Exercise-Based Prehabilitation for Kidney Transplant Candidates: the FRAILMar Randomized Controlled Trial.
Pérez-Sáez, M. J., et al.Am J Kidney Dis. 2025 Nov;86(5):634-645.e1.
Aims
The authors aim to evaluate whether an 8-week, exercise-based prehabilitation program improves exercise capacity, muscle function, and muscle size in prospective kidney transplant recipients.
Interventions
Multimodal, exercise-based prehabilitation: three 1-hour sessions/week for 8 weeks (aerobic cycling at ~60% peak workload with progression, resistance training for upper/lower limbs, inspiratory muscle training), delivered as supervised in-person or video-supervised sessions plus one independent home session weekly; protein supplementation after sessions. Controls received standard care with WHO-aligned activity advice. During the 8-week program, candidates were suspended from the waitlist and reinstated after post-intervention testing.
Participants
121 prospective adult kidney transplant recipients on the deceased-donor waiting list, randomised 1:1 and stratified by frailty. Exclusions were minimal (inability to participate or specific muscle disease/injury). 106 completed the 8-week intervention. (mean age 63, 76% men); randomised 1:1 and stratified by frailty (Fried phenotype ≥2 = frail; 40% frail). Single-centre RCT (Barcelona).
Outcomes
Primary outcome was change in maximal workload (Wmax) on cardiopulmonary exercise testing (CPET). Secondary outcomes included: VO₂peak/METs/ventilatory thresholds, 6-minute walk distance, gait speed, handgrip strength, quadriceps strength, inspiratory/expiratory pressures, ultrasound muscle thickness (rectus femoris, forearm), frailty status (Fried, Clinical Frailty Scale).
Follow-up
9–12 weeks (post-intervention), and again at 6 months.
CET Conclusions
The authors present a pre-specified interim analysis from moderately sized single-centre RCT for an 8-week prehabilitation program (aerobic cycling at 60% peak workload with progression, resistance work, inspiratory muscle training) versus standard care. They found the program improves exercise capacity, grip strength, inspiratory muscle strength, and thigh muscle thickness in kidney transplant candidates, including the frail subgroup, with no excess harms and good adherence among completers. They found their intervention to significantly increase Wmax (+12.8 watts vs control, 95% CI 3.4–22.2; p=0.008), hand grip (+1.8 kg, 0.7–2.8; p<0.001), rectus femoris thickness (+1.2 mm, 0.3–2.0; p=0.007), but METs, gait speed, inspiratory muscle strength (PImax) also improved; VO₂peak and 6MWD did not differ significantly. However, this is a preliminary analysis limited to functional/physiologic endpoints before transplantation, with short follow-up and multiple comparisons. Key post-transplant clinical outcomes (LOS, complications, graft/patient survival) are still pending and are ultimately the relevant endpoints. The study is of reasonable quality, but allocation concealment/blinding were not feasible, and selection and informative dropout biases are possible. Their findings are in keeping with other similar studies of prehabilitation programs of this nature demonstrating functional gains in transplant recipients, if in the final analysis this confers benefit with the clinical outcomes, it would support pre-listing or “on-hold” prehabilitation windows with hybrid supervision as a standard-of-care adjunct to improve outcomes, especially in those frailer patients. Until the overall outcome data is published it should not inform clinical practice, centres could consider structured prehabilitation pathways to enhance pre-op fitness in a sub-set of frail or deconditioned patients.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT04701398