ECSS Paris 2023: OP-MH23
INTRODUCTION: Acute rejection and long-term graft dysfunction remain major barriers to optimal outcomes after kidney transplantation. While exercise is recognized for its cardiometabolic benefits, its potential role in modulating alloimmune responses has not been established. The EXTRA trial was designed to evaluate whether structured exercise training influences rejection risk, body composition, and immune checkpoint regulation in kidney transplant recipients. METHODS: The EXTRA trial is a randomized controlled clinical trial including 200 adult kidney transplant recipients allocated to structured exercise training (n=88) or usual care (n=112) and followed for 24 months. The intervention consisted of supervised, combined aerobic and resistance training. The primary outcome was biopsy-proven acute rejection. Secondary outcomes included body composition, circulating immune checkpoint markers (PD-1/PD-L1 expression in peripheral immune cells), inflammatory mediators, and uremic profile. Analyses were performed using Kaplan-Meier survival curve followed by Cox regression and mixed-effects models adjusted for relevant clinical covariates. RESULTS: Over 24 months, the exercise group exhibited a significantly lower incidence of acute rejection compared to usual care (p<0.05). Exercise training resulted in increased lean mass and reduced fat mass compared with controls (p<0.001). Mechanistically, the intervention group demonstrated modulation of immune checkpoint expression, characterized by a more regulated PD-1/PD-L1 profile and reduced pro-inflammatory cytokine levels. In addition, exercise improved the uremic profile. These findings remained significant after multivariable adjustment. CONCLUSION: In this randomized controlled trial, structured exercise training reduced rejection incidence and promoted favorable immunometabolic adaptations in kidney transplant recipients. These findings suggest that exercise may act as a non-pharmacological immunomodulatory strategy capable of influencing alloimmune regulation and graft outcomes. Exercise prescription should be considered as an adjunct component of post-transplant care. Importantly, the reduction in rejection risk was consistent across subgroups stratified by age, sex, baseline renal function, and immunosuppressive regimen, suggesting a robust intervention effect. No adverse events related to exercise were observed, reinforcing its safety in this high-risk population. To our knowledge, this is one of the first randomized controlled trials to demonstrate that exercise training can modulate immune checkpoint pathways in transplant recipients. These findings provide novel insight into the interaction between physical exercise and alloimmune regulation, supporting the integration of structured exercise programs into standard post-transplant management strategies.
Read CV Hugo CorrêaECSS Paris 2023: OP-MH23
INTRODUCTION: Age-related declines in cardiorespiratory fitness are a key physiological hallmark of aging and are closely associated with reduced physical function and quality of life in older adults. Exercise training is widely recommended to promote healthy aging; however, its role in intervening in age-related physiological decline and the underlying mechanisms remain insufficiently understood. Peak oxygen uptake (VO2peak) is a central indicator of cardiorespiratory fitness and a potential mechanistic link between exercise training and functional health outcomes. This study examined whether improvements in VO2peak mediate the effects of exercise training on physical quality of life in older adults, providing longitudinal mechanistic evidence for exercise as an intervention targeting age-related functional decline. METHODS: Forty community-dwelling older adults were allocated to an exercise training group (n = 20) or a control group (n = 20). The exercise group completed 3 months of supervised combined aerobic and resistance training, while the control group maintained their usual lifestyle. VO2peak and health-related quality of life were assessed before and after the intervention, with the Physical Component Summary (PCS) score derived from the SF-36 questionnaire. Linear mixed-effects models were used to examine group-by-time interaction effects, with intervention effects evaluated after adjusting for age, sex, body mass index (BMI), and other relevant covariates. Pearson correlation analysis and causal mediation analysis based on changes (Delta) in VO2peak and PCS were subsequently conducted. Nonparametric bootstrap procedures with 5000 resamples were applied to estimate mediation effects and corresponding confidence intervals. RESULTS: Significant group-by-time interactions were found for VO2peak and PCS (p < 0.01), with greater improvements in the exercise group. Delta VO2peak was positively correlated with Delta PCS (r = 0.69, p < 0.001). Mediation analysis indicated that Delta VO2peak significantly mediated the effect of exercise on PCS (ACME = 2.92, 95% CI: 0.81-5.43, p = 0.008), accounting for approximately 39% of the total effect (total effect = 7.49, p < 0.001). The direct effect of exercise remained significant (ADE = 4.56, p = 0.004). CONCLUSION: Using a controlled longitudinal design, this study provides mechanistic evidence that exercise training can intervene in age-related functional decline by improving VO2peak, which in turn contributes to better physical quality of life in older adults. Beyond enhancing cardiorespiratory fitness levels, the findings suggest that structured exercise training may modify the age-related trajectory of cardiorespiratory fitness decline. VO2peak therefore represents not only a key outcome of exercise training, but also a modifiable physiological pathway through which exercise may influence functional aging.
Read CV Kexin DingECSS Paris 2023: OP-MH23
INTRODUCTION: Sleep disturbances are common among individuals with chronic primary low back pain (CPLBP), with 59% of them experiencing poor sleep quality (1). This study aimed to study the sequential effects of a two-phase multimodal intervention compared with a control group on sleep quality in individuals with CPLBP within the HEALTHYBACK randomized controlled trial (2). METHODS: Seventy participants with CPLBP were randomized; per-prtocol analysis included individuals attendeding ≥65% of sessiones (mean age 51.1 ± 10.8 years; 39 women): control group (CG, n=33), and multimodal intervention group (MG, n=23). The IG completed a 16-week two-phase intervention conducted in hospital setting. Phase I (8-week) comprosed supervised physical exercise (2 sessions/week, 45 min), mindfulness-based stress reduction (1 session/week, 2.5 h), pain neuroscience education (biweekly, 2.5 h) and daily behaviour change supported by a wrist-worn activity prompting device. Phase II (8 weeks) consisted of supervised functional full-body muscle strengthening exercise (3 sessions/week, 45 min). The CG maintained usual lifestyle habits. Sleep quality (0-21, higher scores represent poorer sleep quality) was assessed using the Pittsburgh Sleep Quality Index at baseline, after Phase I, and after Phase II. Within-group changes were examined using repeated-measures ANOVA. Between-group differences in change scores (post–pre and post2–pre) were analyzed using ANCOVA adjusted for baseline values. RESULTS: Within-group analyses showed significant improvements in sleep quality after Phase I (mean difference = −1.96; 95% CI −3.33 to −0.59, p=0.070) and demonstrated greater improvements following Phase II (−2.61; 95% CI −4.16 to −1.06, p=0.020) in the IG. No significant changes were observed in the CG across time points. Between-group analyses (ANCOVA on change scores) revealed significantly greater reductions in sleep quality in the IG compared with the CG after Phase I (adjusted mean difference in change = −1.90; 95% CI −3.65 to −0.15; p=0.034) and after Phase II (−1.76; 95% CI −3.37 to −0.15; p=0.033). CONCLUSION: A structured two-phase multimodal intervention, followed by moderate-to-high intensity functional full-body muscle strengthening exercise, significantly improved subjective sleep quality in individuals with CPLBP compared with usual care. These findings support the potential role of multidimensional exercise-based approaches in addressing sleep disturbances in this population. Future studies incorporating objective sleep assessments (e.g., actigraphy or polysomnography) are warranted to complement these results. REFERENCES: (1) Alsaadi SM, et al. Eur Spine J (2011) 20:737–743. doi 10.1007/s00586-010-1661-x (2) Tsiarleston G, et al. BMJ Open Sp Ex Med 2024;10:e002188. doi:10.1136/bmjsem-2024-002188 FUNDING: Instituto de Salud Carlos III (CP20/00178 and PI22/01791).
Read CV MILKANA MARIA BORGES COSICECSS Paris 2023: OP-MH23