Kassia S. Beetham

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.

12 min/week of high-intensity interval training reduces aortic reservoir pressure in individuals with metabolic syndrome: a randomized trial.

Objective: Decreased aortic reservoir function leads to a rise in aortic reservoir pressure that is an independent predictor of cardiovascular events. Although there is evidence that high-intensity interval training (HIIT) would be useful to improve aortic reservoir pressure, the optimal dose of high-intensity exercise to improve aortic reservoir function has yet to be investigated. Therefore, this study compared the effect of different volumes of HIIT and moderate-intensity continuous training (MICT) on aortic reservoir pressure in participants with the metabolic syndrome (MetS). Methods: Fifty individuals with MetS were randomized into one of the following 16-week training programs: MICT [n = 17, 30 min at 60–70% peak heart rate (HRpeak), five times/week]; 4 × 4-min high-intensity interval training (4HIIT) (n = 15, 4 × 4 min bouts at 85–95% HRpeak, interspersed with 3 min of active recovery at 50–70% HRpeak, three times/week); and 1 × 4-min high-intensity interval training (1HIIT) (n = 18, 1 × 4 min bout at 85–95% HRpeak, three times/week). Aortic reservoir pressure was calculated from radial applanation tonometry. Results: Although not statistically significant, there was a trend for a small-to-medium group × time interaction effect on aortic reservoir pressure, indicating a positive adaptation following 1HIIT compared with 4HIIT and MICT [F (2,46) = 2.9, P = 0.07, &eegr;2 = 0.06]. This is supported by our within-group analysis wherein only 1HIIT significantly decreased aortic reservoir pressure from pre to postintervention (pre–post: 1HIIT 33 ± 16 to 31 ± 13, P = 0.03; MICT 29 ± 9–28 ± 8, P = 0.78; 4HIIT 28 ± 10–30 ± 9 mmHg, P = 0.10). Conclusion: Three sessions of 4 min of high-intensity exercise per week (12 min/week) was sufficient to improve aortic reservoir pressure, and thus may be a time-efficient exercise modality for reducing cardiovascular risk in individuals with MetS.

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.

Feasibility of higher intensity exercise in patients with chronic kidney disease

BACKGROUND Higher intensity exercise is a more effective way of evoking improvements in cardiorespiratory fitness in many chronic disease populations compared to moderate intensity continuous training. The aim of this study was to investigate the feasibility of participation in higher intensity exercise in patients with chronic kidney disease (CKD). METHODS This study is an observational sub-study of the intervention arm of a randomized control trial. Forty-four participants with stage 3-4 CKD in the intervention arm were required to complete a predominantly home-based 12 month individualized exercise intervention. Physical activity levels, exercise capacity (METs) and blood biochemistry were measured at baseline and 12 months. The physical activity groups (higher intensity, moderate intensity and not meeting guidelines) were determined from the six months activity prior to the 12 month testing visit. RESULTS At 12 months, the number of patients who reported performing weekly higher intensity exercise in the previous six months of the intervention increased by 23%. Participants completing higher intensity exercise had a significantly greater exercise capacity at 12 months (11.9±3.7 METs) than participants reporting moderate intensity exercise and those not meeting guidelines (9.2±1.7, 7.6±3.2 METs). Hemoglobin levels and exercise capacity were significantly higher at baseline in patients who reported exercising at higher intensities (142.9±16.1 g/L and 9.8±4.2 METs) compared to those reporting moderate intensity exercise (129.8±12.9 g/L and 8±3.1 METs) and not meeting guidelines (127.3±12.5 g/L and 6±2 METs). CONCLUSIONS The study was successful in increasing higher intensity physical activity in a large proportion of patients with CKD.

Effects of exercise and lifestyle intervention on oxidative stress in chronic kidney disease

ABSTRACT Objectives: Determine the effects of a 12-month exercise and lifestyle intervention program on changes in plasma biomarkers of oxidative stress in pre-dialysis chronic kidney disease (CKD) patients. Methods: A total of 136 stage 3–4 CKD patients were randomized to receive standard nephrological care with (N = 72) or without (N = 64) a lifestyle and exercise intervention for 12 months. Plasma total F2-isoprostanes (IsoP), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC), anthropometric and biochemical data were collected at baseline and at 12 months. Results: There were no significant differences between groups at baseline. There were no significant differences in changes for standard care and lifestyle intervention, respectively, in IsoP (p = 0.88), GPX (p = 0.87), or TAC (p = 0.56). Patients identified as having high IsoP at baseline (>250 pg/mL) had a greater decrease in IsoP with lifestyle intervention compared to standard care; however, the difference was not statistically significant (p = 0.06). There was no difference in the change in kidney function (eGFR) between standard care and lifestyle intervention (p = 0.33). Discussion: Exercise and lifestyle modification in stage 3–4 CKD did not produce changes in systemic biomarkers of oxidative stress over a 12-month period, but patients with high IsoP may benefit most from the addition of intervention to standard care.

High-intensity interval training and cardiac autonomic control in individuals with metabolic syndrome: A randomised trial

BACKGROUND Insulin resistance has been postulated to play a central role in the co-appearance of various cardiovascular disease risk factors constituting the metabolic syndrome (MetS). There is evidence that altered cardiac autonomic function (CAF) may precede the onset of insulin resistance. Exercise training has been shown to improve CAF in different populations, yet little is known regarding the exercise dose response for CAF. The aim of this study was to investigate the impact of different volumes of high-intensity interval training (HIIT) and traditional moderate-intensity continuous training (MICT) on CAF in participants with MetS. METHODS Individuals with MetS (n=56) were randomised into the following 16-week training interventions: i) MICT (n=16, 30min at 60-70%HRpeak, 5×/week); ii) 4HIIT (n=19, 4×4min bouts at 85-95%HRpeak, interspersed with 3min of active recovery at 50-70%HRpeak, 3×/week); or iii) 1HIIT (n=21, 1×4min bout at 85-95%HRpeak, 3×/week). R-R interval recorded for 5min in a supine position at pre- and post-intervention was used to derive linear (SDNN, RMSSD, pNN50, LF, HF, LF/HF) and non-linear (SD1, SD2, Alpha1, Alpha2, SampEn) heart rate variability (HRV) indices as measures of CAF. Group×time interaction effects were examined (ANCOVA) and Eta squared (η2) interaction effect sizes calculated. RESULTS While there were no significant between-group differences in CAF indices, there were small-to-medium group×time interaction effects on SDNN [F(2,52)=0.70, p=0.50, η2=0.02], RMSSD [F(2,52)=1.35, p=0.27, η2=0.03], HF power [F(2,52)=1.27, p=0.29, η2=0.03], SD1 [F(2,52)=0.47, p=0.63, η2=0.01], and SD2 [F(2,52)=0.41, p=0.67, η2=0.01]. The following represent the relative percentage increases across these variables for 4HIIT, MICT, and 1HIIT respectively (SDNN, +30%, +17%, 9%; RMSSD, +30%, +22%, -2%; HF power, +69%, +18%, +7%; SD1, +30%, +22%,-2%; SD2, +22%, +14%, 4%). CONCLUSIONS There were no significant between-group differences for the effects of exercise dose on CAF indices, however; high-volume HIIT demonstrated the greatest magnitude of effect for improving CAF in individuals with MetS.

Association between left ventricular global longitudinal strain, health‐related quality of life and functional capacity in chronic kidney disease patients with preserved ejection fraction

Patients with chronic kidney disease (CKD) have a significant burden of dyspnoea and fatigue in spite having normal left ventricular (LV) ejection fraction (EF). Global longitudinal strain (GLS) can detect subtle changes in LV function. This study aimed to evaluate the relationship between LV function, functional capacity and quality of life (QOL) in CKD patients with preserved EF.

Effect of Exercise and Lifestyle Intervention On Oxidative Stress in Chronic Kidney Disease

021 CELL BASED THERAPY IN COMBINATION WITH SERELAXIN IS CRITICAL FOR PRESERVATION OF VASCULAR INTEGRITY VIA PROMOTION OF ANGIOGENESIS AND ANASTOMOSIS B HUUSKES1, A PINTO2, C SAMUEL3, S RICARDO1 1Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria; 2Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria; 3Department of Pharmacology, Monash University, Clayton, Victoria