|Year : 2016 | Volume
| Issue : 2 | Page : 326-330
|Restless legs syndrome in hemodialysis patients
Shahram Rafie1, Majid Jafari1, Mostafa Azizi1, Mohammad Bahadoram2, Shima Jafari2
1 Department of Neurology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Medical Student Research Committee; Chronic Kidney Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Click here for correspondence address and email
|Date of Web Publication||11-Mar-2016|
| Abstract|| |
Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable sensation of paresthesia in legs that subsequently causes involuntary and continuous movement of the lower limbs, especially at rest. Its prevalence in hemodialysis is more than that in the general population. Different risk factors have been suggested for RLS. We studied the prevalence and risk factors of RLS in 137 hemodialysis patients followed up at our center. The patients completed at least three months on dialysis and fulfilled four criteria for the diagnosis of RLS. We compared the patients with and without RLS, and the odds ratios (ORs) were estimated by the logistic regression models. The prevalence of RLS was 36.5% in the study patients. Among the variables, diabetes was the only predicting factor for the development of RLS. The diabetic patients may be afflicted with RLS 2.25 times more than the non-diabetics. Women developed severe RLS 5.23 times more than men. Neurodegeneration, decrease in dopamine level, higher total oxidant status, and neuropathy in diabetic patients may explain the RLS symptoms.
|How to cite this article:|
Rafie S, Jafari M, Azizi M, Bahadoram M, Jafari S. Restless legs syndrome in hemodialysis patients. Saudi J Kidney Dis Transpl 2016;27:326-30
|How to cite this URL:|
Rafie S, Jafari M, Azizi M, Bahadoram M, Jafari S. Restless legs syndrome in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Feb 22];27:326-30. Available from: http://www.sjkdt.org/text.asp?2016/27/2/326/178553
| Introduction|| |
The diagnostic symptoms of restless legs syndrome (RLS) include uncomfortable sensation of paresthesia in legs and involuntary and continuous movement of the lower limbs. The symptoms are relieved by physical activity and are aggregated while resting.  RLS causes sleep disorders and results in insomnia in 50-80% of the cases. The prevalence of RLS is 5-15% in the general population.  The prevalence in patients undergoing hemodialysis therapy ranges from 8.8-83%. , Although RLS has a high prevalence, there is controversy about the management of this syndrome in hemodialysis patients, and nearly about 20% of RLS patients leave dialysis sessions incomplete because of the symptoms of this syndrome. 
One of the important proposed mechanisms causing this syndrome is decreased release of dopamine from the a11 dopaminergic neurons located in the dorso-posterior part of hypothalamus.  The loss of the suppressive effect of dopamine on spinal cord reinforces the signals of the sensory neurons to spinal dorsal horn, and a wide range of uncomfortable sensory symptoms that affect the quality of life ensue in the lower parts of the body. 
The International RLS study group has suggested the following clinical criteria for the diagnosis of RLS: uncomfortable and irritating sensation in the legs that urges the individual to walk or move the legs, the symptoms emerge or aggravate at rest during sitting or lying down in the bed, and are relieved by moving the legs, the symptoms are aggravated in the evening or night, especially at rest, and the movement restlessness is observed as small minimal movements in the toes and calves and/or sudden twisting movements of the legs in bed. ,
RLS may be primary or secondary to different medial conditions such as iron deficiency, pregnancy, neuropathy, or end-stage renal disease.  Different factors including female gender, diabetes mellitus, low serum hemoglobin, hemodialysis vintage, and elevated levels of parathormone are suggested as the risk factors for RLS. ,
RLS has different prevalence in the different ethnicities. The prevalence and risk factors of this syndrome had not been determined in South-West of Iran.
We aimed in this study to determine the prevalence, risk factors, and severity of RLS in our hemodialysis population.
| Methods|| |
The participants of this cross-sectional study were 137 patients including 73 males and 64 females from the dialysis centers of Razi and Golestan Hospitals in Ahvaz. The study was approved by the ethics and research committee of Ahvaz University of medical science (code: 1392.236), and it was started in May and ended in July 2014. The patients ranged from 17-84 years of age. The minimum dialysis duration for the patients to participate in the study was three months. The patients underwent hemodialysis from an arterio-venous fistula regularly three times a week with 4-6 h each time. The dialysis buffer was bicarbonate and the membrane of the filters was of cellulose diacetate. The patients with low-level of consciousness, the ones unable to respond appropriately and current users of antihistamines, antidepressants, and dopamine antagonist drugs were excluded from the study.
Demographic and medical data were extracted from the patients' files. Then, the patients were evaluated for their RLS by a neurologist. The syndrome was diagnosed according to the diagnostic criteria proposed by "International RLS Study Group" (IRLSSG). The IRLSSG Severity-scale questionnaires were filled for the patients who had all the four symptoms of this syndrome. The questionnaire included 10 questions. The response to each item had a total score of 0-40. Based on this questionnaire and in terms of severity of the disease, the patients were divided into four groups of mild (0-10), moderate (11-20), severe (21- 30), and very severe (31-40) RLS. After the interview, pre-dialysis blood samples of all the patients were obtained, and their hemoglobin and blood urea nitrogen (BUN) were measured.
| Statistical Analysis|| |
Data were analyzed by SPSS software version 16.0 (SPSS Inc., Chicago, IL) and the mean values and standard deviations were determined. To determine the risk factors, demographic and laboratory factors of the patients with and without RLS were compared. A Chi-squared test was used to analyze the qualitative data, and a t-test method was used for quantitative analysis. The odds ratios (ORs) were estimated by the logistic regression models. P <0.05 was considered as statistically significant difference.
| Results|| |
The 137 study patients included 73 (53.3%) males, 64 (46.7%) females, 43 patients (32.1%) with diabetes, and 93 patients (67.9%) without diabetes. The participants' ages ranged from 17-84 years with a mean of 67 years. There were 50 (36.5%) patients diagnosed with RLS. The mean age of the RLS patients was 56.1 ± 9.80 years and that of the non-RLS patients was 1.50 ± 14.6 years. The mean BUN was 46.9 ± 13.8 mg/dL in the RLS group and 44.8 ± 16.4 mg/dL in the non-RLS group. The mean hemoglobin was 9.47 ± 1.40 g/dL in the RLS group and 9.23 ± 1.41 g/dL in the non-RLS group. The dialysis duration in the RLS group was 2.53 ± 2.16 years and 2.57 ± 2.85 years in the non-RLS group. Among the variables, diabetes was the only predicting factor for the development of RLS. The diabetic patients may be afflicted with RLS, 2.25 times more than the non-diabetic ones [Table 1] and [Table 2]. Four (8%) patients had the symptoms of the syndrome before the initiation of dialysis and only two (4%) patients had a positive family history of RLS.
|Table 1: Characteristics of study patients separated by having restless leg syndrome (RLS) or not.|
Click here to view
|Table 2: Association of restless leg syndrome and patient characteristics using logistic regression.|
Click here to view
The severity of RLS was not different among diabetic and non-diabetic patients. Women developed more severe RLS (5.23 times) more than men [Table 3]; one (1.6%) woman had mild, four (6.5%) women had moderate, nine (14.5%) women had severe, and 10 (16.1%) women had very severe RLS. Among men, no one had mild RLS, nine (13%) had moderate, eight (11.6%) had severe, and three (4.3%) had very severe RLS.
|Table 3: Association of restless leg syndrome severity and patient characteristics, using logistic regression.|
Click here to view
| Discussion|| |
The prevalence of RLS is different among dialysis centers of different countries. The prevalence of this syndrome has been reported as 18.9-30.1% in Taiwan,  26.6% in Greece,  21.5% in Brazil and Italy, , 22% in Saudi Arabia,  and 34.1% in Turkey.  In our study, the prevalence of RLS was 36.5%. The difference in the prevalence may be due to race differences of the different populations. ,
In the majority of patients, symptoms of RLS appeared after long duration of dialysis. Only 8% of the patients had the symptoms on shortterm dialysis. This indicates that RLS is not genetic and idiopathic, but secondary to hemodialysis.  The high prevalence of RLS in hemodialysis patients is proportionate to further loss of kidney function after initiation of dialysis. 
Some previous studies have reported that the prevalence of RLS increases with the advancement of age. , In our study, the syndrome was not related to age, although it was carried out in the same way as previous studies. ,, Furthermore, some prior studies have shown that RLS was more prevalent in females, ,, but we did not find this result.
In our study, hemoglobin and BUN levels and duration of hemodialysis were not risk factors of RLS, and this was comparable with the results of some large studies. 
Previous studies have indicated the relationship between diabetes and RLS; , diabetes was also a risk factor of RLS in our study. Glucose disorders and resistance to insulin with different mechanisms lead to neurodegeneration. Glucose and insulin disorders cause a decline in neurogenesis and a decrease in neuronal repair, and insulin disorders also result in dysfunction of the brain in adjusting the density of dopamine receptors and development of RLS symptoms.  In addition, studies on diabetic rats show a decrease in dopamine level in striatum and midbrain, and these two areas have an important role in RLS cycle.  A decrease in the level of dopamine in central nervous system in diabetic patients decreases the central inhibitory effects on spinal cord and leads to RLS symptoms.
Studies have shown that idiopathic RLS patients have higher total oxidant status than normal people.  On one hand, oxidative stress has been identified as a factor in uremic RLS  and diabetic patients have high levels of oxidative stress.  Hence, oxidative stress may have a role in the high prevalence of RLS in diabetic hemodialysis patients.
Many diabetic patients have neuropathy and suffer from neuropathic pain. It has been proven that drug treatment of neuropathic pain with pregabalin can decrease neuropathic pain as well as RLS symptoms.  On the other hand, neuropathy is prevalent among hemodialysis patients.  Therefore, neuropathy can be a major factor in developing RLS in hemodialysis and diabetic patients. Extensive studies on electromyography and nerve conduction in RLS patients can determine the role of this factor. In the present study, the severity of RLS was not related to any other factor except gender and symptoms of RLS. RLS was more severe in women and we did not find any clear reason for that.
In conclusion, in our study, the prevalence of RLS was 36.5%. Different prevalence rate for RLS may be due to racial differences, and it seems neurodegeneration, lower dopamine level, higher total oxidant status, and advanced diabetic neuropathy may result in the exacerbation of the RLS symptoms.
Source of Support
This study is part of thesis for Majid Jafari. Hereby, we wish to thank all our colleagues in Department of Neurology. Financial support was provided by Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (Grant No. U-92185).
Conflict of Interest
All authors declare that there is no conflict of interests.
| References|| |
Soyoral Y, Sayarlioglu H, Tuncel D, ªahin M, Dogan E, Erkoc R. Prevalence and risk factors of restless leg syndrome in a single hemodialysis unit. Turk J Med Sci 2010;40:443-6.
Lipford MC, Silber MH. Long-term use of pramipexole in the management of restless legs syndrome. Sleep Med 2012;13:1280-5.
Szentkiralyi A, Molnar MZ, Czira ME, et al. Association between restless legs syndrome and depression in patients with chronic kidney disease. J Psychosom Res 2009;67:173-80.
Tuncel D, Orhan FO, Sayarlioglu H, Isik IO, Utku U, Dinc A. Restless legs syndrome in hemodialysis patients: Association with depression and quality of life. Sleep Breath 2011; 15:311-5.
Beladi-Mousavi SS, Jafarizade M, Shayanpour S, Bahadoram M, Moosavian SM, Houshmand G. Restless Legs Syndrome: Associated Risk Factors in Hemodialysis Patients. Nephrourol Mon. 2015;7(6).
Trenkwalder C, Paulus W. Restless legs syndrome: Pathophysiology, clinical presentation and management. Nat Rev Neurol 2010;6:337-46.
Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless Legs Syndrome Diagnosis and Epidemiology Workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-19.
Allen RP, Picchietti DL, Garcia-Borreguero D, et al. International Restless Legs Syndrome Study Group. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria-history, rationale, description, and significance. Sleep Medicine 2014;15(8): 860-73.
Stefanidis I, Vainas A, Dardiotis E, et al. Restless legs syndrome in hemodialysis patients: An epidemiologic survey in Greece. Sleep Med 2013;14:1381-6.
Araujo SM, de Bruin VM, Nepomuceno LA, et al. Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities. Sleep Med 2010;11:785-90.
Gigli GL, Adorati M, Dolso P, et al. Restless legs syndrome in end-stage renal disease. Sleep Med 2004;5:309-15.
Al-Jahdali HH, Al-Qadhi WA, Khogeer HA, AlHejaili FF, Al-Ghamdi SM, Al Sayyari AA. Restless legs syndrome in patients on dialysis. Saudi J Kidney Dis Transpl 2009;20:378-85.
Yuksel S, Colbay M, Yaman M, Uslan I, Acarturk G, Karaman O. Evaluation of the diagnostic criteria of restless leg syndrome in hemodialysis patients. Eur J Gen Med 2007;4: 145-8.
Lee HB, Hening WA, Allen RP, Earley CJ, Eaton WW, Lyketsos CG. Race and restless legs syndrome symptoms in an adult community sample in east Baltimore. Sleep Med 2006;7:642-5.
Zucconi M, Ferini-Strambi L. Epidemiology and clinical findings of restless legs syndrome. Sleep Med 2004;5:293-9.
Markou N, Kanakaki M, Myrianthefs P, et al. Sleep-disordered breathing in nondialyzed patients with chronic renal failure. Lung 2006; 184:43-9.
Wesstrom J, Nilsson S, Sundstrom-Poromaa I, Ulfberg J. Restless legs syndrome among women: Prevalence, co-morbidity and possible relationship to menopause. Climacteric 2008; 11:422-8.
Hening WA, Allen RP, Chaudhuri KR, et al. Clinical significance of RLS. Mov Disord 2007;22 Suppl 18:S395-400.
Benediktsdottir B, Janson C, Lindberg E, et al. Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality of life. Sleep Med 2010;11:1043-8.
Erer S, Karli N, Zarifoglu M, Ozcakir A, Yildiz D. The prevalence and clinical features of restless legs syndrome: A door to door population study in Orhangazi, Bursa in Turkey. Neurol India 2009;57:729-33.
Kim KW, Yoon IY, Chung S, et al. Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population - Results from the Korean Longitudinal Study on Health and Aging. J Sleep Res 2010;19(1 Pt 1):87-92.
Mao S, Shen H, Huang S, Zhang A. Restless legs syndrome in dialysis patients: A meta-analysis. Sleep Med 2014;15:1532-8.
Craft S, Watson GS. Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurol 2004;3:169-78.
Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: An emerging threat to patient outcome. Nephrol Dial Transplant 2003;18:1272-80.
Sagheb MM, Dormanesh B, Fallahzadeh MK, et al. Efficacy of Vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: A randomized, doubleblind, placebo-controlled trial. Sleep Med 2012; 13:542-5.
Sommer M, Bachmann CG, Liebetanz KM, Schindehütte J, Tings T, Paulus W. Pregabalin in restless legs syndrome with and without neuropathic pain. Acta Neurol Scand 2007;115:347-50.
Krishnan AV, Phoon RK, Pussell BA, Charlesworth JA, Bostock H, Kiernan MC. Altered motor nerve excitability in end-stage kidney disease. Brain 2005;128(Pt 9):2164-74.
Department of Neurology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
[Table 1], [Table 2], [Table 3]
| Article Access Statistics|
| Viewed||2395 |
| Printed||21 |
| Emailed||1 |
| PDF Downloaded||494 |
| Comments ||[Add] |