A Pilot Randomised Controlled Trial of the Effects of a Structured, Home-based Exercise Program on Cardiovascular StructurE and Function in Renal Transplant Recipients: The ECSERT Study

Kidney transplantation confers a significant survival advantage over remaining on dialysis, but CVD remains the leading cause of death for RTRs and of graft loss. Acute myocardial infarction accounts for 15-20% of CVD-related deaths in RTRs, but sudden cardiac death, or death from fatal arrhythmia account for at least double this number, suggesting classical atheromatous coronary artery disease driven by traditional cardiometabolic risk factors, is not the dominant driving force of CVD in RTRs. Non-traditional cardiometabolic risk factors including endothelial dysfunction, systemic inflammation, acute rejection, anaemia and deranged bone-mineral metabolism are of at least equal importance in the pathogenesis of CVD in RTRs and drive pathological changes in cardiovascular structure and function that associate strongly with mortality. This is further illustrated by the fact that traditional CVD risk-stratification tools dramatically underestimate cardiovascular risk in patients with CKD, coronary revascularization does not improve outcomes for RTRs as it does in the general population and cardiac events are more likely to be fatal in RTRs than the general population. Immunosuppressive agents are well known to drive traditional CVD risk factors, but also drive non-traditional cardiometabolic risk factors. Cost-effective, deliverable interventions are needed to address the burden of CVD in RTRs by targeting traditional and non-traditional risk factors. Supervised exercise interventions in RTRs improve cardiorespiratory fitness and a variety of traditional and non-traditional risk factors for CVD, including metabolic profile, vascular stiffening, central adiposity and inflammatory cell and cytokine profiles, but are not realistically deliverable in the current financial climate. Home-based exercise training programs have been shown to be deliverable in patients on dialysis and patients undergoing cardiac rehabilitation, but the effectiveness and deliverability of home-based exercise interventions are largely untested in RTRs. It cannot be assumed such programs will be acceptable to RTRs, whose home-lives, social and occupational circumstances are significantly different to dialysis and cardiac patients. Many RTRs have had enforced sedentary lifestyles prior to transplantation as dialysis patients and their goals for rehabilitation as well as the disease processes at work are different to both dialysis and cardiac patients.

There are limited data on whether exercise-induced improvements in cardiometabolic risk translate into improvements in cardiovascular structure and function in RTRs. CMR is able to measure multiple clinically pertinent aspects of CVD processes in RTRs that relate closely to outcome with great accuracy, including:

• left ventricular hypertrophy
• myocardial fibrosis
• aortic stiffness
• coronary artery function
• myocardial steatosis
• subclinical systolic and diastolic dysfunction

This pilot randomised clinical trial will assess the deliverability of a combined aerobic and resistance, home-based, exercise intervention in RTRs. It will define recruitment and dropout rates from this newly designed, home-based, intervention and baseline values for CMR measures that assess prognostically important aspects of CVD in RTRs for the first time. Furthermore, it will test the effects of the intervention on traditional and novel CMR outcome measures that assess prognostically important aspects of CVD that relate directly to cardiovascular outcomes for the first time, providing estimates of effect-sizes on outcome measures. These data will be used to inform the design of a future, definitive study. This study will further the investigator's ability to make objective measures of cardiovascular health in RTRs, with the opportunity to compare CMR measures with traditional measures of cardiovascular fitness. The qualitative component of this study will refine the exercise intervention to maximize uptake in future studies and adoption into clinical practice.