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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 3  |  Page : 625-650
Restless leg syndrome in hemodialysis patients: A disorder that should be noticed

1 Social Determinants of Health Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
2 Occupational Sleep Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 Metabolic Disease Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
4 Division of Nephrology, Qazvin University of Medical Sciences, Qazvin, Iran
5 Qazvin University of Medical Sciences, Qazvin, Iran

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Date of Web Publication20-May-2015


Restless leg syndrome (RLS) is a distressing sleep disorder that is commonly experienced by patients undergoing maintenance hemodialysis. The aim of this study was to assess the prevalence of RLS and its related factors among hemodialysis patients. This was an analytical cross-sectional study that was performed on hemodialysis patients of the Bu"Ali Hospital of Qazvin during 2009 and 2010. One hundred and twelve patients were selected by the census sampling method as the study sample. Data collection was performed using the Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index (PSQI), Berlin, Epworth Sleepiness Scale (ESS) and International Restless Leg Syndrome Study Group criteria (IRRLS) questionnaires. Student's ttest and chi-square test were applied to analyze the collected data. RLS complaints were very common among patients on long-term dialysis therapy and were reported in about 42.9% of the patients. Patients with RLS had higher daytime sleepiness, insomnia complaints and poorer sleep quality. Percentage of patients in the high-risk group was higher in the RLS group. RLS symptoms appear to be correlated with age (P = 0.012) and use of sedative drugs (P = 0.035). RLS is common in dialysis patients and is associated with a higher prevalence of other sleep disturbances. Therefore, the effective assessment and management of this sleep disturbance has the potential to significantly enhance patient outcomes.

How to cite this article:
Yazdi Z, Sadeghniiat-Haghighi K, Kazemifar AM, Kordi A, Naghipour S. Restless leg syndrome in hemodialysis patients: A disorder that should be noticed. Saudi J Kidney Dis Transpl 2015;26:625-50

How to cite this URL:
Yazdi Z, Sadeghniiat-Haghighi K, Kazemifar AM, Kordi A, Naghipour S. Restless leg syndrome in hemodialysis patients: A disorder that should be noticed. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Jun 25];26:625-50. Available from: https://www.sjkdt.org/text.asp?2015/26/3/625/157431

   Introduction Top

Patients with end-stage renal diseases commonly suffer from sleep disorders even before the initiation of renal replacement therapy, i.e. hemodialysis. [1],[2] It has been claimed that 50-80% of the patients experience a number of complaints related to sleep. The scope of sleep disorders in the patients ranges from insomnia, day time sleepiness and sleep apnea to restless leg syndrome (RLS). [3],[4]

RLS is quite common among patients who are on long-term hemodialysis. Its prevalence has been reported to range from 6% to 80% in various studies. [5],[6] RLS may adversely influence the quality of life in such patients. [7] RLS is a relatively unpleasant disorder that forces the patient to an irresistible urge to move the legs. It generally begins before start of sleep and may hamper initiation of sleep; in this way, it results in a sleep disorder. [8]

RLS may be idiopathic in origin or secondary to other diseases such as pregnancy, rheumatoid arthritis and uremia. It is seen in 5-15% of the general population. [9] The pathophysiology of RLS remains to be determined. However, it has been suggested that patients with musculoskeletal malformations, anemia, vitamin or iron deficiency and disturbance in the central nervous system (CNS) or peripheral nervous system (PNS) functions are also prone to RLS. Furthermore, peripheral neuropathy resulting from uremia, diabetes, musculoskeletal malformations and secondary hyperparathyroidism may increase the chance of RLS in dialysis patients.

In another study, the prevalence of RLS among dialysis patients was reported to be 48%, and it was also reported that RLS holds up initiation of sleep in the patients; in addition, 42% of them have frequent night awakenings due to RLS. [10] In another study conducted on 9110 patients with end-stage renal disease (ESRD), it has been shown that there are strong associations between severity of RLS and some complaints of the patients that are related to sleep, such as night awakening, prolonged sleep-onset latency, higher levels of inadequate sleep and use of sedative-hypnotic drugs. [11] It is also reported that RLS is more prevalent among female dialysis patients compared with males. [12] Nevertheless, there is insufficient and conflicting data about the relationship between RLS and some metabolic markers, particularly serum blood urea nitrogen (BUN) and creatinine. Also, no correlation between RLS and anemia has been found in some studies performed on dialysis patients. [13]

The present study was conducted to assess the factors related to the occurrence of RLS in dialysis patients.

   Materials and Methods Top

One hundred and twelve patients who were referred to the hemodialysis ward of Buali hospital, a university teaching hospital in Qazvin city, Iran for their scheduled hemodialysis were included in the study if they were willing and gave signed informed consent for participation in the study. Their demographic data, namely their age, gender, duration of end-stage renal disease (ESRD), time and duration of scheduled hemodialysis, history of any related disease and drug history, were recorded using a checklist. The variables that show effectiveness of hemodialysis included urea reduction ration (URR), Kt/V index (for evaluation of dialysis efficacy) and laboratory data such as hemoglobin (Hb), white blood cell (WBC) count, pre-dialysis and post-dialysis blood urea nitrogen (BUN) and serum concentration of albumin, creatinine, alkaline phosphates, iron, ferritin, calcium, phosphorus, cholesterol, triglyceride and fasting blood sugar (FBS) were also recorded.

The Insomnia Severity Index, Epworth Sleepiness Scale and Berlin's questionnaire were used for evaluating patients as regards insomnia, daily sleepiness and sleep apnea, respectively. Also, the IRLSSG questionnaire was used for assessment of presence and severity of RLS in the patients. It comprises four questions. If any patient replied "yes" to all four, it was assumed that he/she had RLS; then, he/she was requested to reply to a further 10 questions to estimate the severity of the disease.

The collected data were analyzed using SPSS software, version 16.0.

   Results Top

One hundred and twelve patients participated in the study. Their mean age was 52 years. Seventy-two (64.3%) were male. Also, 93 (83%) were married. Causes of ESRD were uncontrolled hypertension (in 29.5%), diabetes mellitus (in 19.6%), concomitant hypertension and diabetes mellitus (in 18.8%), glomerulonephritis (in 10.7%) and obstructive nephropathy (in 8.9%).

Forty-eight patients (42.9%) had RLS according to the IRLSSG questionnaire. Frequency distribution of answers of the patients to each question of the questionnaire is demonstrated in [Table 1]. Details of demographic data, dialysis variables, laboratory data and drug history of the patients with or without RLS were matched up in [Table 2], [Table 3], [Table 4] and [Table 5]. As can be seen, difference between the groups is statistically significant in their age and history of use of sedative-hypnotic drugs.
Table 1: Frequency distribution of answers of the studied patients to each question of the IRLSSG questionnaire.

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Table 2: General characteristic of the studied patients with and without RLS.

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Table 3: Comparison of dialysis variables in the studied patients with and without RLS.

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Table 4: Comparison of lab data in the studied patients with and without RLS.

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Table 5: Drug history of the studied patients with and without RLS.

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[Table 6] displays the results of assessment of the patients about sleep problems, divided as patients with or without RLS.
Table 6: Prevalence of sleep problems in patients with and without RLS.

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   Discussion Top

Chronic renal failure is now being increasingly recognized as a common disease. It is postulated that 2-3% of the world population suffers from the disease; most of them need continuous hemodialysis. About 90,000 patients are on once a week hemodialysis in Iran. Their special necessities and concerns should be taken into account. Patients with ESRD who accept hemodialysis may prolong their lives, but they suffer simultaneously from other disease syndromes and considerable distress. In the time-consuming process of hemodialysis, patients often develop various physical and psychological symptoms, which include sleep disturbances. [14]

The present study confirmed that RLS is prevalent among dialysis patients. It was seen in 42.9% of the patients. Moreover, 47.3% of them experience day time sleepiness and poor quality of sleep. Insomnia and day time sleepiness were more prevalent in patients with RLS.

The prevalence of RLS in the general population is estimated to about 12%. Its prevalence was higher in dialysis patients in our study. Various studies have reported that RLS is seen in 6-80% of dialysis patients. [5],[6] Merlino has found RLS in 18.4% of 883 patients with ESRD and maintenance hemodialysis. [15] Inconsistency in the tool used for diagnosis of the disease, inclusion criteria and ethnic variations may explain this wide discrepancy. Nonetheless, detection rates of this common disorder are still low. Therefore, safe, efficacious prevention and treatment strategies remain elusive, particularly for older adults with chronic disease. [16] Our reported prevalence is approximately at the middle of the reported range and was comparable to the study of Bastos. [17]

Kutner believes that RLS is more frequent in European hemodialysis patients compared with African patients. He also reported that the prevalence is 48% in Americans with African origin, while it is 68% in American whites. [18] The prevalence of RLS in dialysis patients has been reported to be 15% in India, 12.2% in Japan and 62% in China. [4],[5],[6]

It has been suggested that the severity of RLS is unrelated to age, gender, body weight, number of years on dialysis or median, ulnar and sural nerve amplitudes. [19] The syndrome was seen more frequently in males in the current study, a finding that is comparable to the study of Takaki. [5]

Currently, the primary underlying causes of RLS are thought to be genetic predisposition, dopaminergic dysfunction and deficiencies in iron metabolism, other factors that may be interrelated. [16] In ESRD, potential risk factors include anemia, iron deficiency, dialysis vintage, calcium/phosphate imbalance and PNS and CNS abnormalities. [20] Although normalization of hematocrit with recombinant erythropoietin has resulted in a significant reduction in periodic limb movements in a sample of dialysis patients, no specific relationship between RLS symptoms and anemia has been detected. [19] No association between RLS and serum iron, ferritin, hemoglobin (and/or anemia), serum calcium and alkaline phosphatase were found in the present study. Other related studies have reported conflicting results. Some authors have suggested that RLS has connections with Hb level, serum iron or ferritin in the general population. They suppose that iron therapy may improve symptoms of RLS. [13],[14],[15],[16] This relationship did not corroborate in the current study. On the other hand, the studied patients had been treated with iron and blood transfusion. Their mean serum ferritin concentration was 680 μg/L. This may partially explain the results. It is plausible that iron influences dopamine metabolism in the CNS, a neuro-transmitter involved in the pathogenesis of RLS.

Huiqi has found no association between RLS and serum calcium and alkaline phosphatase levels. [21] The present study has also confirmed that there is no statistically significant differrence in the serum calcium, phosphorus and alkaline phosphatase levels in hemodialysis patients with and without RLS.

There is no universally established standard way for the evaluation of efficiency of hemodialysis in the patients. However, KT/V is accepted as a guide for judgment of dialysis efficacy. It is calculated from division of urea clearance on total body urea, which is expressed as volume of distribution of urea per unit of time. 1.2 is considered acceptable for KT/V. The KT/Vs of patients with and without RLS were not statistically different in the present study and are comparable to similar studies. Furthermore, there was no association between duration of hemodialysis and RLS in the current study.

If the patients are categorized according to their time on hemodialysis, i.e. morning or afternoon, 33% of the patients were in the morning and 67% were in the afternoon. However, there was no difference in prevalence of RLS between groups. A similar finding is reported by Bastos. [17] The relationship between use of sedative-hypnotic drugs and RLS has not been reported in related studies. We feel that the association should be evaluated more thoroughly in future studies.

The symptoms of RLS are often insidious and potentially misdiagnosed. Patient caregivers should routinely question their patients about sleep patterns. Care should be given to avoid sedatives for complaints of insomnia in this patient population. [22] Current recommendations suggest dopaminergic therapy (levodopa or dopamine receptor agonists: Pramipexol, ropinirole, pergolide or cabergoline) as the firstline treatment for RLS. This group of medications is effective in reducing RLS symptoms in the general population, but limited information is available on the effect of these drugs in patients with renal failure. [23]

In the present study, patients with RLS more frequently complained of symptoms such as frequent night awakening, early morning awakening, daily sleepiness, sleep apnea and night terrors compared with patients lacking RLS. Results of the present study verified that patients on long-term hemodialysis may experience sleep disorders, particularly RLS. The patients must be evaluated for the disorder during routine follow-ups. Appropriate treatment should be started for them as required.

Conflict of interest: None.

   References Top

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Takaki J, Nishi T, Nangaku M, et al. Clinical and psychological aspects of restless leg syndrome in uremic patients on hemodialysis. Am J Kidney Dis 2003;4:833-9.  Back to cited text no. 5
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Parker KP, Kutner NG, Bliwise DL, Bailey JL, Rye DB. Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis. Health Qual Life Outcomes 2003; 1:68.  Back to cited text no. 7
Perl J, Unruh ML, Chan CT. Sleep disorders in end-stage renal disease: Markers of inadequate dialysis? Kidney Int 2006;70:1687-93.  Back to cited text no. 8
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Araujo SM, Bruin VM, Nepomuceno LA, Maximo ML, Daher EF, Bruin PF. Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities. Sleep Med 2010;11:785-90.  Back to cited text no. 12
Spencer BR, Kleinman S, Wright DJ, et al. Restless legs syndrome, pica, and iron status in blood donors. Transfusion 2013;53(8):1645-52.  Back to cited text no. 13
Yu IC, Huang JY, Tsai UF. Symptom cluster among hemodialysis patients in Taiwan. Appl Nurs Res 2012;25:190-6.  Back to cited text no. 14
Merlino G, Piani A, Dolso P, et al. Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant 2006;21:184-90.  Back to cited text no. 15
Innes KE, Selfe TK, Agarwal P. Restless legs syndrome and conditions associated with metabolic dysregulation, sympathoadrenal dysfunction, and cardiovascular disease risk: A systematic review. Sleep Med Rev 2012;16: 309-39.  Back to cited text no. 16
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Kutner NG, Zhang R, Huang Y, Bliwise DL. Racial differences in restless legs symptoms and serum ferritin in an incident dialysis patient cohort. Int Urol Nephrol 2012;44:1825-31.  Back to cited text no. 18
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Molnar MZ, Novak M, Mucsi I. Management of Restless Legs Syndrome in Patients on Dialysis. Drugs 2006;66:607-62.  Back to cited text no. 23

Correspondence Address:
Dr. Amir Mohammad Kazemifar
Metabolic Disease Research Center, Qazvin University of Medical Sciences, Qazvin
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DOI: 10.4103/1319-2442.157431

PMID: 26022045

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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