone), body position and limb movements (surface electrodes positioned over the M. tibialis anterior).

According to the commonly used clinical criteria [13], a breathing event was defined as abnormal if either a complete cessation of airflow lasting >=10 s took place (apnoea) or if a reduction in respiratory airflow of >=50% of the airflow lasting >10 s associated with a desaturation of >3% could be discerned (hypopnoea). Obstructive apnoea was defined as absence of airflow in the presence of paradoxical chest-wall motion. The average number of episodes of apnoea and hypopnoea per hour (apnoea/hypopnoea index) was calculated, and the mean and minimum oxygen saturations during the night were determined. Sleep-related breathing disorder was diagnosed when the apnoea/hypopnoea index was >=5/h. Sleep-related periodic EMG leg activity was scored according to standard criteria [14]. The average number of periodic limb movements per hour (periodic limb movement index) was calculated.

The study protocol was approved by the local ethics committee. All patients gave their informed consent before entry into the study.

Statistical analyses
Results are presented as medians (95% confidence interval). All P values reported are two-tailed. Statistical analyses were performed with the computer software SPSS for Windows (SPSS, Chicago, IL, USA). Intergroup differences were analysed for significance with the Mann–Whitney U-test with Bonferroni's correction for multiple comparisons.

The relationships between quality of life measures and parameters indicative of the severity of sleep-related breathing disorders were explored first by bivariate regression analysis (Spearman rank correlation coefficients). To determine the independent association of quality of life measures with the severity of sleep-related breathing disorders in the presence of other factors affecting quality of life, stepwise linear regression analysis was performed in a second step. The multivariate statistical model was built in steps and was designed to select only factors that correlated with the quality of life measures at a level of significance of <=0.05 for the final multiple regression model.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Thirty-three consecutive patients (20 males, 13 females) out of 78 patients with end-stage renal disease receiving maintenance dialysis were included in the study. As confirmed by clinical examination, patients were in a stable condition of health. No patient had significant pain, elevated temperature or other acute conditions. There were no shift workers in our population. The median age of patients was 66 years (range 22–82). Table 1Go shows the characteristics of the patients included in the study. All patients studied received haemodialysis treatment with a total of between 11.25 and 15 h of dialysis per week, equally divided into three sessions.


View this table:
[in this window]
[in a new window]
 
Table 1.  Patient characteristics of the 33 patients included in the study

 
Aetiology of renal failure among the patients studied was as follows: glomerulonephritis, 11 patients (33.3%); chronic pyelonephritis, seven (21.2%); diabetic nephropathy, six (18.2%); polycystic disease, three (9.1%); and other, including systemic lupus erythematosus, toxic nephropathy and obstructive nephropathy, six (18.2%).

Twenty-eight of the patients (84.8%) had systemic hypertension, 14 patients (42.4%) had coronary artery disease and 10 patients (30.3%) had diabetes mellitus. All hypertensive patients were treated with antihypertensive agents (19 with angiotensin-converting enzyme inhibitors, 18 with beta-blocking agents, 10 with calcium channel blockers, five with angiotensin receptor antagonists), 14 patients were treated with a diuretic agent, five with a nitrate, six with insulin, and 28 with recombinant human erythropoietin.

Sleep study
Twenty-one of the 33 patients (63.6%) had an apnoea/hypopnoea index of >=5/h. In this subgroup, the median apnoea/hypopnoea index was 13.3/h (range 6.3–78.1), the median oxygen saturation during the night was 92.5% (range 88–97), the minimum oxygen saturation during the night was 80% (range 63–93), and the time during the night with an oxygen saturation <90% was 8% (range 1–41). Twenty-two of the 33 patients (66.7%) had a periodic limb movement index of >=5/h. In this subgroup, the median periodic limb movement index was 38.2/h (range 7–156).

Patients with and without a sleep-related breathing disorder did not differ with respect to age, body mass index, months on dialysis, laboratory values (haemoglobin, creatinine, urea nitrogen), Kt/V, smoking habits, use of alcohol, associated diseases (especially hypertension, coronary artery disease and diabetes mellitus), prescribed medication, or treatment with recombinant human erythropoietin.

Evaluation of health-related quality of life
As assessed by the SF-36 health survey questionnaire, bodily pain and general health showed the worst impairment in the whole study group. Patients with a sleep-related breathing disorder had a significantly lower quality of life in three out of eight subjective measures and in one out of two summary scores (Table 2Go).


View this table:
[in this window]
[in a new window]
 
Table 2.  SF-36 scores in patients with and without sleep-related breathing disorders

 
NHP1 explored six dimensions of perceived health. The worst perceived dimension was sleep, with a median score of 29 (range 0–100). In patients with a sleep-related breathing disorder, only the score ‘emotional reactions’ was significantly worse than in patients without this disorder (27 (0–99) vs 0 (0–27); P=0.01).

To clarify the relationship between sleep-related breathing disorders and quality of life in patients with end-stage renal disease, correlation analyses were performed. The apnoea/hypopnoea index was used as a parameter indicative of the severity of the sleep-related breathing disorder. There were significant correlations between the apnoea/hypopnoea index and the following scores of the SF-36: physical functioning (r=-0.39; P<0.05), social functioning (r=-0.53; P<0.005) (Figure 1AGo), role limitation due to physical problems (r=-0.38; P<0.05), role limitation due to emotional problems (r=-0.41; P<0.05), general health (r=-0.42; P<0.05), vitality (r=-0.39; P<0.05) and physical component summary score (r=-0.46; P<0.05). Furthermore, the apnoea/ hypopnoea index significantly correlated with three of the six dimensions of the NHP1: pain (r=0.38; P<0.05), social isolation (r=0.40; P<0.05) and emotional reactions (r=0.57; P<0.001) (Figure 1BGo). In contrast to the SF-36, correlation coefficients of the Nottingham Health Profile were positive because the two scales run in opposite directions.



View larger version (17K):
[in this window]
[in a new window]
 
Fig. 1.  (A) Social functioning (a measure of the SF-36 health survey questionnaire) plotted against apnoea/hypopnoea index (r=-0.53; P<0.005). (B) Emotional reactions (a measure of the Nottingham Health Profile) plotted against apnoea/hypopnoea index (r=0.57; P<0.001).

 
In addition, multiple stepwise linear regression analysis (‘forward stepwise entry’) was performed with quality of life indicators as the dependent variable and apnoea/hypopnoea index, periodic limb movement index, age, body mass index, months on dialysis, creatinine level, haemoglobin, urea nitrogen, Kt/V, erythropoietin administration, gender and smoking as independent variables. The regression analysis disclosed that the significant correlations between the apnoea/hypopnoea index and most of the scores of the quality of life measures persisted even after correction for the other possible risk factors tested. Table 3Go shows the results of two of the regression studies with emotional reactions (a measure of the Nottingham Health Profile) and social functioning (a measure of the SF-36 health survey questionnaire) as the dependent variables.


View this table:
[in this window]
[in a new window]
 
Table 3.  Factors related to two of the quality of life scores

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Although quality of life has been recognized as an important parameter in evaluating the different forms of renal replacement therapy [2], to our knowledge sleep-related disorders have not yet been addressed in the studies on quality of life in end-stage renal disease. Conversely, in the general population sleep-related disorders have been generally accepted as an important factor influencing quality of life [15]. We therefore felt it necessary to study the impact of sleep-related breathing disorders on quality of life in end-stage renal disease patients, especially as quality of life is often severely limited in these patients.

The most important finding of our study is that sleep-related breathing disorders have a major impact on quality of life in patients with end-stage renal disease. The relationship of the apnoea/hypopnoea index with most of the quality of life measures—even after adjustment for age, gender, body mass index, time on dialysis, haemoglobin and comorbidity—indicates that patients with high apnoea/hypopnoea indices have a worse physical and mental health status than patients on maintenance dialysis without disturbed breathing during the night.

In this context, it has to be acknowledged that the polygraphic studies we performed in our patients tend to underestimate the degree of sleep-related breathing disorders [12]. This is due to the fact that with the POLY-MESAM device the time of sleep cannot be verified. The total recording time may therefore considerably exceed the total sleep time. Since the apnoea/hypopnoea index is calculated using the total recording time in polygraphic recordings, values below the true apnoea/hypopnoea index may have been obtained in those cases where significant periods of wakefulness occurred. The authors are well aware that the relatively small sample size constitutes another limitation of the study, underlining the need for further prospective studies on quality of life issues in patients with end-stage renal disease.

Sleep-related breathing disorders are common in the general population. It is estimated that at least 2–4% of middle-aged adults are affected [16]. The prevalence of disturbed breathing during the night is even higher in patients with end-stage renal disease [6]. The causes of this increased prevalence are unknown, and it is likely that the underlying pathomechanisms differ from those responsible in the general population. It was shown that the total number of disordered breathing events seems not to be acutely altered by conventional haemodialysis treatment [17]. On the other hand, the breathing disorder may resolve after successful kidney transplantation [18]. This suggests that the pathogenesis involves an unstable breathing pattern, possibly caused by an altered metabolic state, uraemia and changes in volume status [18].

Sleep-related breathing disorders are characterized by a recurrent obstruction of the upper airway. This results in episodic oxygen desaturations and disruption of the normal sleep pattern. The majority of patients affected by this disease have symptoms related to poor quality sleep, such as excessive daytime sleepiness and tiredness, lack of concentration and memory impairment. As a result, quality of life in these patients is impaired [15].

Impaired daytime performance and daytime sleepiness are also common symptoms of end-stage renal disease. Thus, in patients receiving maintenance haemodialysis treatment, the symptoms of an associated sleep-related breathing disorder frequently go unreported or may be misdiagnosed as uraemia, depression, chronic illness or insomnia. Nevertheless, sleep-related breathing disorders may have an additional influence on the quality of life in this population, as the results of our study demonstrate. This underlines the need for recording a careful history regarding sleep symptomatology in all patients with chronic renal disease. If necessary, an additional polygraphic or polysomnographic study should be undertaken.

Interestingly, the complaints most heavily noted in end-stage renal disease patients with sleep-related breathing disorders were not obviously related to an impaired nocturnal sleep. Most markedly, social functioning was felt to be impaired, although there is no obvious explanation of why impaired sleep should primarily affect social functioning instead of physical ability. Potentially, it is this peculiar pattern of symptoms that may be responsible for the fact that most patients and their physicians have not recognized a relationship between impaired sleep and reduced quality of life. Social activities may be especially precious to patients and it may be for this reason that the social life subscale provided evidence of the most striking difference across the groups.

It was shown in a study published recently that elimination of sleep-related breathing disorders by treatment with nasal continuous positive airway pressure may result in improvement in quality of life [19]. It remains to be seen whether nasal continuous positive airway pressure is also a potential treatment for sleep apnoea that might preserve quality of life in patients with end-stage renal disease—especially in view of the fact that this treatment modality is much more readily available than renal transplantation as a means of reversing sleep-related breathing disorders.

The present findings may have particular therapeutical implications for those patients who show a severely impaired quality of life, despite the fact that according to the generally accepted parameters the quality of dialysis is good. It is this group that may benefit markedly from therapeutic measures to improve quality of sleep.



   Acknowledgments
 
The POLY-MESAM unit was loaned to the authors by the MAP company (Martinsried, Germany).



   Notes
 
Correspondence and offprint requests to: Prof. Dr Bernd M. Sanner, Department of Medicine I, Marienhospital Hoelkeskampring, Ruhr University Bochum, D-4044625 Herne, Germany. Email: bernd.sanner{at}ruhr\|[hyphen]\|uni\|[hyphen]\|bochum.de Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Lowrie EG, Lazarus JM, Mocelin AJ et al. Survival of patients undergoing chronic hemodialysis and renal transplantation. N Engl J Med1973; 288: 863–867[ISI][Medline]
  2. Evans RW, Manninen DL, Garrison LP et al. The quality of life of patients with end-stage renal disease. N Engl J Med1985; 312: 553–559[Abstract]
  3. Kuhlmann U, Becker HF, Birkhahn M et al. Sleep-apnea in patients with end-stage renal disease and objective results. Clin Nephrol2000; 53: 460–466[ISI][Medline]
  4. Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis1995; 26: 751–756[ISI][Medline]
  5. Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients. Chest1988; 94: 1200–1204[Abstract]
  6. Kimmel PL, Miller G, Mendelson WB. Sleep apnea syndrome in chronic renal disease. Am J Med1989; 86: 308–314[ISI][Medline]
  7. Hunt SM, McKenna SP, McEwen J, Backett EM, Williams J, Papp E. A quantitative approach to perceived health status: a validation study. J Epidemiol Commun Health1980; 34: 281–286.[Abstract]
  8. Kohlmann T, Bullinger M, Kirchberger-Blumstein I. Die deutsche version des Nottingham Health Profile: übersetzungsmethodik und psychometrische Validierung. Soz Präventivmed1997; 42: 175–185
  9. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care1992; 30: 473–483[ISI][Medline]
  10. Brazier JE, Harper R, Jones NMB et al. Validating the SF-36 health survey questionnaire: new outcome measure for primary care. Br Med J1992; 305: 160–164[ISI][Medline]
  11. Mingardi G, Cornalba L, Cortinovis E, Ruggiata R, Mosconi P, Apolone G. Health-related quality of life in dialysis patients. A report from an Italian study using the SF-36 health survey. Nephrol Dial Transplant1999; 14: 1503–1510[Abstract]
  12. Verse T, Pirsig W, Junge-Huelsing B, Kroker B. Validation of the Poly-Mesam seven-channel ambulatory recording unit. Chest2000; 117: 1613–1618[Abstract/Free Full Text]
  13. American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep1999; 22: 667–689[ISI][Medline]
  14. American Sleep Disorders Association Report. Atlas and scoring rules: recording and scoring leg movements. Sleep1993; 16: 748–759[ISI][Medline]
  15. D'Ambrosio C, Bowman T, Mohsenin V. Quality of life in patients with obstructive sleep apnea. Effect of nasal continuous positive airway pressure—a prospective study. Chest1999; 115: 123–129[Abstract/Free Full Text]
  16. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr W. The occurrence of sleep-disordered breathing among middle-aged adults. New Engl J Med1993; 328: 1230–1235[Abstract/Free Full Text]
  17. Mendelson WB, Wadhwa NK, Greenberg HE, Gujavarty K, Bergofsky E. Effects of hemodialysis on sleep apnea syndrome in end-stage renal disease. Clin Nephrol1990; 33: 247–251[ISI][Medline]
  18. Auckley DH, Schmidt-Nowara W, Brown LK. Reversal of sleep apnea hypopnea syndrome in end-stage renal disease after kidney transplantation. Am J Kidney Dis1999; 34: 739–744[ISI][Medline]
  19. Jenkinson C, Davies RJO, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomized prospective parallel trial. Lancet1999; 353: 2100–2105[ISI][Medline]
Received for publication: 24. 2.01
Accepted in revised form: 5. 3.02