João L. Viana

Physical Exercise in Patients with Severe Kidney Disease

Patients with advanced chronic kidney disease (CKD), especially those on long-term dialysis, often suffer from muscle wasting and excessive fatigue. It is known that inactivity, muscle wasting and reduced physical functioning are associated with increased mortality in CKD. Known causes include uraemic myopathy and neuropathy, inactivity, and anaemia. Exercise in patients receiving regular dialysis treatment for end-stage renal disease was first introduced 3 decades ago, but is still only offered in a minority of renal units around the world, despite a significant body of evidence to support its use. Work is needed to increase awareness of the potential benefits of increased physical activity for patients with advanced CKD. This review summarizes the mechanisms of exercise intolerance and debility in advanced CKD patients, the methods used for the estimation of functional capacity, the options currently available for exercise training, and their influence on the well-being of this group of patients.

The effect of physical activity on mediators of inflammation.

Being physically active and undertaking exercise on a regular basis are critical lifestyle behaviours which protect against the development of numerous chronic metabolic conditions. One of the key mechanisms by which physical activity exerts favourable health effects appears to be due to its capacity to reduce chronic low‐grade inflammation. Single bouts of exercise have a potent anti‐inflammatory influence with recent advances describing important effects of acute exercise on inflammatory mediators produced within skeletal muscle (myokines), adipose tissue (adipokines) and leucocytes. The accumulated effects of physical activity or exercise training on systemic inflammation have been studied widely within epidemiological research; however, information from intervention trials is still emerging. Current data suggest that the most marked improvements in the inflammatory profile are conferred with exercise performed at higher intensities, with combined aerobic and resistance exercise training potentially providing the greatest benefit. The purpose of this review is to describe recent advances in our understanding surrounding the acute and chronic effects of physical activity on key mediators of inflammation. Within this, particular attention is given to the interleukin‐6 system owing to its apparent centrality in mediating the anti‐inflammatory effects of exercise.

Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women.

This study compared the effects of a resistance training protocol and a moderate-impact aerobic training protocol on bone mineral density (BMD), physical ability, serum osteoprotegerin (OPG), and receptor activator of nuclear factor kappa B ligand (RANKL) levels. Seventy-one older women were randomly assigned to resistance exercise (RE), aerobic exercise (AE) or a control group (CON). Both interventions were conducted 3 times per week for 8 months. Outcome measures included proximal femur BMD, muscle strength, balance, body composition, serum OPG, and RANKL levels. Potential confounding variables included dietary intake, accelerometer-based physical activity (PA), and molecularly defined lactase nonpersistence. After 8 months, only RE group exhibited increases in BMD at the trochanter (2.9%) and total hip (1.5%), and improved body composition. Both RE and AE groups improved balance. No significant changes were observed in OPG and RANKL levels, and OPG/RANKL ratio. Lactase nonpersistence was not associated with BMD changes. No group differences were observed in baseline values or change in dietary intakes and daily PA. Data suggest that 8 months of RE may be more effective than AE for inducing favourable changes in BMD and muscle strength, whilst both interventions demonstrate to protect against the functional balance control that is strongly related to fall risk.

Exercise Training Improves Diastolic Function in Heart Failure Patients

PURPOSE The studys purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved, mild, and moderate to severe reduction of left ventricular ejection fraction (LVEF). METHODS Ninety-eight patients with moderate to severe (n = 34), mild (n = 33), and preserved (n = 31) LVEF were randomly assigned to exercise training plus usual care (n = 65) or usual care alone (n = 33) in a randomization ratio of 2:1. Left ventricular function, left ventricular dimensions, and exercise tolerance were assessed before and after each intervention. RESULTS Exercise tolerance and LVEF increased with exercise training in all patient groups, whereas they remained unchanged after usual care alone. Exercise training increased the mean ratio of early to late mitral inflow velocities (E/A ratio) and decreased deceleration time (DT) of early filling in patients with mild and preserved LVEF. In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction (DT < 160 ms), exercise training decreased E/A ratio and increased DT, both of which were unchanged after usual care alone. In the remaining patients (DT > 160 ms), exercise training also improved mitral inflow patterns. Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF. CONCLUSIONS These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction.

Evidence for Anti-Inflammatory Effects of Exercise in CKD

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.

Benefits of regular walking exercise in advanced pre-dialysis chronic kidney disease

BACKGROUND There is increasing evidence of the benefit of regular physical exercise in a number of long-term conditions including chronic kidney disease (CKD). In CKD, this evidence has mostly come from studies in end stage patients receiving regular dialysis. There is little evidence in pre-dialysis patients with CKD Stages 4 and 5. METHODS A prospective study compared the benefits of 6 months regular walking in 40 pre-dialysis patients with CKD Stages 4 and 5. Twenty of them were the exercising group and were compared to 20 patients who were continuing with usual physical activity. In addition, the 40 patients were randomized to receive additional oral sodium bicarbonate (target venous bicarbonate 29 mmol/L) or continue with previous sodium bicarbonate treatment (target 24 mmol/L). RESULTS Improvements noted after 1 month were sustained to 6 months in the 18 of 20 who completed the exercise study. These included improvements in exercise tolerance (reduced exertion to achieve the same activity), weight loss, improved cardiovascular reactivity, avoiding an increase in blood pressure medication and improvements in quality of health and life and uraemic symptom scores assessed by questionnaire. Sodium bicarbonate supplementation did not produce any significant alterations. CONCLUSIONS This study provides further support for the broad benefits of aerobic physical exercise in CKD. More studies are needed to understand the mechanisms of these benefits, to study whether resistance exercise will add to the benefit and to evaluate strategies to promote sustained lifestyle changes, that could ensure continued increase in habitual daily physical activity levels.

Progressive Resistance Exercise Training in CKD: A Feasibility Study

BACKGROUND 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. STUDY DESIGN Parallel randomized controlled feasibility study. SETTING & PARTICIPANTS Patients with CKD stages 3b to 4 were randomly assigned to the exercise (n=20; 11 men; median age, 63 [IQR, 57-65] years; median estimated glomerular filtration rate, 28.5 [IQR, 19.0-32.0] mL/min/1.73 m(2)) or nonexercise control (n=18; 14 men; median age, 66 [IQR, 45-79] years; estimated glomerular filtration rate, 20.5 [IQR, 16.0-26.0] mL/min/1.73 m(2)) group. INTERVENTION Patients in the exercise group undertook an 8-week progressive resistance exercise program consisting of 3 sets of 10 to 12 leg extensions at 70% of estimated 1-repetition maximum thrice weekly. Patients in the control group continued with usual physical activity. OUTCOMES Primary outcomes were related to study feasibility: eligibility, recruitment, retention, and adherence rates. Secondary outcomes were muscle anatomical cross-sectional area, muscle volume, pennation angle, knee extensor strength, and exercise capacity. MEASUREMENTS Two- and 3-dimensional ultrasonography of skeletal muscle, dynamometry, and shuttle walk tests at baseline and 8 weeks. RESULTS Of 2,349 patients screened, 403 were identified as eligible and 38 enrolled in the study. 33 (87%) completed the study, and those in the exercise group attended 92% of training sessions. No changes were seen in controls for any parameter. Progressive resistance exercise increased muscle anatomical cross-sectional area, muscle volume, knee extensor strength, and exercise capacity. LIMITATIONS No blinded assessors, magnetic resonance imaging not used to assess muscle mass, lack of a healthy control group. CONCLUSIONS This type of exercise is well tolerated by patients with CKD and confers important clinical benefits; however, low recruitment rates suggest that a supervised outpatient-based program is not the most practical implementation strategy.

Physiological benefits of exercise in pre-dialysis chronic kidney disease

Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and muscle wasting, arising from numerous factors associated with declining renal function and lifestyle factors. Exercise has the ability to impact beneficially on the comorbidities associated with CKD and is accepted as an important intervention in the treatment, prevention and rehabilitation of other chronic diseases, however, the role of exercise in CKD is overlooked, with the provision of rehabilitation programmes well behind those of cardiology and respiratory services. Whilst there is now a large evidence base demonstrating the efficacy and safety of exercise training interventions in patients receiving dialysis, and this is now becoming incorporated into clinical guidelines for treatment of dialysis patients, there is a paucity of research evaluating the effectiveness of exercise in patients with CKD who are not on dialysis. Despite this, existing studies indicate that exercise can improve physical functioning and impact positively on the mediators of co‐morbid diseases and upstream factors associated with progression of renal disease. Although preliminary evidence appears positive, more research is required to identify the best modes, frequency and intensities of exercise in order to optimise exercise prescription in pre‐dialysis CKD patients. This review summarizes what is known about the main effects of exercise in pre‐dialysis CKD patients, discusses the potential of exercise in the rehabilitation and treatment of disease and highlights the need for further research.

Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women.

This study examines the effects of 32 weeks of exercise training on balance, lower-extremity muscle strength, bone mineral density (BMD) and serum levels of bone metabolism and inflammatory markers in older adults. Forty-seven healthy older adults (women=24, men=23; mean age 68.2 years) participated in a exercise intervention (60min/session) that included resistance exercise training (2 days/week) at 75-80% of maximum plus a multicomponent weight-bearing impact exercise training (1 day/week). Outcome measures included lumbar spine and proximal femoral BMD, dynamic balance, muscle strength, serum levels of bone metabolism markers [osteocalcin (OC), C-terminal telopeptide of Type I collagen (CTX), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL)] and serum levels of inflammatory markers [high sensitive (hs)-C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ]. Potential confounding variables included body composition, dietary intake (using 4-day diet records), and accelerometer-based physical activity. After 32 weeks, both men and women increased dynamic balance (6.4%), muscle strength (11.0%) and trochanter (0.7%), intertrochanter (0.7%), total hip (0.6%), and lumbar spine BMD (1.7%), while OC, CTX, OPG and RANKL levels remained unchanged. In addition, hs-CRP and IFN-γ levels were decreased, while TNF-α levels were unchanged, and a decrease in IL-6 levels was only observed in men. These findings suggest that our combined impact protocol reduces inflammation and increases BMD, balance, and lower-extremity muscle strength, despite having little effect on bone metabolism markers. This reinforces the role of exercise to counteract the age-related inflammation, and the muscle strength, balance and BMD reduction.

Physical activity in primary and secondary prevention of cardiovascular disease: Overview updated.

Although the observed progress in the cardiovascular disease treatment, the incidence of new and recurrent coronary artery disease remains elevated and constitutes the leading cause of death in the developed countries. Three-quarters of deaths due to cardiovascular diseases could be prevented with adequate changes in lifestyle, including increased daily physical activity. New evidence confirms that there is an inverse dose-response relationship between physical activity and cardiovascular disease and mortality risk. However, participation in moderate to vigorous physical activity may not fully attenuate the independent effect of sedentary activities on increased risk for cardiovascular diseases. Physical activity also plays an important role in secondary prevention of cardiovascular diseases by reducing the impact of the disease, slowing its progress and preventing recurrence. Nonetheless, most of eligible cardiovascular patients still do not benefit from secondary prevention/cardiac rehabilitation programs. The present review draws attention to the importance of physical activity in the primary and secondary prevention of cardiovascular diseases. It also addresses the mechanisms by which physical activity and regular exercise can improve cardiovascular health and reduce the burden of the disease.