Browsing by Author "Watson, Emma L."
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- Combined walking exercise and alkali therapy in patients with CKD4–5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expressionPublication . Watson, Emma L.; Kosmadakis, George C.; Smith, Alice C.; Viana, Joao L.; Brown, Jeremy R.; Molyneux, Karen; Pawluczyk, Izabella Z. A.; Mulheran, Michael; Bishop, Nicolette C.; Shirreffs, Susan; Maughan, Ronald J.; Owen, Paul J.; John, Stephen G.; McIntyre, Christopher W.; Feehally, John; Bevington, AlanMuscle-wasting in chronic kidney disease (CKD) arises from several factors including sedentary behaviour and metabolic acidosis. Exercise is potentially beneficial but might worsen acidosis through exercise-induced lactic acidosis. We studied the chronic effects of exercise in CKD stage 4-5 patients (brisk walking, 30 min, 5 times/week), and non-exercising controls; each group receiving standard oral bicarbonate (STD), or additional bicarbonate (XS) (Total n = 26; Exercising + STD n = 9; Exercising +XS n = 6; Control + STD n = 8; Control + XS n = 3). Blood and vastus lateralis biopsies were drawn at baseline and 6 months. The rise in blood lactate in submaximal treadmill tests was suppressed in the Exercising + XS group. After 6 months, intramuscular free amino acids (including the branched chain amino acids) in the Exercising + STD group showed a striking chronic depletion. This did not occur in the Exercising + XS group. The effect in Exercising + XS patients was accompanied by reduced transcription of ubiquitin E3-ligase MuRF1 which activates proteolysis via the ubiquitin-proteasome pathway. Other anabolic indicators (Akt activation and suppression of the 14 kDa actin catabolic marker) were unaffected in Exercising + XS patients. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methylhistidine output) was not observed. It is suggested that alkali effects in exercisers arose by countering exercise-induced acidosis. Whether further anabolic effects are attainable on combining alkali with enhanced exercise (e.g. resistance exercise) merits further investigation.
- Evidence for Anti-Inflammatory Effects of Exercise in CKDPublication . Viana, João L.; Kosmadakis, George C.; Watson, Emma L.; Bevington, Alan; Feehally, John; Bishop, Nicolette C.; Smith, Alice C.CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD.
- Muscle-Bone Crosstalk in Chronic Kidney Disease: The Potential Modulatory Effects of ExercisePublication . Leal, Diogo V.; Ferreira, Aníbal; Watson, Emma L.; Wilund, Kenneth R.; Viana, João L.Chronic kidney disease (CKD) is a prevalent worldwide public burden that increasingly compromises overall health as the disease progresses. Two of the most negatively affected tissues are bone and skeletal muscle, with CKD negatively impacting their structure, function and activity, impairing the quality of life of these patients and contributing to morbidity and mortality. Whereas skeletal health in this population has conventionally been associated with bone and mineral disorders, sarcopenia has been observed to impact skeletal muscle health in CKD. Indeed, bone and muscle tissues are linked anatomically and physiologically, and together regulate functional and metabolic mechanisms. With the initial crosstalk between the skeleton and muscle proposed to explain bone formation through muscle contraction, it is now understood that this communication occurs through the interaction of myokines and osteokines, with the skeletal muscle secretome playing a pivotal role in the regulation of bone activity. Regular exercise has been reported to be beneficial to overall health. Also, the positive regulatory effect that exercise has been proposed to have on bone and muscle anatomical, functional, and metabolic activity has led to the proposal of regular physical exercise as a therapeutic strategy for muscle and bone-related disorders. The detection of bone- and muscle-derived cytokine secretion following physical exercise has strengthened the idea of a cross communication between these organs. Hence, this review presents an overview of the impact of CKD in bone and skeletal muscle, and narrates how these tissues intrinsically communicate with each other, with focus on the potential effect of exercise in the modulation of this intercommunication.
- Peak aerobic capacity from incremental shuttle walk test in chronic kidney diseasePublication . Xenophontos, Soteris; Wilkinson, Thomas J.; Gould, Douglas W.; Watson, Emma L.; Viana, João L.; Smith, Alice C.Assessment of cardiorespiratory fitness is an important outcome in chronic kidney disease (CKD). We aimed to develop a predictive equation to estimate peak oxygen uptake (VO2peak ) and power output (WPeak ), as measured during a cardiopulmonary exercise test (CPET), from the distance walked (DW) during the incremental shuttle walk test (ISWT).
- Progressive Resistance Exercise Training in CKD: A Feasibility StudyPublication . Watson, Emma L.; Greening, Neil J.; Viana, João L.; Aulakh, Jaspreet; Bodicoat, Danielle H.; Barratt, Jonathan; Feehally, John; Smith, Alice C.Skeletal muscle wasting in chronic kidney disease (CKD) is associated with morbidity and mortality. Resistance exercise results in muscle hypertrophy in the healthy population, but is underinvestigated in CKD. We aimed to determine the feasibility of delivering a supervised progressive resistance exercise program in CKD, with secondary aims to investigate effects on muscle size, strength, and physical functioning.
- Response of the oxygen uptake efficiency slope to exercise training in patients with chronic kidney diseasePublication . Wilkinson, Thomas J.; Watson, Emma L.; Vadaszy, Noemi; Baker, Luke A.; Viana, João L.; Smith, Alice C.Chronic kidney disease (CKD) patients have poor cardiorespiratory fitness. Although cardiopulmonary exercise testing (CPET) is a universal assessment of cardiorespiratory fitness, values taken at 'peak' effort are strongly influenced by motivation and the choice of test endpoint. The oxygen uptake efficiency slope (OUES) integrates cardiovascular, musculoskeletal, and respiratory function into a single index to provide a more pragmatic and safer alternative to maximal testing. No research has explored whether exercise can improve the OUES in CKD patients.
- Test–retest reliability, validation, and “minimal detectable change” scores for frequently reported tests of objective physical function in patients with non-dialysis chronic kidney diseasePublication . Wilkinson, Thomas J.; Xenophontos, Soteris; Gould, Douglas W.; Vogt, Barbara P.; Viana, João L.; Smith, Alice C.; Watson, Emma L.Physical function is an important outcome in chronic kidney disease (CKD). We aimed to establish the reliability, validity, and the "minimal detectable change" (MDC) of several common tests used in renal rehabilitation and research. In a repeated measures design, 41 patients with CKD not requiring dialysis (stage 3b to 5) were assessed at an interval of 6 weeks. The tests were the incremental shuttle walk test (ISWT), "sit-to-stand" (STS) test, estimated 1 repetition maximum for quadriceps strength (e1RM), and VO2peak by cardiopulmonary exercise testing (CPET). Reliability was assessed using intraclass correlation coefficient and Bland-Altman analysis, and absolute reliability by standard error of measurement and MDC. The ISWT, STS-60, e1RM, and CPET had "good" to "excellent" reliability (0.973, 0.927, 0.927, and 0.866), respectively. STS-5 reliability was poor (0.676). The MDC is ISWT, 20 m; STS-5, 7.5 s; STS-60, 4 reps; e1RM, 6.4 kg; VO2peak, 2.8 ml/kg/min. There was strong correlation between the ISWT and VO2peak (r = 0.73 and 0.74). While there was poor correlation between the STS-5 and e1RM (r = 0.14 and 0.47), better correlation was seen between STS-5 and ISWT (r = 0.55 and 0.74). In conclusion, the ISWT, STS-60, e1RM, and CPET are reliable tests of function in CKD. The ISWT is a valid means of exercise capacity. The MDC can help researchers and rehabilitation professionals interpret changes following an intervention.
- The Effect of Resistance Exercise on Inflammatory and Myogenic Markers in Patients with Chronic Kidney DiseasePublication . Watson, Emma L.; Viana, Joao L.; Wimbury, David; Martin, Naomi; Greening, Neil J.; Barratt, Jonathan; Smith, Alice C.Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD) and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients. Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls. A sub-set of the cohort consented to vastus lateralis skeletal muscle biopsies (n = 10 exercise, n = 7 control) in which the inflammatory response (IL-6, IL-15, MCP-1 TNF-α), myogenic (MyoD, myogenin, myostatin), anabolic (P-Akt, P-eEf2) and catabolic events (MuRF-1, MAFbx, 14 kDa, ubiquitin conjugates) and overall levels of oxidative stress have been studied. Results: A large inflammatory response to unaccustomed exercise was seen with IL-6, MCP-1, and TNF-α all significantly elevated from baseline by 53-fold (P < 0.001), 25-fold (P < 0.001), and 4-fold (P < 0.001), respectively. This response was reduced following training with IL-6, MCP-1, and TNF-α elevated non-significantly by 2-fold (P = 0.46), 2.4-fold (P = 0.19), and 2.5-fold (P = 0.06), respectively. In the untrained condition, an acute bout of resistance exercise did not result in increased phosphorylation of Akt (P = 0.84), but this was restored following training (P = 0.01). Neither unaccustomed nor accustomed exercise resulted in a change in myogenin or MyoD mRNA expression (P = 0.88, P = 0.90, respectively). There was no evidence that resistance exercise training created a prolonged oxidative stress response within the muscle, or increased catabolism. Conclusions: Unaccustomed exercise creates a large inflammatory response within the muscle, which is no longer present following a period of training. This indicates that resistance exercise does not provoke a detrimental on-going inflammatory response within the muscle.
- Twelve-week combined resistance and aerobic training confers greater benefits than aerobic training alone in nondialysis CKDPublication . Watson, Emma L.; Gould, Douglas W.; Wilkinson, Thomas J.; Xenophontos, Soteris; Clarke, Amy L.; Vogt, Barbara Perez; Viana, João L.; Smith, Alice C.There is a growing consensus that patients with chronic kidney disease (CKD) should engage in regular exercise, but there is a lack of formal guidelines. In this report, we determined whether combined aerobic and resistance exercise would elicit superior physiological gains, in particular muscular strength, compared with aerobic training alone in nondialysis CKD. Nondialysis patients with CKD stages 3b-5 were randomly allocated to aerobic exercise {AE, n = 21; 9 men; median age 63 [interquartile range (IQR) 58-71] yr; median estimated glomerular filtration rate (eGFR) 24 (IQR 20-30) ml·min-1·1.73 m-2} or combined exercise [CE, n = 20, 9 men, median age 63 (IQR 51-69) yr, median eGFR 27 (IQR 22-32) ml·min-1·1.73 m-2], preceded by a 6-wk run-in control period. Patients then underwent 12 wk of supervised AE (treadmill, rowing, or cycling exercise) or CE training (as AE plus leg extension and leg press exercise) performed three times per week. Outcome assessments of knee extensor muscle strength, quadriceps muscle volume, exercise capacity, and central hemodynamics were performed at baseline, following the 6-wk control period, and at the end of the intervention. AE and CE resulted in significant increases in knee extensor strength of 16 ± 19% (mean ± SD; P = 0.001) and 48 ± 37% ( P < 0.001), respectively, which were greater after CE ( P = 0.02). AE and CE resulted in 5 ± 7% ( P = 0.04) and 9 ± 7% ( P < 0.001) increases in quadriceps volume, respectively ( P < 0.001), which were greater after CE ( P = 0.01). Both AE and CE increased distance walked in the incremental shuttle walk test [28 ± 44 m ( P = 0.01) and 32 ± 45 m ( P = 0.01), respectively]. In nondialysis CKD, the addition of resistance exercise to aerobic exercise confers greater increases in muscle mass and strength than aerobic exercise alone.
- Ultrasound assessment of muscle mass in response to exercise training in chronic kidney disease: a comparison with MRIPublication . Gould, Douglas W.; Watson, Emma L.; Wilkinson, Thomas J.; Wormleighton, Joanne; Xenophontos, Soteris; Viana, Joao L.; Smith, Alice C.Chronic kidney disease (CKD) is a catabolic condition associated with muscle wasting and dysfunction, which associates with morbidity and mortality. There is a need for simple techniques capable of monitoring changes in muscle size with disease progression and in response to interventions aiming to increase muscle mass and function. Ultrasound is one such technique; however, it is unknown how well changes in muscle cross-sectional area (CSA) measured using ultrasound relate to changes in whole muscle volume measured using magnetic resonance imaging. We tested whether rectus femoris CSA (RF-CSA) could be used as a valid indication of changes in quadriceps muscle volume as a single measure of muscle size and following a 12 week exercise intervention that resulted in muscle hypertrophy.