Restless Legs Syndrome in Patients on Hemodialysis: Symptom Severity and Risk Factors

Transcription

1 ORIGINAL ARTICLE J Clin Neuol 2008;4: Pint ISSN / On-line ISSN /jcn Restless Legs Syndome in Patients on Hemodialysis: Symtom Seveity and Risk Factos Jeong-Min Kim, MD a ; Hyung-Min Kwon, MD a ; Chun Soo Lim, MD b ; Yon Su Kim, MD c ; Seo-Jin Lee, MD d ; Hyunwoo Nam, MD, PhD a Deatments of a Neuology and b Intenal Medicine, Seoul Metoolitan Boamae Hosital, Seoul, Koea Deatment of c Intenal Medicine, College of Medicine, Seoul National Univesity, Seoul, Koea d Lee Seo-Jin Nehology Clinic, Seoul, Koea Received July 4, 2008 Revised Setembe 1, 2008 Acceted Setembe 1, 2008 Coesondence Hyunwoo Nam, MD, PhD Deatment of Neuology, Seoul Metoolitan Boamae Hosital, 425 Sindaebang-dong, Dongjak-gu, Seoul , Koea Tel Fax hwnam@bm.co.k Backgound and PuoseᄏRestless legs syndome (RLS) is a slee disode that fequently occus in dialysis atients, which distubs the slee and educes the quality of life. The aim of this study was to detemine the isk factos fo RLS in dialysis atients. MethodsᄏPatients who visited any of fou outatient dialysis clinics between Setembe 2005 and May 2006 wee included in this study. The diagnosis of RLS and the seveity assessment wee made using the citeia descibed by the Intenational Restless Legs Syndome Study Gou. We collected basic demogahic data, clinical infomation, and laboatoy findings, and then analyzed thei association with vaious asects of RLS using univaiate and multivaiate analyses. ResultsᄏRLS was esent in 46 (28.0%) of 164 dialysis atients. We found no significant isk facto fo inducing RLS. The edialysis seum blood uea nitogen (BUN) level in the dialysis atients with RLS was significantly coelated with RLS symtom seveity. ConclusionsᄏPedialysis BUN is elated to RLS symtom seveity. Futhe studies on the undelying mechanism ae needed. J Clin Neuol 2008;4: Key Wodsᄏestless legs syndome, hemodialysis, blood uea nitogen. Intoduction Restless legs syndome (RLS) is one of the most commonly encounteed slee disodes, and it is diagnosed when the following fou essential citeia ae met: 1) the uge to move the legs, usually with unleasant sensations; 2) the aeaance of symtoms duing inactivity o est; 3) elief with movement; and 4) wosening of symtoms in the evening o at night. 1 Thee have been significant ecent advances in knowledge of the etiology, athohysiology, isk factos, and teatment of RLS. The most fequently eoted causes of seconday RLS ae ion deficiency, neuological lesion on a eiheal neve o the sinal cod, uemia, and medications, which ae fequent medical oblems among atients with chonic enal disease. 2 Slee disodes ae common among atients undegoing dialysis fo end-stage enal disease. 3 Patients undegoing egula dialysis fequently comlain of insomnia, RLS, sleedisodeed beathing, and excessive daytime sleeiness. 3 The evalence of RLS is highe in dialysis oulations than in the geneal oulation, but thee is a wide vaiation even afte alying unified diagnostic citeia. 2,4,5 It is suggested that acial diffeences in RLS suscetibility, envionmental factos such as geogahic location, and methodological limitations including small study samles and inconsistent inteetation of diagnostic citeia could esult in this wide vaiation of the evalence. 6,7 Many authos have oosed isk factos fo RLS, but many esults of evious studies have been inconsistent. Being female, a longe duation of dialysis, ion deficiency, and the use of medications such as ticyclic antideessant o doaminegic antagonist have been consideed isk factos fo RLS among dialysis atients. 2 It is imotant to be awae of the evalence and isk factos of RLS because the esence of RLS might indicate incoect dialysis teatment and educe the quality of life in dialysis atients The esent study aimed to elucidate the eval- Coyight c 2008 Koean Neuological Association 153

2 RLS in Hemodialysis ence of RLS in atients undegoing hemodialysis in Koea and to disclose the undelying causative factos. Methods Patients who visited any of fou outatient dialysis clinics in Seoul, Koea between Setembe 2005 and May 2006 wee included in this study. The atients had to have eceived egula hemodialysis fo at least 3 months. Patients who efused to aticiate in the study o who wee unable to communicate wee excluded. A total of 164 out of 321 atients who wee eceiving egula dialysis teatment wee included in this study. Demogahic and clinical infomation was obtained by eviewing atient ecods. The basic data collected elated to the age, gende, duation of dialysis theay, enaldisease histoy, comobid-disease histoy, body mass index (BMI), and weight. The following laboatoy data wee also obtained: edialysis blood uea nitogen (BUN), ceatinine, hemoglobin, seum ion, feitin, total ion-binding caacity (TIBC), hoshate, total calcium, aathyoid homone (PTH), total biliubin, alanine aminotansfease (ALT), vitamin B 12, and folate. Infomation was also obtained on the atients cuent medications. One of the investigatos (J.M.K.) efomed face-to-face inteviews based on the questionnaie duing the dialysis sessions and, if necessay, examined atients to exclude othe diseases mimicking RLS. The questionnaie comised two ages. The fist age included the Koean vesion of the Ewoth slee scale (ESS) and fou diagnostic citeia oosed by the Intenational RLS Study Gou (IRLS-SG). 1 An ESS scoe geate than nine was consideed abnomal. Only atients who fulfilled the fou citeia fo RLS wee asked to comlete the second age of the questionnaie. The second age contained the 10-question IRLSSG Rating Scale, which was used to assess symtom seveity. 11 Continuous data ae esented hee as mean±standad deviation (SD) values. Univaiate analysis was used to comae data between atients with and without RLS. A multivaiate logistic model was ceated with RLS as the deendent vaiable. We alied Peason s coelation analysis between multile vaiables and scoes on the IRLSSG Rating Scale in the atients with RLS. <0.05 was consideed statistically significant. Statistical analysis was caied out using SPSS 12.0 K softwae. Results Foty-six (28.0%) of the 164 dialysis atients fulfilled the diagnostic citeia of RLS. The age of the study atients was 62.2±12.7 yeas. The etiology of enal disease included diabetic nehoathy in 84 atients, hyetensive nehoathy in 27 atients, glomeulonehitis in 21 atients, and miscellaneous conditions (e.g., autosomal dominant olycystic kidney disease, dug-induced nehitis, and aaoteinemia) in 18 atients. The etiology was inconclusive in 14 atients. Eythooietin was escibed in 151 (92.1%) atients, oal o aenteal ion sulements wee escibed in 152 atients (92.7%), and vitamin B 12 was escibed in 156 atients (95.1%). None of the atients wee teated with a doa agonist. The basic demogahic data of the atients ae esented in Table 1. Comaing the clinical chaacteistics of atients with and without RLS by univaiate analysis evealed that none of the vaiables was associated with the esence of RLS (Table 2). Daytime sleeiness as measued by the ESS did not diffe between atients in the RLS and non-rls gous (=0.841). We conducted multivaiate logistic egession analysis using vaiables fo which the obability was less than 0.20; that is, age, hemoglobin, ion, and ALT (Table 3). None of the vaiables diffeed significantly between the RLS and non-rls gous, but RLS atients tended to be younge (=0.053). Pedialysis BUN level and symtom seveity as measued by the IRLSSG Rating Scale wee coelated in the RLS gou (=0.05, =0.363), as indicated in Table 4 and Fig. 1. Table 1. Baseline chaacteistics of atients enolled fom fou dialysis clinics Total numbe of atients 164 Age (yeas) 62.2±12.7 Scoe on ESS 5.20±4.83 Duation of dialysis (yeas) 5.11±4.83 Height (cm) 162±8.5 Weight (kg) 60.3±10.7 BMI (kg/m 2 ) 22.5±3.8 Numbe of female atients 072 Renal-disease etiology (numbe of atients) Diabetes 84 (51.2%) Hyetension 27 (16.5%) Glomeulonehitis 21 (12.8%) Othes 18 (11.0%) Unknown 14 (8.5%)0 Comobid diseases (numbe of atients) Diabetes 124 Hyetension 109 Heatitis 012 Numbe of atients with RLS 046 RLS seveity on IRLSSG Rating Scale Mild (1-10) 18 (39.1%) Modeate (11-20) 21 (45.7%) Sevee (21-30) 07 (15.2%) ESS: Ewoth slee scale, BMI: body mass index, RLS: estless legs syndome, IRLSSG: Intenational Restless Legs Syndome Study Gou. 154 J Clin Neuol 2008;4:

3 Kim JM et al. Table 2. Summay of univaiate analysis esults Patients with RLS Patients without RLS Female atients Diabetes Heatitis ESS ± ± Daytime sleeiness* Age (yeas) ± ± Duation of dialysis ± ± (yeas) Body weight (kg) ± ± BMI (kg/m 2 ) ± ± BUN (mg/dl) ± ± Uea eduction atio (%) ± ± Ceatinine (mg/dl) ± ± Phoshate (mmol/l) ± ± Hb (g/l) ± ± Ion (μg/dl) ± ± Feitin (mg/l) ± ± TIBC (μg/dl) ± ± PTH (g/ml) ± ± Vitamin B12 (g/ml) ± ± Folate (ng/ml) ± ± Total biliubin (mg/dl) ± ± ALT (IU/L) ± ± *Patients with an ESS scoe geate than 9 wee consideed to have daytime sleeiness. RLS: estless legs syndome, ESS: Ewoth slee scale, BMI: body mass index, BUN: blood uea nitogen, Hb: hemoglobin, TIBC: total ion-binding caacity, PTH: aathyoid homone, ALT: alanine aminotansfease. Discussion This study evealed that the fequency of RLS among dialysis atients in Koea is 28.0%, which is makedly highe than the evalence of RLS in the geneal Koean oulation (12.1%). 12 The diagnosis of RLS in this study was based on Table 3. Results of multivaiate analysis of isk factos fo RLS Odds atio 95% Confidence atio Age Hb Ion ALT RLS: estless legs syndome, Hb: hemoglobin, ALT: alanine aminotansfease. IRLSSG Rating Scale Pedialysis BUN level (mg/dl) Fig. 1. The edialysis blood uea nitogen (BUN) level was significantly coelated with scoes on the IRLSSG (Intenational Restless Legs Syndome Study Gou) Rating Scale. Table 4. Results of eason s coelation analysis ESS IRLSSG ating scale Age Dialysis duation BMI Hb Ion Feitin ESS IRLSSG ating scale Age Dialysis duation BMI Hb Ion Feitin BUN * * * BUN * *<0.05. ESS: Ewoth slee scale, IRLSSG: Intenational Restless Legs Syndome Study Gou, BMI: body mass index, Hb: hemoglobin, BUN: blood uea nitogen

4 RLS in Hemodialysis the fou stict citeia oosed by the IRLSSG, and the atients wee examined by an exeienced neuologist in face-toface inteviews, which made the diagnoses highly eliable. The evalence of RLS in ou Koean oulation was highe than that eoted fo oulations in Jaan (12.2%) and India (6.6%), lowe than that eoted fo China (62%), 4,5,13 and simila to that eoted fo Chile (25.9%) and Italy (21.5%). 14,15 This wide vaiation suggests diffeent suscetibilities to RLS o methodological diffeences in study oulations. 2,6,7 Many studies have ecently been conducted in dialysis clinics to claify the isk factos fo RLS, but the esults have vaied widely. We found no significant association between RLS and any of the following factos: age, gende, duation of dialysis, comobid diseases, BMI, and laboatoy data including hemoglobin, BUN, ceatinine, ion, feitin, TIBC, PTH, folate, hoshate, ALT, and total biliubin. One of the inteesting esults of this study is that the edialysis BUN level was significantly coelated with symtom seveity in the RLS gou, although the edialysis BUN level did not diffe between the RLS and non-rls gous. The edialysis BUN level is not a ecommended indicato of dialysis efficiency o disease seveity because it is easily influenced by otein intake, body volume, and enegy metabolism. 16 Ou esults suggest that factos othe than dialysis adequacy-such as dietay otein intake, ecent infection, o body volume-ae elated to wosening of RLS. These factos might not lay a majo ole in RLS develoment, but they could aggavate RLS symtoms once the syndome aeas. Detailed clinical data including body weight change, medication ofile, and diet might hel to disclose the undelying mechanism. Iondeficiency anemia is a well-known isk facto fo RLS, and the level of seum feitin is known to be coelated with RLS seveity in some RLS atients, suggesting a close elationshi between ion metabolism and the athohysiology of RLS. 2 Howeve, this elationshi is less clea in RLS among dialysis atients, esumably due to the outine use of ion sulementation in this oulation. 2,17 In ou study, 92.7% of all atients wee egulaly sulemented with ion, and this could have alleviated the effects of hemoglobin, ion, and feitin. The level of feitin was also not coelated with symtom seveity. Routine sulementation with ion could also exlain the lage ootion of atients with mild RLS (39.1%) in the RLS gou. Aging is also believed to be a isk facto fo idioathic RLS. 18 Howeve, evious studies have shown that this is not always tue in RLS atients undegoing dialysis. 19 The RLS atients in ou study tended to be younge, which suggests that RLS-inducing factos ae stonge than the aging effect in dialysis atients. Some studies have found a female eondeance in RLS, while othes have found no gende diffeence o even a ossible male edominance in RLS. 20,21 We found no female edominance in ou RLS atients. The duation of dialysis theay is geneally egaded as a isk facto fo RLS, 22 but this was not evident in ou study. We also could found no association between a high BMI and RLS in ou dialysis atients. 17,21 Daytime sleeiness as measued by the ESS did not diffe between the two gous in the esent study, which is inconsistent with evious eots. 3,23 Since ou study oulation included many diabetic atients, the accomanying etinoathy evented us fom obtaining accuate ESS scoes because such atients ae unable to dive a ca, watch TV, o ead newsaes. Theefoe, this might not be an aoiate modality fo assessing slee distubance in diabetic atients. A evious study suggested that the evalence of RLS among dialysis atients in Koea was 44.0%. 24 The lowe evalence found in ou study might be due to ou method of face-to-face questioning combined with a neuological examination yielding moe accuate diagnoses than those based on questionnaies and diffeent biological oeties, includeing age and duation of dialysis. Questionnaie-based diagnoses of RLS might be uneliable in uemic atients due to low sensitivity and secificity. 25 False-ositive esults aea to be caused by the esence of othe leg-elated symtoms and neuologically objective signs suggestive of eiheal neuoathy. 25 Ou study had some limitations. The fist is the inevitable selection bias fom collecting data fom only 164 out of a total of 321 atients. The main cause of exclusion was communication difficulties, which might have excluded all of the most sevee atients. The second limitation was insufficient data on medication histoy. Ou atients wee taking many dugs, including benzodiazeines, gabaentin, ticyclic antideessants, and calcium-channel antagonists, and we could not ule out thei ole in RLS. Finally, we did not obtain data on neve conduction aametes because most of the atients did not agee to undego such investigations. Howeve, we attemted to exclude othe diseases that could mimic RLS by efoming a stuctued inteview and neuological examination. RLS is common in atients undegoing egula hemodialysis. Moe attention to this disease might aid its detection and educe atient discomfot. Futhe studies ae needed to disclose its detailed isk factos and the athohysiological ole of the BUN level in RLS. REFERENCES 1. Waltes AS. Towad a bette definition of the estless legs syndome. The Intenational Restless Legs Syndome Study Gou. Mov Disod 1995;10: Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndome in atients on dialysis. 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