• Effect of exercise training and dopamine agonists in patients with uremic restless legs syndrome: A six-month randomized, partially double-blind, placebo-controlled comparative study

      Giannaki, CD; Sakkas, GK; Karatzaferi, C; Hadjigeorgiou, GM; Lavdas, E; Kyriakides, T; Koutedakis, Y; Stefanidis, I; Department of Nephrology, School of Medicine, University of Thessaly, Larissa, Greece. gsakkas@med.uth.gr. (Springer Science and Business Media LLC, 2013-09-11)
      Background: Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes' severity and quality of life. Methods. In this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: 1) the exercise training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months. Restless Legs Syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by Dual Energy X Ray Absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires. Results: Exercise training and dopamine agonists were effective in reducing syndrome's symptoms by 46% (P = 0.009) and 54% (P = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (P < 0.05), however, only the dopamine agonists significantly improved sleep quality (P = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (P = 0.014), which also reduced fat infiltration in muscles (P = 0.044) and improved physical performance (P > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (P = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (P = 0.016). Conclusions: A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS. Trial registration. NCT00942253. © 2013 Giannaki et al.; licensee BioMed Central Ltd.
    • Evidence of blood and muscle redox status imbalance in experimentally induced renal insufficiency in a rabbit model

      Poulianiti, KP; Karioti, A; Kaltsatou, A; Mitrou, GI; Koutedakis, Y; Tepetes, K; Christodoulidis, G; Giakas, G; Maridaki, MD; Stefanidis, I; et al. (Hindawi Limited, 2019-04-04)
      Chronic kidney disease (CKD) is accompanied by a disturbed redox homeostasis, especially in end-stage patients, which is associated with pathological complications such as anemia, atherosclerosis, and muscle atrophy. However, limited evidence exists about redox disturbances before the end stage of CKD. Moreover, the available redox literature has not yet provided clear associations between circulating and tissue-specific (muscle) oxidative stress levels. The aim of the study was to evaluate commonly used redox status indices in the blood and in two different types of skeletal muscle (psoas, soleus) in the predialysis stages of CKD, using an animal model of renal insufficiency, and to investigate whether blood redox status indices could be reflecting the skeletal muscle redox status. Indices evaluated included reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PC), and thiobarbituric acid reactive substances (TBARS). Results showed that blood GSH was higher in the uremic group compared to the control (17.50 ± 1.73 vs. 12.43 ± 1.01, p = 0.033). In both muscle types, PC levels were higher in the uremic group compared to the control (psoas: 1.086 ± 0.294 vs. 0.596 ± 0.372, soleus: 2.52 ± 0.29 vs. 0.929 ± 0.41, p < 0.05). The soleus had higher levels of TBARS, PC, GSH, CAT, and GR and lower TAC compared to the psoas in both groups. No significant correlations in redox status indices between the blood and skeletal muscles were found. However, in the uremic group, significant correlations between the psoas and soleus muscles in PC, GSSG, and CAT levels emerged, not present in the control. Even in the early stages of CKD, a disturbance in redox homeostasis was observed, which seemed to be muscle type-specific, while blood levels of redox indices did not seem to reflect the intramuscular condition. The above results highlight the need for further research in order to identify the key mechanisms driving the onset and progression of oxidative stress and its detrimental effects on CKD patients.
    • Evidence of increased muscle atrophy and impaired quality of life parameters in patients with Uremic restless legs syndrome

      Giannaki, CD; Sakkas, GK; Karatzaferi, C; Hadjigeorgiou, GM; Lavdas, E; Liakopoulos, V; Tsianas, N; Koukoulis, GN; Koutedakis, Y; Stefanidis, I; et al. (Public Library of Science (PLoS), 2011-10-03)
      Background: Restless Legs Syndrome is a very common disorder in hemodialysis patients. Restless Legs Syndrome negatively affects quality of life; however it is not clear whether this is due to mental or physical parameters and whether an association exists between the syndrome and parameters affecting survival. Methodology/Principal Findings: Using the Restless Legs Syndrome criteria and the presence of Periodic Limb Movements in Sleep (PLMS/h >15), 70 clinically stable hemodialysis patients were assessed and divided into the RLS (n = 30) and non-RLS (n = 40) groups. Physical performance was evaluated by a battery of tests: body composition by dual energy X ray absorptiometry, muscle size and composition by computer tomography, while depression symptoms, perception of sleep quality and quality of life were assessed through validated questionnaires. In this cross sectional analysis, the RLS group showed evidence of thigh muscle atrophy compared to the non-RLS group. Sleep quality and depression score were found to be significantly impaired in the RLS group. The mental component of the quality of life questionnaire appeared significantly diminished in the RLS group, reducing thus the overall quality of life score. In contrast, there were no significant differences between groups in any of the physical performance tests, body and muscle composition. Conclusions: The low level of quality of life reported by the HD patients with Restless Legs Syndrome seems to be due mainly to mental health and sleep related aspects. Increased evidence of muscle atrophy is also observed in the RLS group and possibly can be attributed to the lack of restorative sleep. © 2011 Giannaki et al.
    • Uremic myopathy: Is oxidative stress implicated in muscle dysfunction in uremia?

      Kaltsatou, A; Sakkas, GK; Poulianiti, KP; Koutedakis, Y; Tepetes, K; Christodoulidis, G; Stefanidis, I; Karatzaferi, C; Department of Physical Education and Sport Sciences (DPESS), School of Physical Education (PE), University of Thessaly Trikala, Greece. (Frontiers Media SA, 2015-03-30)
      Renal failure is accompanied by progressive muscle weakness and premature fatigue, in part linked to hypokinesis and in part to uremic toxicity. These changes are associated with various detrimental biochemical and morphological alterations. All of these pathological parameters are collectively termed uremic myopathy. Various interventions while helpful can't fully remedy the pathological phenotype. Complex mechanisms that stimulate muscle dysfunction in uremia have been proposed, and oxidative stress could be implicated. Skeletal muscles continuously produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) at rest and more so during contraction. The aim of this mini review is to provide an update on recent advances in our understanding of how ROS and RNS generation might contribute to muscle dysfunction in uremia. Thus, a systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. While few studies met our criteria their findings are discussed making reference to other available literature data. Oxidative stress can direct muscle cells into a catabolic state and chronic exposure to it leads to wasting. Moreover, redox disturbances can significantly affect force production per se. We conclude that oxidative stress can be in part responsible for some aspects of uremic myopathy. Further research is needed to discern clear mechanisms and to help efforts to counteract muscle weakness and exercise intolerance in uremic patients.