Van obstakels naar opportuniteiten: fysieke fitheid en fysieke activiteit na niertransplantatie

Kidney transplantation is a lifesaving intervention, improving quality and quantity of life compared to dialysis. Nevertheless, kidney transplant recipients (KTRs) still face a two- to seven-fold higher mortality risk than the general population, with cardiovascular disease as the leading cause of death in recipients with a functioning graft. Among modifiable risk factors, reduced physical fitness and low physical activity play a pivotal role in driving cardiovascular morbidity and mortality. International guidelines therefore recommend integrating assessment and promotion of fitness and activity into routine post-transplant care. However, adoption in clinical practice remains limited, and important knowledge gaps persist. This doctoral thesis aimed to address these gaps by improving assessment, understanding, and therapeutic application of physical fitness and activity in de novo KTRs. The first part of this doctoral thesis focused on improving the assessment of cardiorespiratory fitness (CRF) and physical activity in post-transplant practice. While cardiopulmonary exercise testing (CPET; VO₂peak) is the gold standard assessment for CRF, its clinical use is limited by practical constraints. Therefore, Chapter 1 evaluated whether the 6 min walk test (6MWT) could serve as a viable alternative for CPET in 85 KTRs three months post-transplant. Although the 6MWT showed moderate-to-strong correlations with VO₂peak, agreement between two methods was poor, with systematic overestimation of CRF by the 6MWT. Moreover, CPET identified cardiovascular abnormalities and underlying mechanisms of exercise intolerance, highlighting its superior clinical utility for safe and precise exercise prescription in KTRs. In line, Chapter 2 examined whether the brief self-reported Physical Activity Vital Sign (PAVS) questionnaire could be used to accurately reflect objectively measured physical activity early after kidney transplantation. In 60 KTRs at three months post-transplant, PAVS results were found to require cautious interpretation: while active patients tended to underestimate, inactive patients tended to overestimate actual physical activity, with the PAVS missing up to one-third of KTRs who would benefit from physical activity interventions. Therefore, accelerometery remains the preferred method for early post-transplant activity assessment. The second part of this doctoral thesis focused on increased understanding of post-transplant physical fitness and activity behaviour. Chapter 3 showed, by means of a review of the literature, that CRF progressively declines with advancing CKD and only partially recovers after transplantation, with VO₂peak remaining approximately 30% below predicted norms within the first year post-transplant. In line, Chapter 5 showed that, in 60 KTRs three months post-transplant, CRF was markedly reduced (68±15% of predicted) and emerged as the sole fitness component being independently associated with physical activity. Low CRF increases the relative effort of everyday activities, making even moderate-intensity tasks like walking, carrying groceries, or cycling exhausting. Consequently, generic advice to "be more active" is unlikely to translate into meaningful behaviour change when underlying CRF is inadequate. Therefore, early rehabilitation should prioritize structured exercise to restore CRF. Nevertheless, CRF represents only one aspect influencing physical activity. The systematic review in Chapter 4 highlighted a wide range of barriers to post-transplant physical activity across physical, psychological, social, and environmental domains. Based on these barriers and motivators, behavioural change techniques were selected to overcome them, including goal-setting, self-monitoring, autonomy-supportive planning, social support, education, and environmental facilitation. Following the initial exercise program, interventions should shift toward promoting long-term physical activity through behaviour change strategies. Finally, the last part of this doctoral thesis explored the therapeutic potential of physical activity. While evidence demonstrates that physical activity interventions improve CRF, physical activity levels, muscle strength, QoL, and markers of cardiovascular health in KTRs, important knowledge gaps remain. Due to high heterogeneity in the current evidence, exercise prescriptions remain vague, with no evidence on optimal training intensity. In addition, the effect of physical activity on novel targets such as the gut microbiome are underexplored despite its prognostic relevance in KTRs. In Chapter 6 underlying mechanisms through which physical activity could positively modulate the gut microbiome in CKD, are reviewed. In Chapter 7 the PHOENIX-Kidney study is presented, a randomized controlled trial that evaluates the efficacy of a home-based exercise and physical activity intervention in de novo KTRs. PHOENIX-Kidney (currently ongoing) is not only addressing the optimal training intensity in KTRs and evaluating the effect of physical activity on the gut microbiome in KTRs, it also integrates theory-based approach to physical activity, incorporating key behaviour change techniques identified in Chapter 4.