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      The Uremic Environment and Muscle Dysfunction in Man and Rat

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          Background: Patients reaching end-stage renal disease experience debilitating fatigue, with progression of this disease, rendering patients dysfunctional in their everyday lives. Methods: In vivomeasurements of muscle function, assessed using surface electromyography (EMG), were made on 25 patients prior to and after a session of hemodialysis (HD) treatment, alongsidein vitro measurements of muscle function in isolated rat muscles incubated in normal or uremic conditions approximating to those found in uremic rats (rat uremic: RU) or uremic humans (human uremic: HU). Results: HD significantly affected plasma values, e.g. reducing urea (69%), creatinine (62%), potassium (23%) and phosphate (48%) concentrations in patients (all p < 0.01). Treatment also improved the EMG frequency of 2nd dorsal interosseous (fast-twitch) (p < 0.01), although no change was noted for vastus lateralis (slow-twitch). In isolated rat muscles, a uremic environment had no significant effect on slow-twitch soleus during field stimulation, however, in fast-twitch extensor digitorum longus, a significant 23% (RU) and 22% (HU) faster rate of decline in force was measured, compared to controls (p < 0.001 and p < 0.01, respectively). Conclusion: It is concluded that (1) muscle weakness and its electrophysiological correlates may be rapidly induced by uremic solutes and rapidly reversed when the solutes are removed by dialysis, and (2) fast-twitch muscles are more readily affected by uremic conditions than slow-twitch muscles.

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          Most cited references 16

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          The quality of life of patients with end-stage renal disease.

          We assessed the quality of life of 859 patients undergoing dialysis or transplantation, with the goal of ascertaining whether objective and subjective measures of the quality of life were influenced by case mix or treatment. We found that 79.1 per cent of the transplant recipients were able to function at nearly normal levels, as compared with between 47.5 and 59.1 per cent of the patients treated with dialysis (depending on the type). Nearly 75 per cent of the transplant recipients were able to work, as compared with between 24.7 and 59.3 per cent of the patients undergoing dialysis. On three subjective measures (life satisfaction, well-being, and psychological affect) transplant recipients had a higher quality of life than patients on dialysis. Among the patients treated with dialysis, those undergoing treatment at home had the highest quality of life. All quality-of-life differences were found to persist even after the patient case mix had been controlled statistically. Finally, the quality of life of transplant recipients compared well with that of the general population, but despite favorable subjective assessments, patients undergoing dialysis did not work or function at the same level as people in the general population.
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            The effects of exercise training on muscle atrophy in haemodialysis patients.

            Patients with end-stage renal disease on haemodialysis (HD) have limited work capacity. Many structural and functional alterations in skeletal muscles contribute to this disability. To evaluate the effects of exercise training on uraemic myopathy, seven HD patients (mean age 44.1+/-17.2 years) were studied. Open muscle biopsies were taken from their vastus lateralis muscle before and after a 6-month exercise rehabilitation programme and examined by routine light- and transmission electron-microscopy. Histochemical stainings of frozen sections were performed and morphometric analysis was also applied to estimate the proportion of each fibre type and the muscle fibre area. Spiroergometric and neurophysiological testing and peak extension forces of the lower limbs were measured before and after exercise training. All patients showed impaired exercise capacity, which was associated with marked muscular atrophy (mean area 2548+/-463 microm2) and reduction in muscle strength and nerve conduction velocity. All types of fibres were atrophied, but type II were more affected. The ultrastructural study showed severe degenerative changes in skeletal muscle fibres, mitochondria, and capillaries. Exercise training had an impressive effect on muscular atrophy; in particular the proportion of type II fibres increased by 51% and mean muscle fibre area by 29%. Favourable changes were also seen on the structure and number of capillaries and mitochondria. These results were confirmed by a 48% increase in VO2 peak and a 29% in exercise time, as well as an improvement in the peak muscle strength of the lower limbs and in nerve conduction velocity. Skeletal muscle atrophy in HD patients contribute to their poor exercise tolerance. The application of an exercise training rehabilitation programme improved muscle atrophy markedly, and therefore had beneficial effects in overall work performance.
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              Exercise Training and the Progression of Chronic Renal Failure

              The possible beneficial effect of regular exercise training on the progression of chronic renal failure was studied in a prospective randomized controlled study. Thirty patients with a median glomerular filtration rate (GFR) of 25 ml/(min·1.73 m 2 ) (range 10-43) were randomized to physical training (30 min of bicycling daily or an equal amount of other physical activities) or to maintenance of the usual lifestyle. The median maximal work capacity increased significantly in the exercise group and remained unchanged in the control group during a median observation time of 20 months whereas the rate of progression judged by the slope of GFR versus time plot was equal in the two groups. Hence, the beneficial effect of exercise training, earlier observed in rat studies, could not be reproduced in our patients. Physical exercise had no untoward effect on progression of renal disease.

                Author and article information

                Nephron Physiol
                Nephron Physiology
                S. Karger AG
                April 2006
                11 April 2006
                : 103
                : 1
                : p33-p42
                aInstitute of Anatomy and Physiology, The Royal Veterinary and Agricultural University, Frederiksberg, bDepartment of Nephrology, Herlev University Hospital, Herlev, cDialysis Ward, Hillerød Hospital, Hillerød, and dThe Danish Library of Science and Medicine, Copenhagen University, Copenhagen, Denmark
                90221 Nephron Physiol 2006;103:p33–p42
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 3, References: 30, Pages: 1
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                Original Paper

                Cardiovascular Medicine, Nephrology

                Muscle strength, Dialysis, Electromyography, Uremia, Muscle dysfunction


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