Key-words:
Excessive daytime sleepiness - hemodialysis - insomnia - restless legs syndrome -
sleep apnea - sleep disorders
Introduction
Patients with chronic renal disease, and in particular chronic hemodialysis patients,
are prone to various sleep disorders (SDs) that may affect their daily quality of
life and contribute to increased their cardiovascular morbidity and mortality.[[1]] In comparison to the general population, the prevalence of SDs in patients with
renal impairment is significantly increased due to the presence of usual risk factors
such as age, gender, obesity and other factors specific to uremia and dialysis (anemia,
uremic toxins, inflammation, side effects of drugs).[[2]]
Sleep disorders appear very early during stages 1 and 2 of chronic renal failure and
may worsen with decreasing renal function.[[2]]
It's reported in other studies that up to 80% of dialysis patients complain of poor
quality of sleep.[[3]]
Insomnia, sleep apnea, restless legs syndrome and excessive daytime sleepiness are
the most commonly reported SDs.[[4]] Besides, studies have shown that SDs may increase the risk of cardiovascular death
in patients with chronic renal failure.[[3]]
Patients and Methods
The study was designed as prospective observational single-center study conducted
in the renal nephrology and renal transplant department of the Mohammed V Military
Training Hospital in Rabat. All the 52 chronic hemodialysis patients were recruited
for this study. The inclusion criteria were: adult dialysis patients (over 18 years
of age), chronic hemodialysis patients for more than 1 year, three sessions per week,
4 h each. In the included patients, the SDs studied were: Insomnia, sleep apnea syndrome
(SAS), restless legs syndrome and excessive daytime sleepiness.
We conducted this study using a questionnaire in French and/or translated into dialectal
Arabic, and based on the Insomnia Severity Index questionnaire which contains seven
questions (difficulty falling asleep, difficulty staying asleep or waking too early
in the morning etc.) whose answers are noted from 0 to 4, the sum of the scores obtained
forming a score that can vary between 0 and 28. The risk of SAS was estimated with
the non obstructive sleep apnea syndrome (NoSAS) score, which represents the weighted
sum of the points attributed to the following five parameters: The choker, the body
mass index, the snoring, the age, and the male sex. The maximum score is 17 points,
and a threshold of ≥8 is associated with a high risk of sleep-disordered breathing.[[4]]
Restless Legs Syndrome (RLS) was assessed by the abridged version of the Cambridge-Hopkins
RLS questionnaire analyzing 13 symptom intensity and frequency.[[5]] Excessive daytime sleepiness is evaluated by the Epworth Sleepiness Scale, which
is a simple way to detect pathological daytime sleepiness and has eight questions,
a total of more than 10 points suggesting the presence of pathological somnolence.[[4]]
In addition, clinical parameters (age, sex, medical history, smoking and alcohol consumption,
underlying renal disease, blood pressure, temperature, dry weight), biochemical measurements
(creatinine, urea, hemoglobin, fasting glucose, albumin C-reactive protein, calcemia,
phosphatemia, and PTH 1–84) and dialysis metrics (frequency and duration of the dialysis
session, dry weight, interdialytic weight gain, mean Kt/v) were collected from the
medical records of the patients.
Descriptive and deductive statistical analyzes were performed with SPSS 18.0 software
(SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0, SPSS Inc., Chicago,
IL, USA). The data are expressed as mean ± standard deviation or interquartile median
interval or percentage according to their nature and distribution. The prevalence
of each standard deviation has been estimated. The univariate and multivariate logistic
regression analysis was used to identify the risk factors associated with different
disorders. Insomnia, SAS and restless legs syndrome were considered independent variables
and a model was constructed for each of them to identify the co-variables associated
with each SD. Excessive daily sleepiness is common consequences of these SDs and was
not considered a dependent variable in the multivariate analysis. The difference is
considered statistically significant for P < 0.05. At the end of this statistical
analysis, we will highlight the factors associated with the onset of these SDs.
Results
Fifty-two patients with the mean age of patients were 50 years ± 17 years with extremes
ranging from 24 to 76 years were included in this study. The sex ratio (male/female)
was 1.1. Mean dialysis duration was 60 ± 17 months. Cause of end-stage renal disease
was unknown in 48% of cases, glomerulonephritis in 21% of cases, a tubulointerstitial
disease in 12.8%, diabetes in 10.2% of cases and vascular disease in 8% of cases.
The clinical, biochemical and dialytic characteristics of patients are shown in [[Table 1]]. SDs were found in 40 patients (76.9%) with a predominance of insomnia (52%) and
SAS (43%), excessive daytime sleepiness was found in 40% of patients and restless
leg syndrome in 35% of patients. SDs were more common in patients between the ages
of 40 and 60 (56%), 20% of patients were between 24 and 40, and 24% of patients were
over 60 years old. The causes attributed to insomnia were chronic nocturnal pain in
63% of patients with an osteoarticular and neurological origin, anxiety in 21% of
cases and depression in 16% of cases.
Table 1: Demographic, anthropometric, laboratory and dialysis characteristics of the population
study
In univariate statistical analysis, the factors statistically correlated with the
onset of insomnia are anemia and excessive daytime sleepiness [[Table 2]]. SAS is associated with older age, obesity and excessive daytime sleepiness. Restless
legs syndrome has shown a significant association with advanced age, anemia and the
presence of a biological inflammatory syndrome.
Table 2: Univariate analysis of factors associated with sleep disorders
However, multivariate analysis identified anemia, excessive daytime sleepiness, and
inflammation as factors associated with insomnia [[Table 3]]. Age ≥50 years, obesity and excessive daytime sleepiness also correlated with SAS.
Restless legs syndrome is associated with advanced age, excessive daytime sleepiness
and the presence of a biological inflammatory syndrome. Other parameters such as sex,
dialysis quality, arterial hypertension, diabetes, hypoalbuminemia, and interdialytic
weight gain did not show a significant association with any of the SDs studied. None
of our patients was followed or under specific treatment for these SDs.
Table 3: Multivariate analysis of factors associated with sleep disorders
Discussion
This study confirms that SDs are widespread in chronic dialysis patients. The prevalence
in our series was close to that reported in Asian or European patients ranging from
41% to 86%.[[5]],[[6]] These disorders were dominated by insomnia and SAS, consistent with literature
data.[[4]] Restless legs syndrome and excessive daytime sleepiness were present in 35% and
40% of our patients respectively, contrasting with the low frequency reported in African-American
patients.[[7]]
Chronic insomnia (>6 months) is classified as primary and secondary. In secondary
causes, for example, there are chronic pains or the syndrome of muscular impatiences
of the lower limbs preventing patients from sleeping at night. This disorder may also
be primary with difficulty initiating and maintaining sleep during the night without
apparent cause. A condition of “hyper-arousal” that affects sleepiness and sleep maintenance
is then suspected. Sleep-wake disorders are also well-known in dialysis patients and
would be secondary to dysregulation of melatonin secretion.[[8]]
SAS is characterized by repeated stops of night breathing secondary to partial pharyngeal
(hypopnea) or complete (apnea) collapse.[[9]] It has been selected in several studies as an independent risk factor for morbidity
and cardiovascular mortality in this population.[[10]] Obstructive SAS is the most common type in the general population, whereas central
or mixed type SAS are more common in chronic kidney disease patients.[[11]]
Restless legs syndrome is an imperative need to move the legs, accompanied by unpleasant
sensations in the legs relieved to movement, which occur at rest, usually in the evening
or at night. This syndrome is associated in 80% of the cases with periodic stereotyped
and repetitive movements of the lower limbs occurring during sleep. They can disrupt
sleep and cause daytime sleepiness in severe cases.[[12]] It is thought to be due to dysfunction of the dopaminergic system associated with
cerebral iron deficiency with a disturbance of the iron permeability of the blood-brain
barrier, without a direct relationship with plasma ferritin level[[13]] Dialysis patients frequently fall asleep during dialysis sessions and often experience
excessive sleepiness during the day.[[5]],[[14]]
Many factors such as diabetes, chronic renal failure neuropathy, uremia, psychiatric
disorders, malnutrition, and anemia have been identified as associated with SDs in
chronic hemodialysis patients.[[15]],[[16]],[[17]],[[18]] In some studies, the low level of physical activity has been statistically significantly
associated with insomnia.[[19]] Besides, some authors have investigated the seasonal rhythm of SDs in hemodialysis.[[20]] Nevertheless, in some studies, SDs do not appear to be related to biological data
or dialysis parameters suggesting the involvement of disorders. Anxio-depressive in
the genesis of these SDs.[[19]]
In our study, anemia and inflammation were associated with SDs; advanced age and obesity
were associated with SAS. Advanced age and the presence of a biological inflammatory
syndrome were associated with restless legs syndrome while excessive daytime sleepiness
was correlated with all other SDs.
Our results confirm previous scientific data on SDs in chronic hemodialysis patients.
Some variations are not explained by the clinical and biological data they are probably
due to cultural characteristics that we do not understand yet.[[21]]
Despite the interesting results, our study has some limitations due primarily to its
small sample size, the evaluation of SDs being based on questionnaires in the absence
of para-clinical exams might not be able to estimate the prevalence of these SDs,
and finally, despite the associated factors, no causal effect can be formally confirmed.
The development of repeated epidemiological surveys may help to better understand
the prevalence of SDs in chronic hemodialysis patients in Morocco. Prevention and
care programs in Morocco must take into account all relevant structural, clinical,
biological, and psychosocial determinants to promote more personalized prevention
programs.
Conclusions
SDs are common in hemodialysis patients. They seem to be related to clinical, biological,
dialytic and psychological factors. Early diagnosis is necessary to offer multidisciplinary
care between nephrologists, psychiatrists, cardiologists, and neurologists.
Author's contribution
WA: Conception and realization of the study and drafting of the article. FL, AO and
DEK Critical review and revision of the manuscript. All authors approved the final
version.
Compliance with ethical principles
Ethical approval was granted by the Research Ethics Committee of the faculty of Medicine
and Pharmacy, Mohammed V University, Rabat– Morocco and all participants provided
verbal informed consent.
Reviewers:
Khalid Akkari (Dammam, Saudi Arabia)
Siddiq Anwar (Abu Dhabi, UAE)
Editors:
Salem A Beshyah (Abu Dhabi, UAE)
Elmahdi A Elkhammas (Columbus OH, USA)
