Erin J. Howden

Exercise & Sports Science Australia (ESSA) position statement on exercise and chronic kidney disease

OBJECTIVES Chronic kidney disease (CKD) is prevalent, affecting 13% of adult Australians and poses increased risk for cardiovascular morbidity and mortality. This position article provides evidence-based guidelines on the role of exercise training for CKD patients and provides recommendations for prescribing and delivering exercise training. DESIGN Position stand. METHODS Synthesis of published work within the field of exercise training and chronic kidney disease. RESULTS Exercise training likely to provide benefits to CKD patients, including improvements in cardio-respiratory fitness, quality of life, sympatho-adrenal activity, muscle strength and increased energy intake and possible reduction in inflammatory biomarkers. Existing studies generally report small sample sizes, brief training periods and relatively high attrition rates. Exercise training appears to be safe for CKD patients with no deaths directly related to exercise training in over 30,000 patient-hours, although strict medical exclusion criteria in previous studies resulted in 25% of patients being excluded potentially impacting the generalisability of the findings. CONCLUSIONS Aerobic exercise at an intensity of >60% of maximum capacity is recommended to improve cardio-respiratory fitness. Few data are available on resistance training and it is unclear whether this form of training retards catabolic/inflammatory processes typical of CKD. However, it should be considered important due to its proven beneficial effects on bone density and muscle mass. Due to the high prevalence and incidence of co-morbidities in CKD patients, exercise training programs should be prescribed and delivered by individuals with appropriate qualifications and experience to recognise and accommodate co-morbidities and associated complications.

Exercise Training in Chronic Kidney Disease Patients

Chronic kidney disease (CKD) is a major public health problem that affects an estimated 1.7 million Australians. Patients with CKD commonly progress to end-stage kidney disease (ESKD) requiring dialysis and/or kidney transplantation. They are at high risk of cardiovascular disease and many die from this prior to reaching ESKD. Few therapies are available to slow CKD progression and reduce cardiovascular morbidity and mortality. The benefit of exercise training has been well demonstrated in a range of disease conditions including ESKD and was recently highlighted by a systematic review in haemodialysis patients and a recent Cochrane review of all stages of CKD. However, the effects of exercise training in patients with CKD have not been extensively investigated. Our systematic search of the literature found only ten clinical trials in this area. The aim of this review is to review these studies, and to discuss the findings, safety considerations and suggest future areas of research. Overall, the majority of the studies are small, non-randomized, non-controlled trials. They have found that exercise training can increase exercise capacity, improve muscle strength and function, decrease blood pressure, and improve inflammation and oxidative stress biomarkers. The effects of exercise training on kidney function, cardiovascular disease and quality of life are unknown. Studies are needed to answer these questions and develop evidence-based exercise training guidelines for individuals with CKD.

Effect of gravity and microgravity on intracranial pressure

Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.

Exercise training in CKD: efficacy, adherence, and safety.

BACKGROUND Exercise training increasingly is recommended as an important part of the management of cardiovascular disease. However, few studies have evaluated the effectiveness of exercise training in patients with chronic kidney disease (CKD), and those that have included very selective populations. STUDY DESIGN Analysis of secondary outcomes of a randomized controlled trial, with participants randomly assigned to either lifestyle intervention or usual care (control). SETTING & PARTICIPANTS Patients with CKD stages 3 to 4 and one or more uncontrolled cardiovascular risk factor were recruited from an outpatient clinic at a large tertiary hospital. INTERVENTION Lifestyle intervention included access to multidisciplinary care through a nurse practitioner-led CKD clinic, exercise training, and a lifestyle program. The exercise training was a 2-phased program in which participants received 8 weeks of supervised training before commencing 10 months of home-based training. OUTCOMES & MEASUREMENTS Efficacy, as assessed by metabolic equivalent tasks (METs), 6-minute walk distance, Timed Get-Up-and-Go test, grip strength, and anthropomorphic measures; adherence, as assessed by self-reported physical activity; and safety, as assessed by reported serious adverse events, were recorded. RESULTS 83 patients were randomly assigned and 72 patients completed follow-up testing (intervention, n=36; control, n=36). The intervention resulted in a significant improvement in METs (pre, 7.2±3.3; post, 9.7±3.6), 6-minute walk distance (pre, 485±110m; post, 539±82m), and body mass index (pre, 32.5±6.7kg/m(2); post, 31.9±7.3kg/m(2)). Reported physical activity levels significantly increased in the intervention group at 6 months, but decreased at 12 months. There were no serious adverse events related to the exercise training. LIMITATIONS This study was not powered to evaluate the safety of exercise training on serious adverse events. CONCLUSIONS The findings from the present study suggest that an exercise program that includes a supervised and home-based training phase is effective, adhered to, and safe in patients with CKD.

Females have a blunted cardiovascular response to one year of intensive supervised endurance training

Cross-sectional studies in athletes suggest that endurance training augments cardiovascular structure and function with apparently different phenotypes in athletic males and females. It is unclear whether the longitudinal response to endurance training leads to similar cardiovascular adaptations between sexes. We sought to determine whether males and females demonstrate similar cardiovascular adaptations to 1 yr of endurance training, matched for training volume and intensity. Twelve previously sedentary males (26 ± 7, n = 7) and females (31 ± 6, n = 5) completed 1 yr of progressive endurance training. All participants underwent a battery of tests every 3 mo to determine maximal oxygen uptake (V̇o2max) and left ventricle (LV) function and morphology (cardiac magnetic resonance imaging). Pulmonary artery catheterization was performed before and after 1 yr of training, and pressure-volume and Starling curves were constructed during decreases (lower-body negative pressure) and increases (saline infusion) in cardiac volume. Males progressively increased V̇o2max, LV mass, and mean wall thickness, before reaching a plateau from month 9 to 12 of training. In contrast, despite exactly the same training, the response in females was markedly blunted, with V̇o2max, LV mass, and mean wall thickness plateauing after only 3 mo of training. The response of LV end-diastolic volume was not influenced by sex (males +20% and females +18%). After training Starling curves were shifted upward and left, but the effect was greatest in males (interaction P = 0.06). We demonstrate for the first time clear sex differences in response to 1 yr of matched endurance training, such that the development of ventricular hypertrophy and increase in V̇o2max in females is markedly blunted compared with males.

The role of exercise training in the management of chronic kidney disease.

Purpose of reviewIn this review, we summarize recent studies of exercise interventions in chronic kidney disease (CKD), potential benefits, discuss barriers to implementation and make practical recommendations for incorporating exercise training into the care of patients with CKD. Recent findingsInterventions targeting increased fitness and physical activity are effective and may have multiple potential benefits. Recommendations regarding physical activity advice have been incorporated into the recent update of the KDIGO CKD guidelines, which suggest that patients perform 30 min of moderate intensity exercise on most days of the week. Exercise as simple, popular and inexpensive as walking appears to be associated with significant health benefits. More vigorous exercise requires increased supervision but can be safely prescribed to patients with a broad range of comorbidities and may be associated with greater gains in health. SummaryPhysical activity, cardiorespiratory fitness and muscle function are low in patients with CKD. A sedentary lifestyle has been associated with increased mortality, morbidity and the risk factors that drive progression of both kidney and cardiac disease. There is much to learn about the benefits of different modalities of exercise but the time has come to routinely prescribe exercise interventions as part of standard nephrological care.

Cardiorespiratory fitness and cardiovascular burden in chronic kidney disease

OBJECTIVES Reduced functional capacity is associated with poor prognosis. In patients with chronic kidney disease the factors that contribute to low cardiorespiratory fitness are unclear. The objective of this study was to evaluate the cardiorespiratory and cardiovascular response to exercise in chronic kidney disease patients, and secondly investigate the relationships between cardiorespiratory fitness and cardiovascular burden. DESIGN Cross-sectional analysis. METHODS Baseline demographic, anthropometric and biochemical data were examined in 136 patients with moderate chronic kidney disease (age 59.7±9.6yrs, eGFR 40±9ml/min/1.73m(2), 55% male, 39% with a history of cardiovascular disease, 38% diabetic and 17% current smokers). Cardiorespiratory fitness was measured as peak VO2, left ventricular morphology and function using echocardiography, central arterial stiffness by aortic pulse wave velocity and left ventricular afterload using augmentation index. Physical activity levels were assessed using the Active Australia questionnaire. RESULTS Peak VO2 (22.9±6.5ml/kg/min) and peak heart rate (148±22bpm) were 17% and 12% lower than the age-predicted values, respectively. The low fit group were significantly older, and were more likely to have type II diabetes, cardiovascular disease, a higher BMI and be less active than the high fit group (P<0.05). The independent predictors of peak VO2 were age, type II diabetes, hemoglobin level, physical activity, aortic pulse wave velocity, augmentation index, and global longitudinal strain. CONCLUSIONS In patients with chronic kidney disease, the peak VO2 and heart rate response is markedly impaired. Reduced cardiorespiratory fitness is independently associated with increased aortic stiffness, increased left ventricle afterload, poor left ventricle function and higher burden of cardiovascular risk.

Oxidative stress contributes to muscle atrophy in chronic kidney disease patients

Abstract Objectives Patients with chronic kidney disease have impaired muscle metabolism, resulting in muscle atrophy. Oxidative stress has previously been identified as a significant contributor to muscle atrophy in other populations, but the contribution in chronic kidney disease is unknown. The aim of this study was to investigate the association between oxidative stress, grip strength, and lean mass in patients with chronic kidney disease. Methods This is a cross-sectional study of 152 participants with stage 3 or 4 chronic kidney disease. Outcome measures include grip strength, lean mass, plasma total F2-isoprostanes, inflammation, peak oxygen uptake, and standard clinical measures. Results Thirty four (22.4%) chronic kidney disease patients had elevated oxidative stress levels (plasma F2-isoprostanes >250 pg/ml), with 82% of patients below age-predicted grip strength normative values. There was a significant negative association between plasma F2-isoprostanes and grip strength (r = −0.251) and lean mass (r = −0.243). There were no associations with inflammation markers. Multiple linear regression identified plasma F2-isoprostanes as a significant predictor of grip strength independent of other predictors: sex, diabetes status, body mass index, body fat percent, and phosphate (adjusted r2 = 69.5, P < 0.001). Discussion Plasma F2-isoprostanes were independently associated with reduced strength in chronic kidney disease patients.

Neither Hematocrit Normalization nor Exercise Training Restores Oxygen Consumption to Normal Levels in Hemodialysis Patients

Patients treated with hemodialysis develop severely reduced functional capacity, which can be partially ameliorated by correcting anemia and through exercise training. In this study, we determined perturbations of an erythroid-stimulating agent and exercise training to examine if and where limitation to oxygen transport exists in patients on hemodialysis. Twenty-seven patients on hemodialysis completed a crossover study consisting of two exercise training phases at two hematocrit (Hct) values: 30% (anemic) and 42% (physiologic; normalized by treatment with erythroid-stimulating agent). To determine primary outcome measures of peak power and oxygen consumption (VO2) and secondary measures related to components of oxygen transport and utilization, all patients underwent numerous tests at five time points: baseline, untrained at Hct of 30%, after training at Hct of 30%, untrained at Hct of 42%, and after training at Hct of 42%. Hct normalization, exercise training, or the combination thereof significantly improved peak power and VO2 relative to values in the untrained anemic phase. Hct normalization increased peak arterial oxygen and arteriovenous oxygen difference, whereas exercise training improved cardiac output, citrate synthase activity, and peak tissue diffusing capacity. However, although the increase in arterial oxygen observed in the combination phase reached a value similar to that in healthy sedentary controls, the increase in peak arteriovenous oxygen difference did not. Muscle biopsy specimens showed markedly thickened endothelium and electron-dense interstitial deposits. In conclusion, exercise and Hct normalization had positive effects but failed to normalize exercise capacity in patients on hemodialysis. This effect may be caused by abnormalities identified within skeletal muscle.

Oxidative stress is associated with decreased heart rate variability in patients with chronic kidney disease

Objectives: Elevated oxidative stress and reduced heart rate variability (HRV) is prevalent in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Previous studies have identified a positive association between elevated oxidative stress and autonomic dysfunction, however this relationship has not yet been investigated in the CKD population. Methods: Plasma was collected from 78 patients with stage 3–4 CKD (estimated glomerular filtration rate 25–60 ml/min/1.73 m2) for the assessment of oxidative stress, including plasma total F2-isoprostanes, glutathione peroxidase activity and total antioxidant capacity. Time and frequency HRV parameters were measured from a three lead electrocardiogram. Results: Participants with elevated F2-isoprostanes had reduced HRV compared to patients with normal levels of F2-isoprostanes. A number of HRV parameters were found to be inversely correlated with F2-isoprostanes in all CKD patients, including SDNN (r = −0.337; P < 0.01), VLF (r = −0.281, P = 0.01), LF (r = −0.315, P < 0.01) and total power (r = −0.288, P = 0.01). Multiple linear regression found F2-isoprostanes to be an independent predictor of SDNN (r2 = 0.287, β = −0.272, P = 0.01). Discussion: Oxidative stress is significantly and independently associated with HRV in patients with CKD. Identifying oxidative stress in the pathogenesis of autonomic dysfunction may help target therapeutic strategies.