Exercise training in kidney transplant recipients (EXTRA Trial): protocol for a randomized controlled trial

Kidney transplantation improves survival and quality of life compared with long-term dialysis, yet many kidney transplant recipients remain characterized by reduced physiological reserve, cardiometabolic vulnerability, and ongoing graft-related risk. Structured exercise is a promising non-pharmacological strategy after transplantation, but its potential immunometabolic and immunomodulatory effects and their relationship with longer-term graft-related trajectories remain insufficiently characterized. The EXercise Training in Kidney TRAnsplant Recipients Trial (EXTRA Trial) is a randomized, assessor-blinded, parallel-group controlled trial that enrolled adult kidney transplant recipients approximately 6 months after transplantation. Participants are allocated 1:1 to usual post-transplant care or a supervised, progressive, combined aerobic and resistance exercise program consisting of a 2-week familiarization period followed by 24 weeks of training. The primary outcomes are the between-group differences in change in peak oxygen uptake (VO₂peak) and handgrip strength from baseline to the end of the randomized intervention. VO₂peak serves as the principal cardiorespiratory outcome and the basis for the sample-size calculation. Major secondary outcomes include patient-reported physical functioning, habitual physical activity, health-related quality of life, body composition, renal function, blood pressure, and metabolic markers. Exploratory outcomes include rejection-free survival, graft survival, circulating inflammatory cytokines (TNF-α, IL-6, and IL-2), soluble PD-1 and PD-L1, and longer-term trajectories assessed through 24 months after transplantation. The protocol follows SPIRIT 2025 recommendations and integrates exercise physiology, transplant medicine, and immune-related phenotyping to examine whether exercise-induced improvements in physiological reserve are accompanied by measurable inflammatory, immune-checkpoint, and graft-related changes.

ClinicalTrials.gov, identifier NCT06216015.