Christoforos D. Giannaki

Evidence of Increased Muscle Atrophy and Impaired Quality of Life Parameters in Patients with Uremic Restless Legs Syndrome

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. Methodοlogy/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.

Epidemiology, impact, and treatment options of restless legs syndrome in end-stage renal disease patients: an evidence-based review

Restless legs syndrome (RLS) (or Willis-Ekbom disease) is a neurological disorder with high prevalence among the end-stage renal disease population. This is one of the most predominant types of secondary RLS, and it is called uremic RLS. Despite the fact that uremic RLS has been less studied compared to idiopathic RLS, recent studies now shed light in many aspects of the syndrome including clinical characteristics, impact, epidemiology, and treatment options. The current review discusses the above topics with special emphasis given on the management of uremic RLS, including the management of symptoms that often appear during a hemodialysis session. Uremic RLS symptoms may be ameliorated by using pharmacological and nonpharmacological treatments. Evidence so far shows that both approaches may be effective in terms of reducing the RLS symptoms severity; nevertheless, more research is needed on the efficiency of treatments for uremic RLS.

Periodic Limb Movements in Sleep Contribute to Further Cardiac Structure Abnormalities in Hemodialysis Patients with Restless Legs Syndrome

STUDY OBJECTIVES In hemodialysis (HD) patients, restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) constitute common sleep disorders. Recent findings indicate a role for PLMS as a risk factor in the development of new or the aggravation of existing cardiovascular disease. The aim of the current study was to investigate the association of PLMS with indices of cardiac morphology and function in HD patients with RLS as a potential pathway by which PLMS could alter cardiovascular risk. METHODS Based on PLMS diagnosis by an overnight polysomnographic evaluation, 19 stable HD-RLS patients were divided into the PLMS group (n = 10) and the non-PLMS group (n = 9). During the overnight assessment, nocturnal blood pressure (BP) indices were also assessed. Left ventricular (LV) dimensions were examined by M-mode echocardiography, whereas LV diastolic function was evaluated by conventional Doppler and tissue Doppler imaging the following day. RESULTS LV internal diameter in diastole was significantly increased in the PLMS group (4.96 ± 0.61 vs 4.19 ± 0.48 cm, p = 0.007), leading to a significantly increase in LV mass (202 ± 52 vs 150 ± 37 g, p = 0.026). In contrast, no between group differences were observed in diastolic function indices (p > 0.05). CONCLUSIONS These are the first data to associate severe PLMS with further LV structure abnormalities in HD patients with RLS.

Non-pharmacological management of periodic limb movements during hemodialysis session in patients with uremic restless legs syndrome

Restless legs syndrome (RLS) is very common in hemodialysis patients. RLS induces motor excitability and discomfort during rest periods, and those symptoms have also been observed during hemodialysis sessions. The aim of the study was to assess whether a single bout of exercise could reduce periodic limb movements (PLM) occurring during hemodialysis. Eighteen hemodialysis patients were eligible and participated in the study. Using the RLS criteria and further verified by the presence of PLM during sleep, patients were divided to non-RLS and RLS groups. Three scenarios were studied during three different sessions: 1) light exercise, including cycling for 45 minutes with no added resistance, 2) heavy exercise, including cycling for 45 minutes with a resistance set at 60% of their exercise capacity, and 3) no exercise, including rest for the same period of time. In all sessions, PLM per hour of hemodialysis (PLM/hHD) was recorded. A single bout of either light or heavy exercise was equally effective in significantly reducing PLM/hHD in patients with RLS compared with the no-exercise scenario, whereas in non-RLS patients, no effect was observed. Independent of intensity, a single bout of intradialytic exercise reduces PLM/hHD in hemodialysis patients with RLS. Further research is needed to establish the acute role of exercise in ameliorating the RLS symptoms.

Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability

Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95% CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: −4.09, −2.55). Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels.

Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients

Hemodialysis patients exhibit insulin resistance (IR) in target organs such as liver, muscles, and adipose tissue. The aim of this study was to identify contributors to IR and to develop a model for predicting glucose intolerance in nondiabetic hemodialysis patients. After a 2-h, 75-g oral glucose tolerance test (OGTT), 34 hemodialysis patients were divided into groups with normal (NGT) and impaired glucose tolerance (IGT). Indices of insulin sensitivity were derived from OGTT data. Measurements included liver and muscle fat infiltration and central adiposity by computed tomography scans, body composition by dual energy X-ray absorptiometer, sleep quality by full polysomnography, and functional capacity and quality of life (QoL) by a battery of exercise tests and questionnaires. Cut-off points, as well as sensitivity and specificity calculations were based on IR (insulin sensitivity index by Matsuda) using a receiver operator characteristics (ROC) curve analysis. Fifteen patients were assigned to the IGT, and 19 subjects to the NGT group. Intrahepatic fat content and visceral adiposity were significantly higher in the IGT group. IR indices strongly correlated with sleep disturbances, visceral adiposity, functional capacity, and QoL. Visceral adiposity, O2 desaturation during sleep, intrahepatic fat content, and QoL score fitted into the model for predicting glucose intolerance. A ROC curve analysis identified an intrahepatic fat content of > 3.97% (sensitivity, 100; specificity, 35.7) as the best cutoff point for predicting IR. Visceral and intrahepatic fat content, as well as QoL and sleep seemed to be involved at some point in the development of glucose intolerance in hemodialysis patients. Means of reducing fat depots in the liver and splachnic area might prove promising in combating IR and cardiovascular risk in hemodialysis patients.

Exercise Training and Depression in ESRD: A Review

Depression, a mental disorder with a high personal, societal, and economic impact, affects at least 20–30% of patients receiving hemodialysis therapy. It is associated with a high mortality rate, low adherence to medication, and a low perceived quality of life. Exercise training is a promising nonpharmacological intervention that can be safely applied to these patients. Beyond the well‐publicized physiological benefits of exercise training, a number of studies have focused on the effects of exercise training on mental factors and quality of life parameters including its less appreciated effects on depression symptoms. This evidence‐based review article reviews and discusses the effects of exercise training on depression in end‐stage renal disease patients.

Uremic versus idiopathic restless legs syndrome: impact on aspects related to quality of life.

Restless legs syndrome (RLS) affects both the general population and patients with chronic renal failure. Even though it has been suggested that all forms of RLS share a common pathophysiology, not much evidence exists on how RLS of different etiology could affect aspects related to quality of life (QoL). The aim of this study was to investigate whether patients with uremic RLS (uRLS) experience lower QoL, mental health, and sleep quality, compared with their idiopathic RLS (iRLS) counterparts. Fifteen iRLS patients, 26 uRLS patients, and 15 age-matched healthy individuals participated in the study. The RLS diagnosis and severity, the depression levels, the perception of sleep, and perceived health-related QoL levels were assessed through validated questionnaires. Sleep status was not different between the two RLS groups. In contrast, the uRLS patients scored higher in RLS symptoms severity, depression, while they scored lower in QoL levels compared with iRLS patients. QoL levels were significantly lower in both RLS groups compared with healthy individuals. In conclusion, the uRLS patients experienced lower QoL levels and more severe RLS symptoms, compared with the idiopathic group, possibly leading to the observed higher depression symptoms score.

Periodic limb movements in sleep and cardiovascular disease: time to act

Periodic limb movements in sleep (PLMS) is a common sleep disorder in both the general population and in patients with chronic diseases such as patients receiving hemodialysis therapy. PLMS can be assessed during an overnight polysomnographic examination and are described as repetitive, stereotypical, and unconscious leg movements that occur during sleep. It is noteworthy, that PLMS are present in up to 80% of patients with a condition occurring during wakefulness, called restless legs syndrome (RLS). Indeed, the presence of PLMS is considered to be one of the supportive criteria for the diagnosis of the later condition (1). PLMS may also occur in patients with sleep apnea, narcolepsy, and rapid eye movement behavior disorder or even can be present in patients without any sleep or medical-related pathological condition, and especially in the elderly (2). PLMS could cause significant sleep disturbance and result in non-restorative sleep via its associated arousals and motor restlessness. It is logical then to assume that as PLMS interferes with the expected sleep associated dipping of blood pressure (3), it may constitute a risk factor for cardiac disease and mortality. Notably, a role of PLMS as a predictor of mortality has been proposed in small survival study by Benz et al. (4) in which PLMS was strongly and independently associated with mortality in renal patients. Recently direct observations on cardiac structure added strong support on the association between the severity of PLMS and cardiovascular (CV) mortality and morbidity first in secondary RLS by us (5) and then verified in idiopathic RLS patients (6) as well.

The relationship between physical fitness and obesity among a sample of adolescents in Cyprus

Abstract Recent data revealed that adolescent obesity appeared to be a rising problem in Cyprus. However, there is a scarcity of published data regarding fitness-related parameters, which could contribute for the presence of obesity in Cyprus’ adolescence population. The aim of the current study was to investigate the association between adolescent obesity, body composition, and fitness levels. A total of 270 high school students volunteered to participate in this cross-sectional study. Body mass and height were assessed in order to calculate body mass index, while body fat percentage was calculated by using bioelectrical impedance analysis. Physical fitness parameters were assessed through a battery of field tests. Body fat was inversely associated with cardiorespiratory fitness levels, sprint and jumping performance, as well as with the frequency of physical education class sessions per week (p<0.05). The adolescents with high body fat were found to exhibit significant reductions in all the fitness related parameters (p<0.05), except with the arm strength (p>0.05). This study is the first to uncover an inverse association between high body fat and fitness-related parameters among a sample of adolescents in Cyprus. These data can be used in order to develop effective interventions aiming to counterbalance obesity and improve the overall health and the quality of life of adolescents.