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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2011  |  Volume : 22  |  Issue : 2  |  Page : 368-372
Restless legs syndrome in patients on hemodialysis

Department of Internal Medicine, Faculty of Medicine, Aleppo University, Allepo, Syria

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Date of Web Publication18-Mar-2011


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

How to cite this URL:
Salman SY. Restless legs syndrome in patients on hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2021 Dec 6];22:368-72. Available from: https://www.sjkdt.org/text.asp?2011/22/2/368/77649

   Introduction Top

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%. [1] 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, [2],[3] clonazepam, [4],[5] anticonvulsants, [6] or clonidine, [7] 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. [8] Pharmaco­logical studies show some evidence for the involvement of the dopaminergic and opiate systems of the central nervous system in the pathogenesis of RLS. [9] 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. [10],[11]

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 Top

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) [12] 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 Top

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 Top

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 Top

The estimated prevalence of RLS in uremic patients or in patients on dialysis varies from 6 to 60%. [1] 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 [13] and to 21.5% reported by Gigli et al, [14] but higher than the 12.2% reported by Takaki et al. [15] 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. [11] This association is thought to exist in other symptomatic forms of RLS, such as iron deficiency anemia and pregnancy, as well. [10],[16],[17] In an earlier study on 55 uremic patients, Roger et al [11] 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, [13] but dissi­milar to the results of Gigli et al. [14]

The symptoms of RLS were found to be re­lated to urea and creatinine levels in the study of Walker et al, [3] but no such correlation was found in other studies. [13],[14],[15] 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, [13] and Gigli et al. [14]

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 Top

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, [18] disturbed sleep can be an important factor in reducing the life expectancy of pa­tients with end-stage renal disease (ESRD). [19]

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 Top

1.Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis 2004;43:43.  Back to cited text no. 1
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.  Back to cited text no. 2
3.Walker SL, Fine A, Kryger MH. L-dopa/carbi­dopa for nocturnal movement disorders in uremia. Sleep 1996;19:214-8.  Back to cited text no. 3
4.Read DJ, Feest TG, Nassim MA. Clonazepam: Effective treatment for restless legs syndrome in uremia. Br Med J 1981;283:885-6.  Back to cited text no. 4
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.  Back to cited text no. 5
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.  Back to cited text no. 6
7.Bastani B, Westerwelt FB. Effectiveness of clonidine in alleviating the symptoms of "rest­less legs". Am J Kidney Dis 1987;10:326 .  Back to cited text no. 7
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.  Back to cited text no. 8
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.  Back to cited text no. 9
10.Nordlander NB. Therapy in restless legs. Acta Med Scand 1953;145:453-7. Legs syndrome. Int J Neurosci 1987;35:233-5.  Back to cited text no. 10
11.Roger SD, Harris DC, Stewart JH. Possible relation between restless legs and anemia in renal dialysis patients. Lancet 1991;1:1551.  Back to cited text no. 11
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.  Back to cited text no. 12
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.  Back to cited text no. 13
14.Gigli GL, Adorati M, Dolso P, et al. Restless legs syndrome in end-stage renal disease. Sleep Med 2004;11:309-15.  Back to cited text no. 14
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.  Back to cited text no. 15
16.Ekbom KA. Restless legs syndrome. Neurology 1960;10:868-73.  Back to cited text no. 16
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].  Back to cited text no. 17
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.  Back to cited text no. 18
19.Walker SL, Fine A, Kryger MH. Sleep com­plaints are common in dialysis unit. Am J Kidney Dis 1995;26:751-6.  Back to cited text no. 19

Correspondence Address:
Saleh Mohammad Yaser Salman
Department of Internal Medicine, Faculty of Medicine, Aleppo University, Allepo
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PMID: 21422649

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