| Abstract|| |
Insomnia and limb pain are common problems in dialysis patients. In addition, restless leg syndrome (RLS) as a specific cause of insomnia and limb pain has been reported in many studies. The purpose of this study was to estimate incidence of insomnia and RLS as a cause of insomnia in these patients. Twenty-six patients undergoing hemodialysis were investigated for insomnia, limb pain and RLS as per the defined criteria. They were evaluated for dialysis quality, dialysis duration, hemoglobin, serum phosphorous, ionized calcium, iron and ferritin levels. These variables between patients with insomnia and those with normal sleep were evaluated by independent "t" test. Without considering the etiology or pathogenesis of insomnia, we evaluated the occurrence of insomnia and limb pain in these patients, and specifically, restless leg syndrome. Insomnia and limb pain were common in dialytic patients. 46% of patients had insomnia. 91% of sleepless group had limb pain as a persistent, annoying complaint. Limb pain was not seen in groups with a normal sleep pattern. Restless leg syndrome was found in 8% of total cases (2 out of 26) and 17% among the insomnia group (2 out of 12). In spite of high incidence of insomnia among patients undergoing regular hemodialysis, role of RLS is trivial. There is a strong relationship between hemoglobin levels and duration of renal replacement therapy to insomnia occurrence.
|How to cite this article:|
Malaki M, Mortazavi FS, Moazemi S, Shoaran M. Insomnia and limb pain in hemodialysis patients: What is the share of restless leg syndrome?. Saudi J Kidney Dis Transpl 2012;23:15-20
|How to cite this URL:|
Malaki M, Mortazavi FS, Moazemi S, Shoaran M. Insomnia and limb pain in hemodialysis patients: What is the share of restless leg syndrome?. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2021 Jan 18];23:15-20. Available from: https://www.sjkdt.org/text.asp?2012/23/1/15/91289
| Introduction|| |
Insomnia is defined as a subjective sensation of short, unsatisfying sleep despite the ability to sleep.  Several variables including the definition and classification of insomnia may be responsible for the wide range seen in the prevalence of insomnia in general population, reported as between 4 and 29%. , Sabbatini et al evaluated dialysis patients having insomnia to find out whether there was any relationship between insomnia and hyperparathyroidism-induced renal osteodystrophy, which may explain the limb pain.  Restless leg syndrome (RLS) is defined as an unpleasant sensation in the lower extremities, which may be an early manifestation of chronic kidney disease (CKD) that worsens during evening with diverse pain patterns like burning, swelling sensation, constriction and tenderness of distal parts of lower extremity associated with continuous leg movements. , RLS is an important cause of sleep disturbance that may occur in 5-15% of normal population,  whereas among dialysis patients, RLS prevalence is reported to vary from 6 to 60%, ,, attributed to anemia. , Another study found that RLS was related to low serum parathyroid hormone, but not to low hemoglobin.  Others have found that RLS in dialysis patients is related to increased cardiac as well as infectious complications.  The aim of this study was to find out the prevalence of insomnia and limb pain in general and to ascertain the prevalence of RLS as a specific cause of limb pain and insomnia that may affect survival and life quality of dialysis patients. In addition to this, our aim was to find whether there was any exclusive relationship of insomnia with other variables like adequacy of dialysis as measured by urea clearance (eKt/V), anemia, phosphorous, ionized calcium, serum iron and ferritin levels.
| Patients and Methods|| |
Patients were selected from our hemodialysis center. Those who had documented end-stage kidney disease, who were on hemodialysis for at least six months and who had good mental state without history of any neurological diseases were selected.
They were being dialyzed at least 12 hours a week and their urea clearance was estimated monthly by using Daugirdas formula. ,,, The residual renal function of patients who were not anuric (urine output more than 1 mL/kg/ hour in children or an interdialysis diuresis of 250 mL or 125 mL daily for adults) was estimated by collecting urine 24 hours before dialysis. Serum Urea Nitrogen concentration (SUN) in formula 1 was done on a sample taken while the 24 hour urine collection was being done prior to dialysis. This value was found roughly equal to 90% of pre-dialysis urea sample level. Urine Urea Nitrogen concentration (UUN) was measured in the same units as of SUN and residual Kt/V was measured by formula 1: [RKt/V = UUN/ SUN × urine flow rate (mL/min)]  and was added to eKt/V. Total or TKt/V was measured by formula 2 (TKt/V weekly = 3 eKt/V dp + weekly RKt/V). 
Their hemoglobin, serum iron, ferritin and phosphorous were all measured along with urea clearance and were recorded.
Duration of each dialysis was that which was prescribed for them at the time of initiation of dialysis, based on uremic symptoms or when the estimated glomerular filtration rate (eGFR) was less than 10, estimated by Modification of Diet in Renal Disease (MDRD) formula. These patients were asked for the presence of symptoms of insomnia such as difficulty in falling asleep, frequent awakening with difficulty in falling asleep again and early morning awakening at least for three to four times per week and whether they had persisted for several weeks. ,
All patients were then asked for the presence of unpleasant persistent leg pain, paresthesia, burning or itching. They were evaluated for RLS based on the criteria proposed by International Restless Legs Study Group (IRLSSG) that can be simplified into four questions:
For the diagnosis of RLS, a positive reply was needed for all four questions. 
- Did you experience a desire to move your leg associated with unpleasant sensation like crawling, paresthesia, and pain?
- Did you sometimes notice motor restlessness?
- Do symptoms occur or worsen at rest or during inactivity, and does moving improve them?, and
- Are symptoms more pronounced in the evening or at night compared to morning?
| Results|| |
Twenty-six patients (6 males and 20 females) with a mean age ± SD (35.7 years ± 21.9), undergoing chronic dialysis for an average duration of 34.8 ± 18 months (range 9-75 months) were selected for this study. The patients were divided into two groups: those who had insomnia (group 1) and normal sleep (group 2). Twelve patients (46%) had insomnia and 11 out of 12 patients described of painful sensations that disturbed their sleep. Only in 2 out of 26 patients (7%) and 2 out of 11 (18%) who had limb pain the complaints were compatible with RLS. Along with this, we also compared laboratory findings including serum iron, ferritin, free calcium, phosphorous, creatinine, hemoglobin, eKt/V dp and duration of dialysis [Table 1].
|Table 1: Patients' characteristics in two groups of sleep pattern under hemodialysis.|
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There was no correlation between age and insomnia. The age (mean ± SD) of insomnia group was 40 years ± 21/7 (range: 7-65 years) and in those with good quality of sleep it was 33 years ± 22/5 (range: 9-70 years). These were statistically not significant (P = 0.13).
Quality of dialysis was defined on the basis of Kt/V; as of low quality when it was equal or below 1.2 and high quality when above 1.2. Kt/V (mean ± SD) in insomnia group was 1.29 ± 0.38 and in normal group the value was 1.57 ± 0.5 (P =0.13). Insomnia was found in 44% in low-quality dialysis group, whereas it was found in 47% of those with Kt/V above 1.2 (P >0.05).
Serum iron and ferritin were measured and compared between the two groups, i.e. with insomnia and without insomnia. Serum ferritin in insomnia group was (mean ± SD) 601 ± 272 μg/L and in those without insomnia it was 426 ± 266 μg/L and there was no statistically significant difference between these two groups.
Serum iron measured in insomnia group was (mean ± SD) 185.8 ± 219 μg/dL and in normal sleep pattern it was (mean ± SD) 89.5 ± 48 μg/dL. There was no significant relation between serum iron and sleep pattern in our patients (P >0.05) [Table 1].
Serum phosphorous and free calcium levels in groups with insomnia and without insomnia were also found to be not significantly different between the two groups [Table 1].
Another feature to be evaluated was their anemia. Hemoglobin was measured as pre-dialysis and the value (mean ± SD) in insomnia group was 10.0 ±1.6 g/dL and in the normal group was 11.6 ± 0.8 g/dL. The difference between hemoglobin values in the insomnia group and those with normal sleep pattern was statistically significant (P= 0.004).
The period of dialysis from the time of initiation of dialysis for end-stage renal disease (ESRD) to the time of this study was evaluated between two groups. Insomnia group had been on hemodialysis for 42 ± 19 months (mean ± SD) and in the normal group the period was 28 ± 16 months (mean ± SD). There was significant correlation with the period on dialysis therapy and insomnia (P = 0.04).
| Discussion|| |
This study was performed on 26 patients undergoing dialysis regularly to find out their sleep disorders associated with leg pain and to estimate the frequency of RLS as well as to correlate the effects of other variables on insomnia in dialysis patients.
Sleep disorders is a common problem among dialysis patients. , It is estimated that it affects 69% of patients and RLS contributes to 18% of insomnia cases. About 3.6% patients use hypnotic drugs for their insomnia.  Other studies report a different picture about RLS, with an incidence between 6 and 60% in this group of patients. ,,
In our study based on four standard questions of IRLSSG, unpleasant sensations of lower limb that cause sleep disturbance were common in as much as 46%, but all the criteria of RLS were met only in 7.5% of all patients and accounted for only 17% of patients with insomnia. 7.5% incidence of RLS found in our study was not significantly different from 3- 15% of RLS reported in the general population.  Insomnia and limb pain are the common complaints of patients, but the role of RLS is trivial.
Although the character of unpleasant senses differed in patients, the most common complaint was limb pain that may be associated with burning sensation and/or itching or solely pain. Only one patient had insomnia without limb discomfort. Thus, this study shows strong association between insomnia and limb pain in these patients.
There was no relation between insomnia and age, sex or dialysis quality measured by eKt/V. They were on dialysis therapy for 9-75 months. Ten out of 12 could remember the onset of insomnia and six out of ten had insomnia only after initiation of dialysis therapy.
In a multivariate analysis, factors that were independently associated with poor sleep quality were male gender, phosphate level and coronary artery disease.  But in our study, serum phosphorous levels were not different between those who were affected with insomnia and those with normal sleep. Another interesting fact found in our study was that the insomnia in males was lower than in females (33 vs. 50%). Sabbatini et al found that there were no differences in Hb concentrations of patients under dialysis with or without insomnia (4).
Delano et al  have reported an improvement in insomnia in hemodialysis patients by using erythropoietin (EPO) and this was confirmed by Benz et al.  A rise in hematocrit (Hct) value from 32.3 to 42.3 induces a significant reduction in the occurrence of periodic limb movements in sleep.
In our study, anemia measured by Hb was significantly different between patients with insomnia and those with normal sleeping pattern. Regardless of having RLS or not, the average level of Hb was 10 g/dL in patients with insomnia and 11.6 g/dL in patients without insomnia. Serum iron and ferritin levels did not have any role in predicting the risk of insomnia in these patients.
Some believe that higher urea and creatinine levels are an evidence of poor dialysis efficacy may contribute to insomnia incidence. , In our study, creatinine level before dialysis session and eKt/V as a standard tool for dialysis efficacy was not different between the two groups, i.e. those with insomnia and those without insomnia.
Chronic dialytic therapy may cause insomnia by mechanisms such as increased incidence of renal osteodystrophy that is associated with limb pain and/or pruritis. These two symptoms were seen in 24% of patients. 
In our study, longer period of dialytic therapy was associated with increased occurrence of insomnia (P = 0.04), although this may be partly related to increased incidence of renal osteodystrophy which is associated with bone pain and pruritis as noted by Sabbatini et al in their study.  Insomnia due to limb pain and pruritis occurred in 26% of our patients, which is similar to what was reported by Sabbatini et al.  This shows that control or prevention of renal osteodystrophy may be a way to decrease an important cause of insomnia in dialysis patients. However, this needs to be evaluated by further studies with larger number of patients.
Insomnia is a common problem in chronic dialytic therapy that has relation to anemia and duration of dialysis as renal replacement therapy. Limb pain was seen in 11 out of 12 cases of insomnia, but RLS was found only in a small proportion of patients with limb pain and insomnia (2 out of 11 cases). Insomnia was not related to age, serum iron or ferritin levels, serum creatinine or dialysis adequacy. Serum phosphorous or ionized calcium levels were found to have no role in insomnia, but renal osteodystrophy is an important cause of insomnia due to its limb pain and pruritis. Although we had only a small sample in this study, this is one of the first that tried to associate dialysis quality and insomnia. We feel that in future some of the management standards should be modified for insomnia patients on dialysis for improving their quality of life.
| Acknowledgment|| |
We dedicate this study to the soul of our staff, Mrs. H. Jafarnejad, who passed away during this study. God bless her.
| References|| |
|1.||Meyer TJ. Evaluation and management of insomnia. Hosp Pract 1998;33:75-8. |
|2.||Leger D, Guillerminault C, Dreyfus JP, Delahaye C, Paillard M. Prevalence of insomnia in a survey of 12778 adults in France. J Sleep Res 2000;9:35-42. |
|3.||Chesson A Jr, hartse K, Anderson WM, et al. Practice parameters for evaluation of chronic insomnia. An American Academy of sleep medicine. Sleep 2000;23:237-41. |
|4.||Sabbatini M, Minale B, Crispo A, et al.. Insomnia in maintenance haemodialysis patients. Nephrol Dial Transplant 2002;17:852-6. |
|5.||Fernandez JP, McGinn JT, Hoffman RS. Cerebral edema from blood-brain glucose differences complicating peritoneal dialysis' second membrane syndrome. N Y State J Med 1968;68:677. |
|6.||Schneck SA. Neuropathological features of human organ transplantation 1. J Neuropathol Exp Neurol 1965;24:415. |
|7.||Martin CM. The mysteries of restless leg syndrome. Consult Pharm 2007;22:907-24. |
|8.||Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis 1995;26:751. |
|9.||Thorp ML. Restless legs syndrome. Int J Artif Organs 2001;24:755. |
|10.||Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis 2004;43:43. |
|11.||Harris DC, Chapman JR, Stewart KH, et al. Low dose erythropoietin in maintenance haemo-dialysis: Improvement in quality of life and reduction in true cost of haemodialysis. Aust N Z J Med 1991;21:693. |
|12.||Sloand JA, Shelly MA, Feigin A, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004;43:663. |
|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;31:132. |
|14.||Gigli GL, Adorati M, Dolso P, et al. Restless legs syndrome in end-stage renal disease. Sleep Med 2004;5:309-15. |
|15.||NKF-DOQI. Clinical practice guidelines for hemodialysis adequacy. Am J Kidney Dis 1997;30(Suppl 2):15-63. |
|16.||Daugirdas JT. Second generation logarithmic estimates of single pool variable volume Kt/V: An analysis of error. J Am Soc Nephrol 1993;4:1205-13. |
|17.||Daugirdas JT. Estimation of equilibrated Kt/V using the unequilebrated post dialysis BUN. Semin Dial 1995;8:283-4. |
|18.||Daugirdas JT, Schneditz D. Overestimation of hemodialysis dose depends on dialysis efficiency by regional blood flow but not by conventional two pool urea kinetic analysis .ASAIO J 1995;41:719-24. |
|19.||Daugirdas JT, Van Stone JC. In: "Handbook of Dialysis". (Daugirdas JT) 3nd ed. Williams & Wilkins , USA 2001;15-45. |
|20.||Teschan PE. Role of Kt/V urea in dialysis. Semin Dial 1990;3:77-8. |
|21.||Merlino G, Piani A, Dolso P, et al. Sleep disorder in patients with end stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant 2006;21:184-90. |
|22.||Thorpy MJ. New paradigms in the treatment of restless legs syndrome. Neurology 2005;64(12 Suppl 3):28-33. |
|23.||Holley JL, Nespor S, Rault R. A comparison of reported sleep disorders in patients on chronic hemodialysis and continuous peritoneal dialysis. Am J Kidney Dis 1992;19:156-61. |
|24.||Walker S, Fine A, Kryger MH. sleep complaints are common in dialysis unit. Am J Kidney Dis 1995;26:751-6. |
|25.||Unruh ML, Hartunian MG, Chapman MM. Sleep quality and clinical correlates in patients on maintenance dialysis. Clin Nephrol 2003; 59:280-8. |
|26.||Delano BG. Improvement in quality of life following treatment with r-Hu-Epo in anemic hemodialyis patients. Am J Kidney Dis 1989; 14:14-8. |
|27.||Benz RL, Pressman MR, Hovick ET, Peterson DD. A preliminary study of the effects of correcrection of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders and day time sleepiness in hemodialysis patients (The SLEEPO Study). Am J Kidney Dis 1999;34:1089-95. |
|28.||De Vecchi A, Finnazi S, Padalino R, et al. Sleep disorders in peritoneal and hemodialysis patients as assessed by a self-administered questionnaire. Int J Artif Organs 2000;23:237-42. |
Assistant Professor of Pediatric Nephrology, Tabriz Medical University, Post Code 5136735886, Tabriz