Effect of lifestyle intervention on systemic oxidative stress in kidney transplant recipients: A post-hoc analysis of the Active Care after Transplantation (ACT) randomized controlled trial

Background: Oxidative stress is associated with adverse outcomes in kidney transplant recipients (KTR), including graft failure, morbidity, and mortality. Since both exercise training and dietary modifications have the potential to improve redox status, we aimed to investigate the potential mitigating effects of exercise or exercise plus diet intervention on circulating levels of free thiols (R-SH) as marker of systemic redox status in KTR. Methods: We conducted a post-hoc analysis of the Active Care after Transplantation (ACT) study, a randomized controlled lifestyle intervention trial which proved to enhance physical functioning of KTR. Systemic R-SH levels were quantified at baseline, 3-months, and 15-months (end of study) using a colorimetric detection method. Estimated marginal means (EMM) were reported using general linear mixed models. Results: KTR were randomized to usual care (n = 40), exercise intervention (n = 54), or exercise plus diet intervention (n = 55). At 3 months post-baseline, systemic R-SH concentrations decreased significantly in the control group, while the intervention groups showed a less pronounced decrease, although the difference compared to control nearly reached statistical significance in either the exercise intervention group (EMM +20.2 μM (95%CI -1.4, +41.9), P = 0.067) or the exercise plus diet intervention group (EMM +18.9 μM (95%CI -2.7, +40.4), P = 0.086). At 15 months post-baseline, R-SH concentrations further decreased in the exercise intervention group, resulting in a difference compared to control of +9.0 μM (95%CI -14.4, +32.3; P = 0.45), whereas R-SH concentrations increased to above baseline in the exercise plus diet intervention group, with a statistically significant difference compared to control of +32.8 μM (95%CI +9.4, +56.2; P = 0.006). Conclusions: Lifestyle changes involving exercise and diet positively impacted systemic R-SH, suggesting that reducing oxidative stress through lifestyle interventions could potentially contribute to clinical benefits in KTR.