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      Uremic Restless Legs Syndrome (RLS) and Sleep Quality in Patients With End-Stage Renal Disease on Hemodialysis: Potential Role of Homocysteine and Parathyroid Hormone

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          Abstract

          Background: The aetiology of uremic restless legs syndrome (RLS) remains unclear. Our research investigated whether an elevated plasma concentration of the excitatory amino acid homocysteine might be associated with RLS occurrence in patients with chronic renal insufficiency on hemodialysis. Methods: Total plasma homocysteine as well as creatinine, urea, folate, parathyroid hormone, hemoglobin, iron, ferritin, phosphate, calcium, magnesium, and albumin levels were compared between 26 RLS-affected (RLSpos) and 26 non-affected (RLSneg) patients on chronic hemodialysis. We further compared subjective sleep quality between RLSpos and RLSneg patients using the Pittsburgh-Sleep-Quality-Index and investigated possible relationships between laboratory parameters and sleep quality. Results: Taking individual albumin concentrations into account, a significant positive correlation between total plasma homocysteine and RLS occurrence was observed (r= 0.246; p=0.045). Sleep quality was significantly more reduced in RLSpos compared to RLSneg patients and RLS severity correlated positively with impairment of sleep quality. Bad sleep quality in all patients was associated with higher concentrations of parathyroid hormone. Conclusion: Our results suggest a possible aetiological role of homocysteine in uremic RLS. They confirm that uremic RLS is an important factor causing sleep impairment in patients on hemodialysis. Higher parathyroid hormone levels might also be associated with bad sleep quality in these patients.

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          Most cited references15

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          Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome.

          (2003)
          There is a need for an easily administered instrument which can be applied to all patients with restless legs syndrome (RLS) to measure disease severity for clinical assessment, research, or therapeutic trials. The pathophysiology of RLS is not clear and no objective measure so far devised can apply to all patients or accurately reflect severity. Moreover, RLS is primarily a subjective disorder. Therefore, a subjective scale is at present the optimal instrument to meet this need. Twenty centers from six countries participated in an initial reliability and validation study of a rating scale for the severity of RLS designed by the International RLS study group (IRLSSG). A ten-question scale was developed on the basis of repeated expert evaluation of potential items. This scale, the IRLSSG rating scale (IRLS), was administered to 196 RLS patients, most on some medication, and 209 control subjects. The IRLS was found to have high levels of internal consistency, inter-examiner reliability, test-retest reliability over a 2-4 week period, and convergent validity. It also demonstrated criterion validity when tested against the current criterion of a clinical global impression and readily discriminated patient from control groups. The scale was dominated by a single severity factor that explained at least 59% of the pooled item variance. This scale meets performance criteria for a brief, patient completed instrument that can be used to assess RLS severity for purposes of clinical assessment, research, or therapeutic trials. It supports a finding that RLS is a relatively uniform disorder in which the severity of the basic symptoms is strongly related to their impact on the patient's life. In future studies, the IRLS should be tested against objective measures of RLS severity and its sensitivity should be studied as RLS severity is systematically manipulated by therapeutic interventions.
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            Insomnia in maintenance haemodialysis patients.

            Studies in the last 15 years have shown a high prevalence of sleep disorders in maintenance haemodialysis (HD) patients. To investigate whether the new technical and therapeutic advances of the last decade have had a positive impact on sleep disturbances in HD patients: 694 patients (384 males, 310 females) were surveyed using a specific questionnaire; their clinical, lifestyle and dialysis data were also recorded. Forty-five per cent of patients (n=311; 156 males, 155 females) complained of insomnia, defined either by delayed sleep onset and/or night-time waking, and were included in the insomnia group; the remainder were used as controls (control group). There was a significantly higher risk of insomnia in patients with >12 months on dialysis, in patients dialysed in the morning (P<0.003), and in patients with higher parathyroid hormone (PTH) levels (P<0.05). Body mass index, body weight gain and blood pressure did not differ between the groups, and neither did the dialysis parameters. Creatinine and urea plasma levels were higher in the control group vs the insomnia group (P<0.001), but there was no difference in haemoglobin concentrations or use of erythropoietin, calcitriol and antihypertensive drugs. Cigarette smoking, caffeine or alcohol intake were comparable in the two groups. The most frequently recorded sleep disorders were night-time waking (92%), trouble falling asleep (67%) and early morning waking (62%). Restless leg symptoms were described in 52% of patients with insomnia. The prevalence of insomnia in HD patients is still very high; elderly patients, and those with longer time on dialysis and high levels of PTH are at major risk of insomnia, whereas type of dialysis, haemoglobin levels and behavioural factors do not seem to play a critical role in determining this sleep disorder.
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              Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome.

              Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and generate periodic limb movements; iron deficiency may be a main predisposing factor of augmentation, probably caused by a reduced function of the dopamine transporter; therapy with levodopa or dopamine agonists should remain at low doses and; iron supplementation and opiates are the therapy of choice to counter augmentation.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2013
                November 2013
                25 October 2013
                : 37
                : 4-5
                : 458-463
                Affiliations
                aDepartment of Psychiatry and Psychotherapy, Georg-August-University Göttingen; bInterdisciplinary Emergency Care Unit, Georg-August-University Göttingen; cDepartment of Child and Adolescent Psychiatry, Georg-August-University Göttingen, Göttingen; dClinic of Sleep Medicine, St.Hedwig Krankenhaus, Berlin, Germany
                Author notes
                *Katrin Gade, Department of Psychiatry and Psychotherapy,, Georg-August-University Göttingen, Von-Siebold-Str. 5, D-37075 Göttingen (Germany), Tel. +49-551-39 6610, Fax +49-551-39 9337, E-Mail katrin gade@med uni-goettingen de
                Article
                355727 Kidney Blood Press Res 2013;37:458-463
                10.1159/000355727
                24247595
                5aaa1ad8-a544-4636-a7cb-affdcd592a25
                © 2013 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 23 September 2013
                Page count
                Pages: 6
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Homocysteine,Dialysis,Uremic RLS,Sleep Quality,Parathyroid hormone
                Cardiovascular Medicine, Nephrology
                Homocysteine, Dialysis, Uremic RLS, Sleep Quality, Parathyroid hormone

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