A single-blind randomized controlled trial to evaluate the effect of 6 months of progressive aerobic exercise training in patients with uraemic restless legs syndrome.

BACKGROUND: Uraemic restless legs syndrome (RLS) affects a significant proportion of patients receiving haemodialysis (HD) therapy. Exercise training has been shown to improve RLS symptoms in uraemic RLS patients; however, the mechanism of exercise-induced changes in RLS severity is still unknown. The aim of the current randomized controlled exercise trial was to investigate whether the reduction of RLS severity, often seen after training, is due to expected systemic exercise adaptations or it is mainly due to the relief that leg movements confer during exercise training on a cycle ergometer. This is the first randomized controlled exercise study in uraemic RLS patients. METHODS: Twenty-four RLS HD patients were randomly assigned to two groups: the progressive exercise training group (n = 12) and the control exercise with no resistance group (n = 12). The exercise session in both groups included intradialytic cycling for 45 min at 50 rpm. However, only in the progressive exercise training group was resistance applied, at 60-65% of maximum exercise capacity, which was reassessed every 4 weeks to account for the patients' improvement. The severity of RLS symptoms was evaluated using the IRLSSG severity scale, functional capacity by a battery of tests, while sleep quality, depression levels and daily sleepiness status were assessed via validated questionnaires, before and after the intervention period. RESULTS: All patients completed the exercise programme with no adverse effects. RLS symptom severity declined by 58% (P = 0.003) in the progressive exercise training group, while a no statistically significant decline was observed in the control group (17% change, P = 0.124). Exercise training was also effective in terms of improving functional capacity (P = 0.04), sleep quality (P = 0.038) and depression score (P = 0.000) in HD patients, while no significant changes were observed in the control group. After 6 months of the intervention, RLS severity (P = 0.017), depression score (P = 0.002) and daily sleepiness status (P = 0.05) appeared to be significantly better in the progressive exercise group compared with the control group. CONCLUSION: A 6-month intradialytic progressive exercise training programme appears to be a safe and effective approach in reducing RLS symptom severity in HD patients. It seems that exercise-induced adaptations to the whole body are mostly responsible for the reduction in RLS severity score, since the exercise with no applied resistance protocol failed to improve the RLS severity status of the patients.

Nocturnal Activity Is Not Affected by a Long-Duration, Low-Intensity Single Exercise Bout.

The aim of the current study was to examine whether prolonged low-intensity aerobic exercise could affect nocturnal activity in healthy individuals. Twenty-one healthy adults (24 ± 3.7 years; 9 females) were enrolled in this study. All participants participated in a 3-h low-intensity walking exercise protocol. Standard biochemical indices were assessed before the exercise protocol and at 72 h. Nocturnal activity and various indices of health were recorded for five consecutive days. The score of muscle pain peaked the night after the exercise protocol (p < 0.05) and returned to baseline two days after. No statistical differences were found in any of the parameters examined, including nocturnal activity. Prolonged low-intensity exercise does not affect nocturnal activity. The anecdotal reports suggesting that exercise or/and physical activity could worsen symptoms of motor restlessness during sleep in sleep disorders, such as restless legs syndrome and periodic limb movements, are not supported by this study. However, these findings need to be verified in clinical populations, as well as by using protocols with different forms of exercise.

Evidence of Blood and Muscle Redox Status Imbalance in Experimentally Induced Renal Insufficiency in a Rabbit Model.

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.

Combination of Exercise Training and Dopamine Agonists in Patients with RLS on Dialysis: A Randomized, Double-Blind Placebo-Controlled Study.

Both exercise training and treatment with dopamine agonists (DA) have been used with success for the amelioration of uremic restless legs syndrome (RLS) symptoms. However, no data are available combining those two approaches. The aim of the current randomized, double-blind, placebo-controlled study was to investigate the effects of a 6 month intradialytic exercise training in combination with a low dose of DA in patients suffering from uremic RLS symptoms. Fourteen stable patients with RLS on hemodialysis were randomly assigned to the exercise training plus DA group and the exercise training plus placebo group. Both combinations were found to equally reduce uremic RLS symptoms by approximately 60%. The combination of low dose of DA with aerobic exercise training could be considered an alternative approach to high DA dosage regimes in reducing RLS symptoms' severity.

Intradialytic aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study.

We present the first study on the influence of exercise training on restless legs syndrome (RLS) in patients on hemodialysis (HD). Restless legs syndrome has been treated pharmacologically with satisfactory results; however, side effects and rebound phenomena have been reported. Intradialytic exercise training effectively counteracts uremia-induced catabolism; nevertheless, it remains unknown whether patients with RLS undergoing HD benefit from such programs. The aims of the current study were to evaluate the effect of 16-weeks aerobic exercise training in the severity of RLS and in the functional capacity and the quality of life of patients with RLS on HD. Fourteen patients on HD (four female, mean age 59 +/- 16 years) with untreated RLS were assigned, according to their will, to either the exercise group (Ex-group, n = 7), and participated in a 16-week supervised intradialytic aerobic exercise training, or to the control group (Con-group, n = 7), and continued usual activities. Primary aim was to compare the International RLS (IRLS) study group rating scale, functional ability, and quality of life in baseline and the end of the 16 weeks. Exercise training reduced IRLS score by 42% (p = 0.02). Furthermore, it significantly improved indices of functional ability (p = 0.02), exercise capacity (p = 0.01), quality of life (p = 0.03), and sleep quality (p = 0.01). In the Con-group no changes were observed. In conclusion, aerobic exercise training is safe and efficacious in reducing RLS symptoms and improving quality of life in patients with RLS on HD.

Haemodialysis patients with sleep apnoea syndrome experience increased central adiposity and altered muscular composition and functionality.

BACKGROUND: Sleep apnoea frequently affects patients with end-stage renal disease. However, it is still unclear whether or to what extent sleep disorders may affect functional capacity and quality of life in haemodialysis patients. We tested the hypothesis that apneic dialysis patients due to the lack of restorative sleep will have a further reduced functional capacity and further compromised quality of life compared to their non-apneic counterparts. METHODS: Forty-three clinically stable haemodialysis patients (13 F, 56.6+/-19.4 years) were examined. After polysomnographic analysis, patients were divided in two groups according to their calculated apnoea hypopnoea index (AHI; cutoff 5). Primary outcomes were intergroup differences in the following: (1) physical capacity and muscle performance, assessed by functional tests, (2) quality of life, assessed by the SF-36, (3) body composition, measured by DEXA and (4) muscle composition and size, as well as (5) visceral (VAT) and subcutaneous (SAT) adipose tissue, calculated by computed tomography. RESULTS: Twenty-two patients had AHI >5 (4 F, AHI=28.8+/-22.3). The adjusted analysis for age, BMI and years in dialysis therapy, showed that the low-AHI group (N=21, 9 F, AHI=1.8+/-1.3) had better functional capacity, and performed better in muscle strength and endurance tests compared to the high-AHI group. There were no differences in lean body mass and % total body fat between groups, however, values for VAT, VAT/TAT ratio and thigh muscles' fat infiltration were increased in the high-AHI group. VAT correlated with BMI (r=0.682, P=0.001), functional capacity (r=0.558, P=0.001) apnoea hypopnoea index (r=0.530, P=0.001). There were no statistical significant differences in quality of life between the two groups. To further account for age and BMI differences, a subgroup of patients was matched by age, sex and BMI (N=10/group). In the matched analysis, all the above statistical differences remained, between the low-AHI and high-AHI groups. CONCLUSIONS: Haemodialysis patients with sleep apnoea syndrome demonstrate poorer functional capacity, physical performance and muscle composition, compared to non-apneic dialysis patients. Overall, sleep apnoea appears to partly contribute to the total diminished functional capacity of haemodialysis patients.

Polysomnographic evidence of sleep apnoea disorders in lean and overweight haemodialysis patients.

BACKGROUND: Sleep apnoea disorders affect a large proportion of patients with renal failure. However, it is unknown whether body composition and visceral adiposity predispose haemodialysis patients to sleep apnoea disorders. METHODS: Forty-one dialysis patients were divided in two groups according to the BMI score as; the Lean group (N=21, 1F/20M, BMI = 21.3 +/- 2.1) and the Overweight group (N=20, 9F/11M, BMI = 28.3 +/- 2.8). Sleep disturbances assessed by a full polysomnography (PSG), visceral adipose tissue (VAT), calculated by computed tomography, the quality of life, assessed by the SF-36, and the body composition, measured by DEXA. RESULTS: None of the PSG parameters were different between the two groups. Only visceral adiposity was correlated significantly with sleep apnoea disorders. CONCLUSIONS: BMI and percent of total body fat do not seem to predispose for sleep apnoea disorders. Rather it is the increased fat deposition in abdominal area that plays the pivotal role.