Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits

Increasing evidence indicates that exercise has beneficial effects in adults living with chronic kidney disease (CKD) or kidney failure. Exercise-mediated improvements in inflammatory biomarkers, cardiorespiratory function, muscle and bone strength, and metabolic markers such as lipoprotein profiles and insulin resistance that can ultimately lead to improvements in physical function, physical capacity and quality of life have been reported in non-dialysis CKD, dialysis and kidney transplant populations. However, mechanisms underlying these benefits have received less attention, and available clinical evidence is often from small, shorter (typically less than 12 weeks) exercise intervention studies. Data, mainly from CKD and patients on dialysis, suggest exercise mediated shifts towards a less inflammatory monocyte and T cell profile, enhanced activity of the Nrf2 pathway and reduced monocyte infiltration into adipose tissue may underly improvements in inflammatory biomarkers. Exercise-mediated enhancements in nitric oxide release and bioavailability, reduced angiotensin II accumulation in the heart, left ventricular remodelling and reductions in myocardial fibrosis may contribute to improvements in left ventricular hypertrophy. Exercise, and in particular resistance exercise, stimulates an anabolic response with skeletal muscle in CKD, but mitochondrial mass and satellite cell activation appear unresponsive or less responsive to exercise. Exercise-mediated activation of the canonical wnt pathway may lead to bone formation in CKD and regulate abnormal bone-derived hormones by increasing klotho and reducing FGF23. Longer duration studies with larger sample sizes are needed to confirm these mechanisms for populations living with CKD, kidney failure and kidney transplant recipients to provide evidence for targeted, effective exercise interventions.</p

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients

PurposePatients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients.MethodsPatients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12–14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays.ResultsDespite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis.ConclusionSix months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this.Trial registrationISRCTN1129707, prospectively registered on 05/03/2015.</div

A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass

Cardiovascular disease is the leading cause of death for patients receiving hemodialysis. Since exercise mitigates many risk factors which drive cardiovascular disease for these patients, we assessed effects of a program of intra-dialytic cycling on left ventricular mass and other prognostically relevant measures of cardiovascular disease as evaluated by cardiac MRI (the CYCLE-HD trial). This was a prospective, open-label, single-blinded cluster-randomized controlled trial powered to detect a 15g difference in left ventricular mass measured between patients undergoing a six-month program of intra-dialytic cycling (exercise group) and patients continuing usual care (control group). Pre-specified secondary outcomes included measures of myocardial fibrosis, aortic stiffness, physical functioning, quality of life and ventricular arrhythmias. Outcomes were analyzed as intention-to-treat according to a pre-specified statistical analysis plan. Initially, 130 individuals were recruited and completed baseline assessments (65 each group). Ultimately, 101 patients completed the trial protocol (50 control group and 51 exercise group). The six-month program of intra-dialytic cycling resulted in a significant reduction in left ventricular mass between groups (-11.1g; 95% confidence interval -15.79, -6.43), which remained significant on sensitivity analysis (missing data imputed) (-9.92g; 14.68, -5.16). There were significant reductions in both native T1 mapping and aortic pulse wave velocity between groups favoring the intervention. There was no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise with no significant effect on physical function or quality of life. Thus, a six-month program of intradialytic cycling reduces left ventricular mass and is safe, deliverable and well tolerated

Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a six-month programme of cycling exercise during haemodialysis

Background: Intradialytic cycling (IDC) may provide cardiovascular benefit to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a six-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines (IL-6, IL-10, TNF-α, CRP and IL6/IL-10), and their associations with physical activity, fitness and cardiovascular outcomes. Methods: Participants were randomised to either a six-month programme of IDC (thrice weekly, moderate intensity cycling at RPE 12-14) in addition to usual care (n=46), or usual care only (control group; n=46). Outcome measures were obtained at baseline and then again at six months. Results: There was no significant (P=0.137) difference in circulating endotoxin between groups at 6-months (IDC group: 0.34±0.08 EU/mL; control group: 0.37±0.07 EU/mL). There were no significant between group difference in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP, and IL-6/IL-10. Conclusions: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation

Seroprevalence of antibody to S1 spike protein following vaccination against COVID-19 in patients receiving hemodialysis: a call to arms

Letter to the Editor