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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 378-385
Restless legs syndrome in patients on dialysis


1 Division of Pulmonary/Sleep Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
3 Division of Nephrology, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
4 Division of Nephrology, King Faisal Hospital and Research Center, Jeddah, Saudi Arabia

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   Abstract 

Restless legs syndrome (RLS) is an extremely distressing problem experienced by patients on dialysis; the prevalence appears to be greater than in the general population, with a wide variation from 6.6% to 80%. The diagnosis of RLS is a clinical one, and its definition has been clarified and standardized by internationally recognized diagnostic criteria, published in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). This study was designed to find out the prevalence of RLS in Saudi patients with end-stage renal disease (ESRD) on maintenance dialysis. This is a cross sectional study carried out between May and Sept 2007 at two centers, King Abdulaziz Medical City-King Fahad National Guard Hospital (KAMC-KFNGH), Riyadh and King Faisal Specialist Hospital and Research Centre (KFHRC), Jeddah, Saudi Arabia. Data were gathered on 227 Saudi patients on chronic maintenance hemodialysis or chronic peritoneal dialysis. The prevalence of RLS was measured using IRLSSG's RLS Questionnaire (RLSQ). Potential risk factors for RLS including other sleep disorders, underlying cause of chronic renal failure, duration on dialysis, dialysis shift, biochemical tests and demographic data were also evaluated. The overall prevalence of RLS was 50.22% including 53.7% males and 46.3% females. Their mean age was 55.7 ± 17.2 years and mean duration on dialysis 40.4 ± 37.8 months. Significant predictors of RLS were history of diabetes mellitus (DM), coffee intake, afternoon dialysis, gender and type of dialysis (P= 0.03, 0.01, < 0.001, 0.05 and 0.009 respectively). Patients with RLS were found to be at increased risk of having insomnia and excessive daytime sleepiness (EDS) (P= < 0.001 and 0.001, respectively). Our study suggests that RLS is a very common problem in dialysis population and was significantly associated with other sleep disorders, particularly insomnia, and EDS. Optimal care of dialysis patient should include particular attention to the diagnosis and management of sleep disorders

Keywords: Dialysis, Sleep disorders, Restless legs syndrome

How to cite this article:
Al-Jahdali HH, Al-Qadhi WA, Khogeer HA, Al-Hejaili FF, Al-Ghamdi SM, Al Sayyari AA. Restless legs syndrome in patients on dialysis. Saudi J Kidney Dis Transpl 2009;20:378-85

How to cite this URL:
Al-Jahdali HH, Al-Qadhi WA, Khogeer HA, Al-Hejaili FF, Al-Ghamdi SM, Al Sayyari AA. Restless legs syndrome in patients on dialysis. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2014 Nov 27];20:378-85. Available from: http://www.sjkdt.org/text.asp?2009/20/3/378/50760

   Introduction Top


End stage renal disease (ESRD) is a signi­ficant problem in the Kingdom of Saudi Arabia (KSA) with a reported prevalence of 139 per million population. [1] The number of patients re­ceiving hemodialysis (HD) therapy in KSA has increased by approximately 10 to 15 fold in recent years and the estimated annual increase is about 8.6%. [2],[3] Restless legs syndrome (RLS) is a neu­rological disorder, defined by the International Classification of Sleep Disorders as "a disorder characterized by disagreeable leg sensations, usually prior to sleep onset, that cause an al­most irresistible urge to move the legs". Often, the uncomfortable sensations are described as creeping, crawling, tingling, aching, burning, pulling, itching, or cramping. [4] These symptoms may be particularly bothersome during dialysis. [5] Symptoms often result in disrupted sleep and excessive daytime sleepiness (EDS). The preva­lence of RLS in the general population is estimated to be between 5 and 15%. [4] Its preva­lence in the dialysis population appears to be greater than in the general population, although there is wide variation among different popu­lations with rates quoted from 6.6% to 80%. [5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] The diagnosis of RLS is a clinical one, and its definition was clarified and standardized by in­ternationally recognized diagnostic criteria, pu­blished by the International Restless Legs Syn­drome Study Group (IRLSSG) in 1995. [21] This classification received wide acceptance only recently with the validation of rating scale for RLS. [22] It is interesting that several studies looking at risk factors of underlying etiology for RLS in dialysis patients have been performed in recent years and the results are conflicting. Anemia, serum ferritin, serum iron, calcium, phosphorus, creatinine and urea levels have all been blamed in the causation of RLS in dialysis patients. [6],[16],[23],[24],[25]

However, recent studies have failed to demon­ strate such correlation. [11],[12],[13],[16],[17],[19]

Symptoms of restless legs were independently associated with diminished quality of life and increased mortality. [5],[18],[26],[27] Restless legs syndrome is also associated with other sleep disorders such as insomnia and EDS. [6],[10],[18],[28],[29]

This study is designed to find out the preva­lence of RLS in Saudi patients with ESRD on maintenance dialysis and to delineate associated clinical and biomedical parameters, which may be linked to this syndrome.


   Methodology Top


We conducted an observational cross-sectional study from May to September 2007 at the King Abdulaziz Medical City-King Fahad National Guard Hospital (KAMC-KFNGH), Riyadh and King Faisal Specialist Hospital and Research Centre (KFHRC), Jeddah, KSA. This study was approved by the research and ethics committee at the King Abdulaziz Medical City King Fahad National Guard Hospital (KAMC-KFNGH), Ri­yadh. We enrolled all stable patients on chronic dialysis in both institutions. We excluded con­fused, demented patients and patients who refused to participate and sign the written consent. The data collection was carried out by personal interview by two of the authors (WQ and HK), using a structured questionnaire. These questionnaires were adopted from validated in­ternational questionnaires and are used rou­tinely at our sleep disorders center. Data collected included age, gender, level of edu­cation, marital status, employment, past medi­cal history, medication, smoking and coffee intake, the underlying cause of chronic renal failure, duration on dialysis, dialysis shift, hemogram, serum ferritin, serum urea, calcium and phosphate as well as dialysis adequacy (Kt/V). We used the four questions proposed by the IRLSSG for the clinical diagnosis of RLS. [22] Patients were also asked about symptoms of insomnia, using five validated questions. [30] Ad­ditionally, patients were asked about symptoms of excessive day time sleepiness using Epworth Sleeping Scale (ESS) where a score of more than 10 indicates increased sleepiness. Pitts­burgh Sleep Quality Index (PSQI) was used to assess sleep quality (score more < 5 indicate good sleep quality). Data were summarized as mean ± standard deviation or number and percent, as appropriate. To assess the possible influence of demographic and other variables on prevalence of RLS, we used un-paired t-test and the Mann-Whitney U-test for non para­metric data, where appropriate. A P value of less than 0.05 was considered significant. Sta­tistical analysis were carried out using SPSS version 13 software.


   Results Top


The total number of patients recruited for the study was 227. The mean age was 55.7 ± 17.2 years. There were 122 males (53.7%) and 105 females (46.3%). The mean duration on dialysis was 40.4 ± 37.8 months. The commonest cause of renal failure was diabetes mellitus (DM) (52%). The majority of patients (80%) had less than high school education and 50.7% were employed. The mean BMI was 26.7 ± 6.4.with 56% of the patients either overweight or obese. The most common medications used were ery­thropoietin, iron supplements, vitamins, and anti­hypertensive drugs. Other demographic data and co-morbidities are shown in [Table 1].

The total number of patients who met all cri­teria for the diagnosis of RLS was 114, giving a prevalence of 50.22%. When patients with RLS were compared to those without, there was no difference concerning age, BMI, iron, hemoglo­bin, ferritin, calcium and phosphorus. Also, there was no significant correlation between RLS and duration or adequacy of dialysis, as measured by Kt/V index. There were significant positive correlations with female gender, history of DM, coffee intake (daily and regular use), afternoon dialysis, peritoneal dialysis and RLS; (P= 0.05, 0.03, 0.01, < 0.001, and 0.009), respectively. The data are summarized in [Table 1] and [Table 2].

Patients with RLS were also compared to controls in relation to sleep quality using PSQI, insomnia level and to excessive daytime sleepi­ness using ESS and risk for obstructive sleep apnea syndrome using Berlin questionnaires. There was no significant difference in sleep qua­lity. However, patients with RLS had more insomnia, excessive daytime sleepiness and high risk for obstructive sleep apnea syndrome (OSAS) (P= < 0.001, 0.001, 0.001) respectively, as shown in [Table 3].

Using the IRLSSG criteria for the diagnosis of RLS, the reported prevalence of RLS among dialysis patients ranged from 6 to 68%. [Table 4] compares the prevalence of RLS in our study to other studies that used the IRLSSG criteria.


   Discussion Top


This is the first study describing RLS in a large Saudi dialysis population. Our study has shown that RLS is common (prevalence 50.22%) and more in women and diabetic patients. We also found a significant correlation between RLS and HD, coffee consumption and afternoon dia­lysis. Moreover, our study also confirms that RLS in dialysis patients is associated with other sleep disorders such as insomnia and EDS. The pre­valence of RLS is reported to be between 5 and 15% in the general population and 6 to 80% in patients with chronic renal failure. [4],[6],[7],[8],[9],[31] The two major reasons for this variability are the number of patients studied and the different criteria used to diagnose RLS. When we com­pare our study to other studies that used the IRLSSG criteria, [21] we still find significant di­fferences. The prevalence of RLS was 50.22% in our study, 6% in the Indian population [31] 62% in the Chinese population, [7],[8] 12-23% in Japa­nese, [16],[20] and 20-45% in Caucasians. [5],[11],[12],[13],[14],[15],[18],[19] This suggests that genetic differences may be another reason for the wide variation reported in the prevalence of RLS. [32]

It is important to note, however, that the mean age in the Indian study was 34.5 ± 11.1 years whereas our patients were older with a mean age of 57.12 ± 16.58 years. More than 96% of our patients are on regular erythropoietin and iron supplements. Anemia, iron deficiency and serum calcium level have all been linked to RLS; however, more recent studies have failed to confirm those earlier findings. [12],[26] Similar to other studies, in our study, RLS was not asso­ciated with the hemoglobin level, the presence of iron deficiency (assessed by serum ferritin), calcium, and phosphorus level or dialysis dura­tion.[7],[10],[12],[26],[33]. However, we found that RLS was more frequent in female patients. Several stu­dies have also found females to have a higher prevalence of RLS. [19],[23],[24],[34],[35],[36],[37] This association may be related to the secretion of sex hormones following circadian rhythms. [19]

Chen et al in their study, [33] found that smoking was associated with RLS/PLM, whereas con­sumption of coffee and tea had a negative effect on RLS/PLM. [33] However, Lutz E et al reported a significant correlation between RLS and co­ffee intake. [38] Gigli et al, did not find any asso­ciation between smoking, coffee intake and RLS. [11] In our study, we found significant cor­relation between RLS and daily regular use of coffee, but not with cigarette smoking.

Similar to findings from other studies, we found no significant correlation between the PSQI (which measures sleep quality) and RLS. However, there were significant differences in the excessive daytime sleepiness (ESS more than 10) and insomnia (P= < 0.001 and 0.001, respectively). The association between RLS and insomnia in patients on maintenance dialysis has been reported previously. [21],[28],[30],[39] In our study, patients with RLS had higher incidence and severity of clinically significant insomnia as compared to dialysis patients without RLS.

The main strengths of this study include the large number of patients studied and the com­prehensive, standards based professional inter­view process. This, to the best of our knowledge, is the first such study in Saudi dialysis patients. One weakness of this study, which should be addressed in the future, is that we did not examine the patients for evidence of diabetic neuropathy, which may contribute to the seve­rity of RLS. In diabetic patients, polyneuro­pathy represents the main risk factor for RLS. However, polyneuropathy only partially explains the increased prevalence of RLS in type 2 dia­betics. [40],[41] Notwithstanding this fact, it is surpri­sing, important and inte-resting to note that the number of diabetics in the RLS group was only slightly higher than that in the non RLS group, (68/114 versus 51/113 (P= 0.03) suggesting that diabetes, while possibly contributing to the risk of RLS, was not a strong independent risk fac­tor for RLS.

Assessment of adequacy of dialysis is a central issue in the management of patients undergoing dialysis. Simply following the blood urea nitro­gen (BUN) is insufficient because a low BUN can reflect inadequate nutrition rather than sufficient dialytic urea removal. Kt/V is accep­ted as the optimal method for assessing the adequacy of dialysis. Inadequate dialysis (lower level of Kt/V) was associated with RLS. [33] How­ever, this was not confirmed by other studies. [10] We did find significant correlation between Kt/V and RLS. We did not find any association between RLS and dialysis duration. However, patients with afternoon dialysis had more RLS and insomnia (data not shown) than any other shift. This difference in the effect of dialysis shift may relate to sleep schedules in different societies. In Saudi Arabia, it is a common habit among many people, particularly unemployed individuals, to take afternoon naps; in our study, only 50.7% of the patients were employed. Thus, many patients with RLS may be deprived of their afternoon naps and this may lead to the feeling of insomnia/sleepiness, and general fa­tigue/tiredness. This finding has not been con­firmed by other studies. [33],[42]


   Conclusion/Recommendations Top


By using the IRLSSG questionnaire to identify dialysis patients with RLS, the prevalence was significantly high. RLS was significantly asso­ciated with other sleep disorders, particularly insomnia and daytime sleepiness. These sleep disorders may result in poor quality of life and may lead to more medical complications. There­fore, physicians taking care of dialysis patients should be aware of these sleep disorders. Fur­ther studies are needed to rule out sleep brea­thing disorders as a cause of excessive day-time sleepiness. Additionally, all future studies of RLS should include evaluation of diabetic neuropa­thy (ideally using nerve conduction studies) to determine if this is an additional risk factor for RLS and if the degree of neuropathy affects the severity of RLS.

 
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Correspondence Address:
Hamdan H Al-Jahdali
Head of Pulmonary/Sleep Disorder Division, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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