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| RENAL DATA FROM THE ARAB WORLD || |
|Year : 2011 | Volume : 22 | Issue : 2 | Page : 368-372 |
|Restless legs syndrome in patients on hemodialysis |
Saleh Mohammad Yaser Salman
Department of Internal Medicine, Faculty of Medicine, Aleppo University, Allepo, Syria
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|Date of Web Publication ||18-Mar-2011 |
| Abstract || || |
Restless legs syndrome (RLS) is common among dialysis patients, with a reported prevalence of 6-60%. The prevalence of RLS in Syrian patients on hemodialysis (HD) is not known. The purpose of this study is to determine the prevalence of RLS in patients on regular HD, and to find the possible correlation between the presence of RLS and demographic, clinical, and biochemical factors. One hundred and twenty-three patients (male/female = 70/53, mean age = 41.95 ± 15.11 years) on HD therapy at the Aleppo University Hospital were enrolled into the study. RLS was diagnosed based on criteria established by the International Restless Legs Syndrome Study Group (IRLSSG). Data procured were compared between patients with and without RLS. Applying the IRLSSG criteria for the diagnosis, RLS was seen in 20.3% of the study patients. No significant difference in age, gender, and intake of nicotine and caffeine was found between patients with and without the RLS. Similarly, there was no difference between the two groups in the duration of end-stage renal disease (ESRD), the period of dialysis dependence, dialysis adequacy, urea and creatinine levels, and the presence of anemia. The co-morbidities and the use of drugs also did not differ in the two groups. Our study suggests that the high prevalence of RLS among patients on HD requires careful attention and correct diagnosis can lead to better therapy and better quality of life. The pathogenesis of RLS is not clear and further studies are required to identify any possible cause as well as to discover the impact of this syndrome on sleep, quality of life, and possibly other complications such as cardiovasculare disease.
|How to cite this article: |
Salman SY. Restless legs syndrome in patients on hemodialysis. Saudi J Kidney Dis Transpl 2011;22:368-72
| Introduction || || |
The restless legs syndrome (RLS) is one of the most unpleasant complaints in patients undergoing chronic hemodialysis (HD). The patients suffer from paresthesias or a burning sensensation, sometimes amounting to severe pain that usually affects the legs, but rarely the arms. The symptoms are observed only at rest and are most pronounced in the evening and night. The patients feel an urge to move the limbs, with which they experience a short relief.
The prevalence of RLS in uremic patients is estimated to range between 6 and 60%.  Although this syndrome is frequent among dialysis patients, RLS often remains undiscovered because the symptoms may not be recognized as a typical clinical entity. Treatment with dopaminergic agents, , clonazepam, , anticonvulsants,  or clonidine,  has been reported to be effective in these patients.
The underlying cause of RLS, however, remains to be identified. There is some support from neurophysiological studies and neuroimaging that RLS is sub-cortically generated in reticular neuron populations.  Pharmacological studies show some evidence for the involvement of the dopaminergic and opiate systems of the central nervous system in the pathogenesis of RLS.  The pathophysiological relationship between the occurrence of RLS and chronic renal failure is still unclear. Previous hypotheses assume that anemia could play a major role in the development of uremic RLS. ,
In this study, our first objective was to estimate the prevalence of RLS in chronic HD patients, according to the standardized diagnostic criteria for RLS. Secondly, by analyzing the biochemical data, we hoped to be able to differentiate uremic patients with RLS from those without RLS to further elucidate the pathophysiological mechanisms present in uremic RLS patients. Lastly, we documented the clinical history and the medication administered during the time of investigation.
| Subjects and Methods || || |
Between April 2008 and May 2009, all stable chronic HD patients treated at the Aleppo University Hospital, using similar dialysis techniques, were interviewed. The main criteria elaborated by the International Restless Legs Syndrome Study Group (IRLSSG)  served as a guideline to diagnose RLS. The four minimal criteria included: (a) a desire to move the limbs, usually associated with paresthesias or dysesthesias; (b) motor restlessness; (c) an aggravation or exclusive presentation of symptoms at rest with complete or partial relief by activity; and (d) an aggravation of symptoms in the evening or night.
Clinical history including age, duration of uremia, actual time on dialysis, additional diseases and current therapy was recorded. The medications administered were divided into pharmacological sub-groups including erythro-poietin, iron supplementation, phosphate binders (calcium carbonate), beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, diuretics, antidiabetics, nitrates, and calcitriol.
During the survey, biochemical analyses were performed in all patients as follows: hemoglobin, hematocrit, white blood cell count, platelet count, urea (before and after dialysis) and creatinine (before and after dialysis); all biochemical analyses were performed 10-15 minutes before the dialysis session.
Finally, the study patients were classified into three groups:
Group-1: "Definitive RLS": Patients who fulfilled all four diagnostic criteria of the IRLSSG
Group-2: "Questionable RLS": Patients who fulfilled three of the four diagnostic criteria of the IRLSSG
Group-3: "Non-RLS": Patients who fulfilled less than three of the four diagnostic criteria of the IRLSSG
| Statistical Analysis || || |
Data were entered into Microsoft Excel spreadsheet. Statistical analysis was performed using the SPSS software version 12. Mean and standard deviation were calculated for all continuous variables. Patients on HD with and without RLS were compared on categorical variables using Pearson's chi-square and on continuous variables using the Student's t-test or one-way analysis of variance (ANOVA). Value of P < 0.05 was considered as statistically significant.
| Results || || |
All the 123 patients (70 males, 53 females) on HD at our dialysis center participated in the study. The mean age was 41.59 ± 15.11 years, and the mean duration the patients had been on dialysis was 49.39 ± 30.40 months.
Twenty-five patients (20.33%) fulfilled the diagnostic criteria for RLS (Group 1), five patients (4.06%) had questionable RLS, and 93 patients (75.61%) did not have any features
suggestive of RLS. The mean age of Group-1, "definitive RLS", patients was 44.56 ± 15.50 years and that of Group-3, "non-RLS", patients was 40.39 ± 15.03 years (P = 0.246). The duration on dialysis did not differ significantly between Group-1 and Group-3 (54.24 ± 28.2 vs. 49.52 ± 31.13 months, P = 0.107). The demographic data of patients in Group-1 and Group-3 are shown in [Table 1].
| ||Table 1: Demographic data of patients with and without the restless legs syndrome. |
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Six patients (24%) in Group-1 and 19 patients (20.5%) in Group-3 had diabetes mellitus; 12% of the patients in Group-1 and 10.8% of the patients in Group-3 had coronary artery disease; 72% of the patients in Group-1 and 69.9% of the patients in Group-3 had arterial hypertension; 16% of the patients in Group-1 and 19.4% of the patients in Group-3 were positive for hepatitis C virus antibody; and neurological manifestations such as stroke or transient cerebral ischemia were present in two patients (8%) of Group-1 and five patients (5.4%) of Group-3. The mean duration of actual dialysis per week was 8.26 ± 1.46 hours in Group-1 and 8.12 ± 1.24 hours in Group-3 (P = 0.815).
No statistical differences were found in the current medication during the period of study.
The results of the biochemical analysis among patients in Group-1 and Group-3 are shown in [Table 2]. None of the biochemical parameters investigated differed significantly between the two groups.
| ||Table 2: Results of biochemical analysis in patients with and without restless legs syndrome. |
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| Discussion || || |
The estimated prevalence of RLS in uremic patients or in patients on dialysis varies from 6 to 60%.  Such high degree of variability depends in part on the wide variation in the number of patients in these studies, different dialysis strategies used as well as the diagnostic criteria applied in the studies.
In our case series, using the strict IRLSSG criteria, we found a prevalence of 20.33%, similar to the 23% reported by Collado-Seidel et al  and to 21.5% reported by Gigli et al,  but higher than the 12.2% reported by Takaki et al.  However, 4.5% "potential" RLS should be included in the latter series, which comprised a group of patients without symptoms of RLS, but who were receiving dopaminergic agents.
In our study, the prevalence of RLS was not significantly correlated to age, and we did not find a significant gender difference between patients with and without RLS.
The pathophysiology of the RLS is still unclear. In patients on dialysis, it has been suggested that anemia may play a major part in the development of RLS.  This association is thought to exist in other symptomatic forms of RLS, such as iron deficiency anemia and pregnancy, as well. ,, In an earlier study on 55 uremic patients, Roger et al  suggested a relationship between low hemoglobin values and the occurrence of symptoms of RLS. In our study, we failed to find any correlation between the hemoglobin or hematocrit values and the presence of RLS in patients on HD.
The association between RLS and duration on dialysis (dialysis dependence) remains controversial. In our study, duration on dialysis did not differ significantly between patients with and without RLS. This result was similar to those of Collado-Seidel et al,  but dissimilar to the results of Gigli et al. 
The symptoms of RLS were found to be related to urea and creatinine levels in the study of Walker et al,  but no such correlation was found in other studies. ,, In our study, urea and creatinine levels, as well as dialysis adequacy did not differ significantly between patients with and without RLS. Similarly, no significant correlation was found between any other biochemical parameters and the presence of RLS.
No association has been found between the presence of RLS and other co-morbidities such as coronary artery disease, diabetes, stroke, transient ischemic attack, or hepatitis; this is similar to the results of Collado-Seidel,  and Gigli et al. 
Thus, we could not find any possible correlation between the occurrence of RLS and any of the mentioned demographic data, the co-morbidities, current drugs or biochemical parameters.
| Conclusions || || |
Our study suggests that RLS is very frequent among patients on HD. It is unclear which factors of dialysis, if any, are implicated in the development of RLS in uremic patients. Patients with RLS are associated with a higher frequency of insomnia and a higher prevalence of symptoms suggesting other sleep disorders. Considering that sleep deprived patients are at risk for immunological and cardiovascular diseases,  disturbed sleep can be an important factor in reducing the life expectancy of patients with end-stage renal disease (ESRD). 
However, in our study, we did not focus on the impact of RLS, and further studies are required. Also, the high prevalence of RLS among uremic patients requires careful investigation, and correct identification of these disorders can lead to better therapy and improvement of the clinical condition and quality of life.
| References || || |
|1. ||Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis 2004;43:43. |
|2. ||Sandyk R, Bernick C, Lee SM, Stern LZ, Iacono RP, Bamford CR. L-dopa in uremic patients with the restless legs syndrome. Int J Neurosci 1987;35:233-5. |
|3. ||Walker SL, Fine A, Kryger MH. L-dopa/carbidopa for nocturnal movement disorders in uremia. Sleep 1996;19:214-8. |
|4. ||Read DJ, Feest TG, Nassim MA. Clonazepam: Effective treatment for restless legs syndrome in uremia. Br Med J 1981;283:885-6. |
|5. ||Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi E. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand 1984;69:428-30. |
|6. ||Thorp M, Morris C, Bagby S. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis 2001;3 8: 104-8. |
|7. ||Bastani B, Westerwelt FB. Effectiveness of clonidine in alleviating the symptoms of "restless legs". Am J Kidney Dis 1987;10:326 . |
|8. ||Trenkwalder C, Bucher S, Oertel WH, Proeckl D, Plendel H, Paulus W. Bereitschaftspotential in idiopathic and symptomatic restless legs syndrome: Electroencephalogram. Clin Neurophysiol 1993;89:95-103. |
|9. ||Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol 1997;41:639-45. |
|10. ||Nordlander NB. Therapy in restless legs. Acta Med Scand 1953;145:453-7. Legs syndrome. Int J Neurosci 1987;35:233-5. |
|11. ||Roger SD, Harris DC, Stewart JH. Possible relation between restless legs and anemia in renal dialysis patients. Lancet 1991;1:1551. |
|12. ||Walters A; the International Restless Syndrome Legs Study Group. Toward a better definition of the restless legs syndrome. Mov Disord 1995;10:634-42. |
|13. ||Collado-Seidel V, Kohnen R, Samtleben W, et al. Clinical and biochemical findings in uremic patients with and without restless legs syndrome. Am J Kidney Dis 1998;31:324-8. |
|14. ||Gigli GL, Adorati M, Dolso P, et al. Restless legs syndrome in end-stage renal disease. Sleep Med 2004;11:309-15. |
|15. ||Takaki J, Nishi T, Nangaku M, et al. Clinical and psychological aspects of restlesslegs syndrome in uremic patients on hemodialysis. Am J Kidney Dis 2003;41:833-9. |
|16. ||Ekbom KA. Restless legs syndrome. Neurology 1960;10:868-73. |
|17. ||Fonseca A, Beswick DT, Blake DR. Restless legs syndrome: The influence of iron on its pathogenesis and treatment. European Iron Club 1988; Frankfurt [abstract]. |
|18. ||Nilsson PM, Nilsson A, Hedblad B, Berglund G. Sleep disturbance in association with elevated pulse rate for prediction of mortality- consequences of mental strain? J Intern Med 2001;250:521-9. |
|19. ||Walker SL, Fine A, Kryger MH. Sleep complaints are common in dialysis unit. Am J Kidney Dis 1995;26:751-6. |
Saleh Mohammad Yaser Salman
Department of Internal Medicine, Faculty of Medicine, Aleppo University, Allepo
[Table 1], [Table 2]
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