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Exercise for Solid Organ Transplant Candidates and Recipients

A Joint Position Statement of the Canadian Society of Transplantation and CAN-RESTORE

Janaudis-Ferreira, Tania PhD1,2,3,4; Mathur, Sunita PhD4,5; Deliva, Robin MSc5,6,7; Howes, Nancy MSc8; Patterson, Catherine MSc5,6,7; Räkel, Agnès MD9,4; So, Stephanie MSc5,6,7; Wickerson, Lisa PhD10; White, Michel MD11; Avitzur, Yaron MD12; Johnston, Olwyn MSc, MD13; Heywood, Norine RN14; Singh, Sunita MSc, MD15; Holdsworth, Sandra4

doi: 10.1097/TP.0000000000002806
In View: Special Article
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Background. The objectives of this position statement were to provide evidence-based and expert-informed recommendations for exercise training in adult and children solid organ transplant (SOT) candidates and recipients and on the outcomes relevant to exercise training and physical function that should be evaluated in SOT.

Methods. We identified randomized controlled trials (RCTs) and systematic reviews of exercise interventions in adult and pediatric SOT candidates and recipients. When RCTs were not available, studies of any design were reviewed. The key recommendations were based on scientific evidence and expert-informed opinion.

Results. We recommended that exercise training should be offered in the pre- and posttransplant phase for both adults and children. In adults, exercise training pretransplant was safe, but there was insufficient evidence to provide specific guidelines on the training characteristics. RCTs in adult SOT recipients demonstrated that exercise training improved exercise capacity, lower extremity muscle strength, and health-related quality of life. To obtain benefits, exercise training should be of moderate to vigorous-intensity level, 3–5 times a week for a minimum of 8 weeks. In pediatrics, there is an urgent need for high-quality multicenter clinical trials in the pre- and posttransplant phases. Due to limited evidence, specific recommendations regarding training characteristics could not be provided for pediatrics.

Conclusions. The clinical relevance of this position statement is that it provides a key step toward raising awareness of the importance of exercise training in SOT patients among transplant professionals. It also identifies key areas for further research.

1 School of Physical and Occupational Therapy, McGill University, Montreal, QC, Canada.

2 Translational Research in Respiratory Diseases program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

3 Respiratory Epidemiology and Clinical Research Unit, Research Institute, McGill University Health Center, Montreal, QC, Canada.

4 Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada.

5 Department of Physical Therapy, University of Toronto, Toronto, ON, Canada.

6 Rehabilitation Services, The Hospital for Sick Children, Toronto, ON, Canada.

7 Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Canada.

8 Department of Physical Therapy, London Health Sciences Centre, London, ON, Canada.

9 Division of Endocrinology, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada.

10 Toronto Lung Transplant Program, University Health Network, Toronto, ON, Canada.

11 Department of Medicine, University of Montreal, Montreal, QC, Canada.

12 Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.

13 Kidney and Pancreas Transplant Program, Vancouver General Hospital, Vancouver, BC, Canada.

14 Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada.

15 Kidney Transplant Program, University Health Network, Toronto, ON, Canada.

Received 7 May 2019. Revision received 13 May 2019.

Accepted 13 May 2019.

T.J-F. and S.M. are co-first authors.

T.J-F. and S.M. are the co-chairs of the working group who developed this position statement. They designed the outline of the manuscript, conducted literature review, retrieved data, and wrote most of the sections. R.D., N.Howes, C.P., A.R., S.So, L.W., and M.W. are members of the working group. They provided feedback on the outline of the manuscript, conducted literature review, and assisted with data retrieval and manuscript writing. Y.A., O.J., N.Heywood, and S.Singh are members of the Leading Clinical Practice Committee of the Canadian Society of Transplantation. They provided guidance on the methodology of developing a position statement and provided critical feedback on the outline and final version of the manuscript. S.H. is a patient partner. She provided critical feedback on the outline and final version of the manuscript.

TJF holds a salary award from the Fonds de Recherche Sante Quebec (FRQS). The other authors have no conflict of interested to declare related to this work.

No specific funding was received to create this work. T.J-F. holds a salary award from Fonds de Recherche Sante Quebec.

Correspondence: Tania Janaudis-Ferreira, PhD, 5252 de Maisonneuve Blvd W, room #3E.01, Montreal, Quebec, Canada, H4A 3J1. (tania.janaudis-ferreira@mcgill.ca).

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INTRODUCTION

There is a growing interest in the role of exercise and physical activity in improving health outcomes and quality of life in individuals undergoing solid organ transplantation (SOT).1 Exercise training has been shown to be beneficial across several chronic disease groups that may lead to SOT2–5 and across organ groups posttransplant.6 However, guidelines for exercise training in SOT have not previously been published. The aim of this position statement is to provide evidence-based and expert-informed recommendations for exercise training pre- and posttransplant in adult and pediatric SOT populations and on the outcomes relevant to exercise training and physical function that should be evaluated in SOT.

Exercise refers to structured activity that is aimed at improving physical fitness or health, whereas physical activity is a broader term that encompasses any activity that requires skeletal muscle movement and increases energy expenditure.7 In addition to exercise, physical activity also includes leisure activities (eg, gardening, housework), active transportation (eg, walking to work/school or taking the stairs), and active play and sports.7 The focus of this position statement is in exercise, as the SOT literature to date has focused on structured, supervised exercise training and its effect on physical function and health outcomes. Exercise is further divided into subtypes, including aerobic training (large muscle groups, dynamic activities aimed at increasing heart rate), resistance training (activities aimed at loading isolated muscles or muscle groups to improve strength, muscular endurance, or power), flexibility (movements aimed at increasing range of motion and stretching the muscles and connective tissues), and balance training (movements aimed at challenging the vestibular, proprioceptive, and visual systems).8 Exercise training programs or “exercise prescriptions” are designed with a specific goal in mind (such as increasing aerobic capacity), and the program specifies the frequency, intensity, type, time, volume, and progression to meet this goal.8

Exercise (or aerobic) capacity is reduced in SOT candidates and recipients due to several contributing factors. In the pretransplant phase, exercise limitation can be mainly attributed to primary organ dysfunction, particularly in those with advanced heart or lung disease where circulatory or ventilatory limitations result in reduced aerobic capacity. Other factors such as anemia, deconditioning (which leads to maladaptation of skeletal muscle), muscle atrophy, weakness, malnutrition, and fatigue also contribute to exercise limitation across all types of SOT candidates, regardless of their underlying disease.9 Improvement in exercise capacity is observed posttransplant bacause of the alleviation of improved native organ function and symptoms; however, it has been shown that exercise capacity remains reduced to 40%–70% of predicted in the majority of adult and pediatric SOT recipients.9–11 Several factors can impact exercise capacity posttransplant, such as prolonged hospitalization, low physical activity levels, side effects of immunosuppressant medications (eg, corticosteroid-induced myopathy,12 mitochondrial dysfunction from calcineurin inhibitors13), ongoing skeletal muscle atrophy and weakness, and episodic illnesses (infections, rejection).14 Importantly, reduced exercise capacity and levels of physical activity in SOT candidates and recipients are key predictors of clinical outcomes before and after transplantation.15–18 However, exercise training can improve exercise capacity, and some transplant recipients reach very high levels of fitness.19,20 There are also several posttransplant complications that can be modified through exercise training, such as cardiovascular risk factors21 (hypertension, glucose dysregulation, overweight, or obesity), osteoporosis, muscle atrophy, and fatigue.22 Pretransplant exercise training improves exercise capacity of transplant candidates5 and has the potential to improve early posttransplant outcomes such as hospital length of stay.23 Despite the potential benefits of exercise training in SOT candidates and recipients, there is limited availability of dedicated transplant rehabilitation programs in Canada.24 Furthermore, a large proportion of adult and pediatric SOT recipients only engage in low levels of physical activity10,25–27 and face barriers to being physically active.25,26,28 There are currently no practice guidelines for exercise training before and after transplantation, which can limit the uptake of the research evidence into clinical practice. This position statement provides recommendations based on the current evidence and expert opinion and addresses the following questions:

  1. What is the evidence for exercise training in adults and pediatric SOT candidates and recipients?
  2. What type(s) of exercise training are recommended in the pretransplant phase?
  3. What type(s) of exercise training are recommended in the early and late posttransplant phases?
  4. What are the outcomes relevant to exercise and physical activity that should be measured pre- and posttransplant?

This position statement is in line with the research priorities identified by a Canadian Institutes of Health Research-funded meeting held in Toronto in 2013, where participants identified the development and dissemination of “expert consensus guidelines,” a key step toward improving program development and implementation.1

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MATERIALS AND METHODS

We followed the Standard Operation Procedures for developing position statements created by the Leading Clinical Practice Committee of the Canadian Society of Transplantation (CST). Before publication, this position statement was reviewed by the working group developed by the Leading Clinical Practice Committee, members of CST, as well as by the board of directors of CST. The search strategy was designed in MedLine and Pubmed to identify randomized controlled trials (RCTs) and systematic reviews of exercise interventions in solid organ (lung, heart, kidney, liver, and pancreas) transplant candidates and recipients but, when not available, all relevant study designs were reviewed. Key words included solid organ transplant, transplantation, candidates, recipients, lung, heart, liver, kidney, pancreas, exercise, physical activity, rehabilitation, and prehabilitation. Reference lists of relevant systematic reviews were also searched to identify additional studies.

In the section on exercise pretransplant in this study, we reviewed systematic reviews and studies of any design that examined the effectiveness of exercise training in SOT candidates. We also reviewed recent systematic reviews on exercise training in end-stage disease that may lead to transplantation (eg, liver cirrhosis, heart failure [HF] with left ventricular assist device [LVAD], and on extracorporeal membrane oxygenation [ECMO], as they may have included transplant candidates). Information from systematic reviews along with key studies for each organ group and expert opinion were used to provide recommendations.

For the section on exercise posttransplant in adults, we reviewed a recent systematic review and meta-analysis conducted by Janaudis-Ferreira et al,6 which included 29 RCTs examining the effects of exercise training in SOT recipients. Twenty-one of the 29 RCTs were unique studies and included a total of 736 SOT recipients (11 unique studies in kidney [n = 408]; 6 in heart [n = 198], 2 in lung [n = 50], 2 in liver [n = 80], and none in pancreas). These studies were designed to compare the effect of exercise intervention with nonexercise (control). We used Grading of Recommendations Assessment, Development, and Evaluation (The GRADE) approach of rating the quality of evidence to provide recommendations.29 The rating (high, moderate, low, or very low) reflects the confidence in the estimate of the effect to support a recommendation and considers the strengths and limitations of the body of evidence stemming from study design, risk of bias, imprecision, inconsistency, indirectness of results, and other considerations like publication bias. The GRADE approach was only used in this section due to the lack of RCTs comparing exercise to a nonexercise control in adult transplant candidates and in pediatric transplant candidates and recipients.

In pediatrics, there were no systematic reviews or RCTs in SOT candidates or recipients. Due to the lack of studies in this topic, in the pretransplant review, we identified systematic reviews and non-RCTs on exercise training in chronic conditions that lead to transplant in the pediatric population (eg, cystic fibrosis [CF], congenital heart disease, end-stage kidney disease on dialysis) to provide the reader with an overview of the evidence for exercise in these populations. In posttransplant, studies describing exercise intervention (any study design) in pediatric SOT recipients were reviewed. Recommendations were based on the best available evidence in each organ group and expert opinion.

For the outcome measure section, we reviewed a recent systematic review30 on outcome measures in RCTs of exercise interventions in SOT. We also reviewed studies that have examined the association between our outcomes of interest and important clinical endpoints in SOT adult and pediatric patients. We have provided recommendations on outcomes based on the current evidence from RCTs of exercise training and outcomes that are associated with important clinical end points as well as outcomes that are appropriate for clinical exercise prescription.

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EXERCISE TRAINING IN THE PRETRANSPLANT PHASE

The overall goal of pretransplant rehabilitation programs is to optimize physical fitness and quality of life before transplant and to improve early posttransplant outcomes such as hospital length of stay and functional independence at hospital discharge.

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Thoracic Transplants

Lung

A systematic review of exercise training in lung transplant candidates published in 20175 included 2 RCTs, 2 quasi-experimental studies, and 2 retrospective studies. Five of the 6 studies included patients with a variety of diagnoses, and 1 study only included people with chronic obstructive pulmonary disease.31

The exercise training programs in 4 studies consisted of combined aerobic training (treadmill walking and cycle ergometry) and resistance training (upper and/or lower limb exercises using free weights, machines, or body weight). One study compared continuous and interval aerobic training on a cycle ergometer31 and another used Nordic pole walking as the form of aerobic training.32 All exercise programs were supervised and took place in a hospital or institution setting.33

Most studies reported improvements in functional exercise capacity (measured by the 6-minute walk test [6MWT]) and health-related quality of life (HRQL). Only 1 study has evaluated the effect of pulmonary rehabilitation on posttransplant outcomes and reported that a greater 6-minute walk distance (6MWD) pretransplant was associated with shorter hospital length of stay.23 This was a retrospective study in which the key difference from other studies to date is that the rehabilitation program was offered for full duration of the pretransplant waiting period and there was no nonexercise (control) group.23 No studies to date have systematically defined and reported on adverse events during exercise training in lung transplant candidates, although some authors have indicated that no adverse events occurred during training.33

Following the systematic review by Hoffman et al,5 2 new studies in exercise training in lung transplant candidates have been published. Ochman et al,34 in a non-RCT, offered a 12-week Nordic walking program for lung transplant candidates. This study showed that this type of exercise was safe and feasible and that it improved functional exercise capacity, symptoms of dyspnea, and quality of life to a greater extent in the intervention group.34 A pre-post study by Singer et al35 delivered an 8-week home-based exercise program (walking + body weight exercises) plus nutritional support to 15 lung transplant candidates using an e-health application. The authors found the intervention to be acceptable to patients, safe, and capable of improving frailty scores.35

Early mobility and ambulation have been recently described in individuals on ECMO. In a systematic review including 9 studies of physiotherapy in awake people on ECMO, passive and active range of motion, bed mobility, sitting upright, and ambulation were found to be safe and feasible to conduct with a multidisciplinary team in place.36 The main risk of mobilizing patients on ECMO is risk of displacing the cannulae. As this is an emerging area of study, the evidence to date is of low quality, including only case reports and retrospective studies.36

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Heart

Two small studies37,38 examined the effects of exercise training in heart transplant candidates. These studies included individuals with end-stage HF who were awaiting heart transplantation. Ben-Gal et al,37 in a non-RCT, offered an aerobic training (cycling and walking) to 6 heart transplant candidates (originally 12 patients had been recruited, but 6 dropped out for different reasons and became the comparison group) and found significant improvements in maximal and functional exercise capacity compared with the nonexercise group. A study by Dean et al38 delivered a 4-week resistance training to end-stage HF patients who were awaiting transplantation, and although their main outcome was vasoreactivity, the authors reported data on hand grip strength, but no improvement was seen in this outcome. No adverse events were reported in the studies of Ben-Gal et al or Dean et al.37,38

Exercise training has also been studied in people supported by LVAD either as bridge to transplantation or as a destination therapy.33,39 A meta-analysis of 4 studies comparing exercise training to control in LVAD found that exercise improved VO2 peak and quality of life.39 Of the 8 studies included in the systematic review, none reported any serious adverse events from exercise training.39

Current guidelines3,40 recommend exercise training as a significant nonpharmacologic intervention in patients with symptomatic HF, to improve functional capacity and quality of life.3,40 Cochrane reviews in 2004 (n = 29 studies) and 2014 (n = 33 studies) found that exercise training in people with HF improved VO2peak, exercise duration, work capacity, 6MWD, and quality of life,41,42 led to fewer hospital admissions,42 and showed a trend toward reduced long-term mortality in the exercise training group.42 It is important to note that people with advanced HF have been underrepresented in these exercise trials.

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Abdominal Transplants

Kidney

There are only 2 published studies43,44 that examined the effects of exercise specifically in kidney transplant candidates. Gross et al,43 in an RCT, offered an 8-week program of mindfulness-based stress reduction and yoga exercises to the intervention group and telephone-based support to the control group. The primary outcome of this study was anxiety measured by the State-Trait Anxiety Inventory; the authors found no reductions in anxiety in either of the groups.43 Exercise-related outcomes were not included in this study. McAdams-DeMarco et al,44 in a pre-post study, showed that a prehabilitation program for kidney transplant candidates was feasible and that by 2 months of pre-habilitation, participants improved their physical activity by 64%.44 The authors also reported that among 5 kidney transplant candidates who received transplantation during the study period, length of stay was shorter than age-, sex-, and race-matched controls.44

Although there is a limited number of studies on exercise training that are restricted solely to individuals listed for kidney transplant, there is a large body of literature on exercise training in people with end-stage kidney disease.4,45 In these studies, exercise training was delivered during dialysis or as an outpatient or home-based program on nondialysis days, and most provided supervised training programs. The majority of studies included aerobic training alone or in combination with resistance training. A few studies included resistance training alone, and 1 study used yoga as the form of the exercise.4,45 Positive effects were seen in aerobic capacity, muscle strength, mid-thigh muscle cross-sectional area, quality of life, and heart rate variability.4 The effects on walking capacity (eg, 6MWD) and blood pressure were not significant in dialysis patients. The systematic reviews did not report on adverse events from exercise.

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Liver

There are 4 published studies46–49 that examined the effects of exercise in liver transplant candidates. Limongi et al published 2 RCTs47,48 on a specific physiotherapy program that included inspiratory muscle training as well as upper limb and abdominal exercises. The outcomes of interest in these studies were maximal inspiratory and expiratory pressure, electromyography of diaphragm and rectus abdominus muscles, and quality of life measured by the Short Form-36 (SF-36). No difference between the intervention and control groups were found in either of these studies.47,48 Debette-Gratien et al,46 in a pre-post study, offered a 12-week supervised aerobic and resistance training to 13 liver transplant candidates and showed that their program was acceptable to patients and safe. They showed significant improvements in maximal and functional exercise capacity and muscle strength but not in quality of life.46 Finally, a recent pre-post study by Williams et al49 offered a 12-week home-based exercise to patients awaiting liver transplantation and showed that their program was safe, feasible, and improved functional exercise capacity at 6 and 12 weeks. Average daily step, lower limb function (measure by the Short Physical Performance Battery [SPPB]), and quality of life improved after 12 weeks. There was no difference in anxiety and depression after the training period.49

There is also emerging evidence on exercise training in people with liver cirrhosis, a common indication for liver transplantation. A systematic review and meta-analysis by Brustia et al2 included 4 RCTs of exercise or exercise plus nutrition therapy in patients with liver cirrhosis (total of 89 patients). Exercise training consisted of supervised aerobic training (treadmill walking and cycle ergometry) in all studies; 1 study also included “kinesiotherapy” consisting of exercises to improve muscle strength, balance, and co-ordination.2 The meta-analysis revealed no significant changes in aerobic capacity (VO2 peak), functional exercise capacity (6MWD), body mass index (BMI), or thigh circumference (surrogate measure of thigh muscle mass); likely because of the small number of studies included in the analysis. Regarding liver function, no changes were observed in Model for End-stage Liver Disease (MELD) or Child scores with exercise.2 One study showed an improvement in hepatic venous pressure gradient in the exercise plus nutrition therapy versus the control group.50 No adverse outcomes were noted across studies, except for 1 patient in 1 study who experienced mild bronchospasm.51

Sarcopenia is a hallmark feature of liver cirrhosis and is associated with increased risk of mortality and morbidity in liver transplant candidates.52 A recent review suggests that multimodal exercise training (aerobic, strength, and balance training) along with nutritional interventions may improve sarcopenia and frailty in liver transplant candidates.53 However, RCTs are needed to examine the effects of these interventions on muscle mass, strength and physical function, and the potential impact on clinical outcomes such as survival.53

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Recommendations for Exercise in Adult SOT Candidates

  • There are limited trials in exercise in the pretransplant phase that specifically included adult transplant candidates. Considering the existing evidence and the opinion of the expert panel, we made some specific recommendations that are described below.
  • Exercise training in the pretransplant phase is safe and should consist of aerobic training or combined aerobic plus resistance training.
  • There is insufficient evidence to provide guidelines on the dose of exercise (frequency, intensity, type, and time) to obtain benefits in the pretransplant phase.
  • There is insufficient evidence for the program length or duration required to obtain benefits in the pretransplant phase.
  • Exercise programs should be supervised and can be conducted in a hospital (inpatient or outpatient setting). There is some evidence for home-based programs, but larger trials are needed to confirm safety and effectiveness in this setting.
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EXERCISE TRAINING IN THE POSTTRANSPLANT PHASE

The overall goal of the posttransplant rehabilitation programs is to help transplant recipients regain function, improve HRQL and participation in activities that they enjoy, as well as return to work and to their family and societal roles. Specific goals are to increase general mobility (early posttransplant) and to improve functional exercise capacity, muscle strength, HRQL, and outcomes related to cardiovascular disease and diabetes. The majority of the evidence for exercise training in transplant patients falls into the posttransplant phase and is described below by organ group and main outcome measures (maximal exercise capacity, muscle strength, and HRQL). This description is based on the findings of the systematic review by Janaudis-Ferreira et al.6 The specific timing posttransplant and characteristics of the exercise training offered in the RCTs of exercise post-SOT transplant6 are presented in Table 1. In general, the studies had low or unclear risk of bias.

Table 1

Table 1

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Thoracic Transplants

Lung

Maximal Exercise Capacity

Of the 2 RCTs in lung transplant recipients,54,55 only 154 assessed maximal exercise capacity (measured by VO2 peak). Langer et al54 offered an exercise program including aerobic as well as resistance training and showed an improvement in VO2 peak (% predicted) in the intervention group at 3 months and 1 year posttraining period. However, these improvements were not statistically significant different between groups. The authors in this study showed a statistically significant difference between the exercise and control groups in 6MWD at 3-month and 1-year follow-ups.54

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Muscle Strength

Two RCTs54,55 assessed muscle strength in lung transplant recipients following an exercise training program. Langer et al54 assessed isometric quadriceps force and showed that after a training program consisting of aerobic and resistance exercises, quadriceps force improved to a greater extent in the intervention group compared with the control group immediately after the training program (3 mo). At 1-year follow-up, the improvement from the 3 months was still greater in the intervention group compared with the control.54 A study by Mitchell et al55 delivered lumbar extension resistance training and showed a greater magnitude of change in lumbar extensor strength in the intervention group.

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Health-related Quality of Life

Only 1 RCT54 assessed HRQL (measured by the SF-36) in lung transplant recipients following an exercise training program. The authors found no between-group differences in any components of the SF-36 at 3-month follow-up, but there was a greater improvement in the intervention group in 2 subscales (physical functioning and role limitations due to physical functioning) at 1-year follow-up. The authors attributed the nondifference in HRQL at 3-month follow-up to the fact that all transplant recipients are likely to improve their self-perceived HRQL during the first 3 months after hospital discharge.54

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Heart

Maximal Exercise Capacity

Six RCTs in heart transplant recipients56–61 assessed maximal exercise capacity (measured by VO2 peak). These studies showed that exercise training improves exercise capacity in heart transplant recipients. The exercise training programs included in these studies comprised of aerobic training (continuous or interval training on a treadmill or bicycle) and/or resistance training and lasted between 3 weeks and 6 months.56–61 Only 1 study62 examined the effects of aerobic training (in this case high-intensity interval training [HIIT]), long-term posttraining (5 y). This study found that even though patients in the intervention group were able to be physically active after the training period with more than 1 hour of daily activity at a moderate intensity, this volume of activity was not sufficient to maintain the higher achievements in VO2 peak 5 years posttransplant.62 This finding suggests that some intermittent structured exercise training period may be necessary to maintain the gains achieved after the initial period of training.

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Muscle Strength

One RCT60 assessed muscle strength in heart transplant recipients after an exercise training. Nytrøen et al60 measured maximal quadriceps and hamstrings strength and showed that there was no change in maximal hamstrings strength in either the exercise or control groups. There was no change in maximal quadriceps strength between groups; however, there was a significant reduction in quadriceps strength in the control group after the training period.60 These findings were expected as this study offered HIIT on a treadmill with no resistance training component.

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Health-related Quality of Life

Of the 12 RCTs in heart transplant recipients, 3 assessed HRQL60,62,63 (measured by the SF-36). Christensen et al63 showed that an 8-week HIIT program improved the mental health subscale of the SF-36 to a greater extent in the intervention group compared with the control group. No between-group differences were observed in other subscales of the SF-36. Nytrøen et al,60 who also delivered HIIT, showed a significant difference between groups in the general health subscale of the SF-36 but not in other subscales. Yardley et al62 who reported the 5-year outcomes of the study by Nytrøen et al60 observed statistically significant differences between groups in only 1 subscale of the SF-36; the “role limitations due to physical functioning” subscale.

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Abdominal Transplants

Kidney

Maximal Exercise Capacity

Five RCTs64–68 assessed aerobic capacity (measured by VO2 max) in kidney transplant recipients following an exercise program. All studies64,66–68 except for 165 demonstrated a greater improvement in VO2 peak after the training period in the intervention group compared with the control group. These studies included both aerobic and resistance training. The study by Karelis et al,65 in which no difference between groups in VO2 peak was observed, delivered a 16-week resistance training with no aerobic component included.

O’Connor et al69 reported the long-term outcomes of the 12-week resistance or aerobic training program that was originally described in the study by Greenwood et al.64 The authors demonstrated a significant difference in relative VO2 peak between the aerobic group and control group at 9-month follow-up but not between the resistance training group and control group.69

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Muscle Strength

Four studies64,67,68,70 assessed quadriceps muscle strength in kidney transplant recipients following an exercise training program, and 3 studies64,67 demonstrated greater gains in quadriceps muscle strength in the intervention group compared with the control group. Of note, compared with the control group, Greenwood et al64 found a greater improvement in isometric quadriceps force in the group that received resistance training but not in the group that performed aerobic training. In contrast, Painter et al67 found a significantly higher improvement in quadriceps force in the intervention group even though resistance exercises were not included.

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HRQL

Five studies64,65,67,68,71 assessed HRQL (measured by either the SF-36 or the World Health Organization Five Well-Being Index) in kidney transplant recipients following an exercise training program. Of those, 3 studies65,67,71 found a greater improvement in HRQL in the intervention group compared with the control group after the training period. More specifically, these studies found a greater improvement in the intervention group in the physical,67 vitality, and general health subscales of the SF-3671 and in the general scores of the World Health Organization Five Well-Being Index.65

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Liver

Maximal Exercise Capacity

Only 1 study72 assessed maximal exercise capacity (measured by VO2 peak) in liver transplant recipients following an exercise training program. This study delivered a 24-week intervention of resistance and aerobic exercise training at a moderate-to-high intensity and showed a greater improvement in VO2 peak in the intervention group (15% increase) compared with the control group (7% increase in VO2 peak).72

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Muscle Strength

One study72 assessed muscle strength in 8 different movements (hip extension, elbow flexion/extension, shoulder flexion/extension, shoulder abduction, and knee flexion/extension) in liver transplant recipients following an exercise training program. Greater improvements were observed in hip extension and elbow flexion in the intervention compared with the control group.72

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Health-related Quality of Life

Only the study by Moya-Nájera et al72 assessed HRQL (measured by the SF-36) in liver transplant recipients after an exercise training program. All 8 subscales were improved at the end of the training period in the intervention group, while only 4 increased in the control group. However, statistically significant differences were only observed in the physical functioning and vitality subscales.72

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Safety of Exercise Training Posttransplant

Information on safety were clearly noted in a few RCTs that examined the effects of exercise post-SOT,55,58,60,64,65,68 and only 255,60 reported some adverse events. Nytrøen et al60 reported that 1 patient in the control group had a myocardial infarction and Mitchell et al55 reported a nonstatistically significant increase in rejection episodes in the exercise group.

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Recommendations for Exercise in Adult SOT Recipients

  • There is high quality of evidence that exercise training improves maximal exercise capacity, lower extremity muscle strength, and HRQL in lung, heart, kidney, and liver recipients (GRADE Recommendation Tables 2–4).
  • Exercise training in the posttransplant phase is safe and should consist of aerobic training or combined aerobic plus resistance training. To obtain benefits early or late posttransplant, exercise training should be of a moderate-to-vigorous intensity level, 3–5 times a week for a minimum of 8 weeks.
  • Early posttransplant (1–6 mo) and/or in case of medical instability, exercise programs should be supervised and can be offered in an outpatient setting or at home.
  • Late posttransplant (>6 mo), structured exercise programs, or physical activities can be unsupervised and offered at home or in private fitness centers.
Table 2

Table 2

Table 3

Table 3

Table 4

Table 4

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EXERCISE TRAINING IN PEDIATRIC SOT CANDIDATES AND RECIPIENTS

As in the adult SOT population, limitations to exercise capacity, muscle weakness, and low physical activity levels are documented in children with end-stage organ failure and posttransplant.26,73–75 While there is a paucity of exercise training studies specific to children listed for transplant, there is evidence from some studies in pediatric chronic disease conditions, such as CF and end-stage kidney disease. In the posttransplant phase, there is some evidence for the positive impact of exercise training on physical fitness and quality of life in children,74,76 but the studies are of lower quality with a lack of randomization and small sample sizes that limit their generalizability. The literature indicates that pediatric transplant recipients have low physical activity levels,77 which may result in lost opportunities for social and physical development, as well as important health benefits.78,79 Despite their complex medical needs, children posttransplant may benefit from regular participation in age-appropriate exercise, which may have a positive impact on their physical fitness and HRQL.80

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Exercise Training in the Pretransplant Phase in the Pediatric Population

Thoracic Transplants

There is limited evidence for the impact of exercise training in pediatric heart or lung transplant candidates. In pediatric heart transplant candidates (infants <1 y and children between 1 and 10 y) who are bridged to transplant with a ventricular assist device, early mobility and inpatient rehabilitation have been shown to be feasible and safe and result in improved functional capacity during the pretransplant waiting period.77,81,82 However, the level of evidence in these publications is low (case reports77,81 and small, uncontrolled study82); hence, the results must be interpreted with caution.

There have been several studies in children with CF; a primary indication for pediatric lung transplant. A recent systematic review of exercise training in CF83 included 7 studies (randomized or quasi-RCTs) exclusively in children and adolescents with CF (mean age ranges between 10 and 15 y). None of the studies specifically included individuals listed for lung transplant, and there was a broad range of disease severity among the study subjects. The majority of studies included aerobic training or aerobic plus resistance training. One study examined anaerobic (high intensity) training, and another study included inspiratory muscle training in addition to aerobic and resistance training. The length of the training programs varied widely from 2 weeks, to a large RCT of 24 months. Most studies had unclear risk of bias due to lack of reporting. Hospital- or institutional-based exercise programs had very high adherence rates (>90%), and 3 studies indicated that there were no adverse events during exercise training. Studies also showed that aerobic training was effective in improving aerobic capacity (VO2 peak or shuttle walk distance), and resistance training resulted in improved muscle strength. Combined training (aerobic plus resistance training) may, therefore, be most applicable to the pediatric CF population.

Studies of exercise training in children and adolescents (mean age range 11–16 y) with congenital heart disease (with or without surgery) have been summarized in systematic reviews.84,85 The exercise training programs included either aerobic training alone or combined aerobic and resistance training and demonstrated an improvement in aerobic capacity (VO2 peak). In the nonsurgical population, exercise did not result in any adverse effects, but this was not reported in studies of postsurgical population. No studies examined the effects of exercise training on prognostic outcomes, such as hospitalizations or survival. These results, however, cannot be directly extrapolated to heart transplant candidates as most studies include children with repaired versus palliated defects or children with a higher level of cardiovascular function than those waiting for transplant.

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Abdominal Transplants

There is very limited evidence for exercise training in pediatric kidney or liver transplant candidates, with no exercise intervention studies in children preliver transplant and small studies on exercise training in children with end-stage kidney disease. Three studies have examined exercise training in children on dialysis: 2 using intradialytic exercise76,86 and 1 using a community-based exercise program.87 The mean age of the participants in these studies ranged from 12.6 to 15.6 years. The community-based program, which included aerobic training, resistance exercises, and active games, had a very high dropout rate with only 5 out of 20 children completing the program. Intradialytic exercise consisted of 1-hour sessions of cycling and resistance exercises and was done twice weekly. Out of the 21 patients who were enrolled, 9 were not able to adhere to the program due to various reasons. Therefore, the barriers to exercise training in this population need to be addressed to improve feasibility.

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Exercise Training in the Posttransplant Phase in the Pediatric Population

Thoracic Transplants

There are a few small, nonrandomized trials examining exercise training in children following thoracic transplants. In children post-heart or lung transplant (mean age of 13 ± 3 years), a 12-week nonrandomized trial of home- or hospital-based exercise program that included aerobic, resistance, and flexibility components, resulted in increased 6MWD, proximal muscle strength (shoulder and hip), and flexibility in both groups.88 There were no significant differences between the 2 delivery modes on any of the study outcomes. In pediatric heart transplant recipients (mean age 14.7 ± 5 y), a 12-week home-based exercise program of combined aerobic and resistance training showed improvements in aerobic capacity (VO2peak) and muscle strength.89 A unique case study described an adolescent who underwent cardiac transplant at 13.6 years old and retransplant at 16.2 years old and participated in structure aerobic training after each transplant.90 Following each transplant, aerobic training resulted in improved VO2 peak; and 1 year after retransplant, VO2 peak was higher than baseline (before the first transplant).90

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Abdominal Transplants

To the best of our knowledge, there are no exercise intervention studies specific to children post-liver transplant. A study conducted in children on dialysis and post-kidney transplant (n = 44; mean age 15.1 ± 3.4 y) utilized pedometers as a motivational intervention to increase physical activity levels over a 12-week period.73 Although the improvement in steps per day did not reach significance, the change in steps per day was associated with improvements in 6MWD and self-reported physical function (based on the pediatric quality-of-life inventory [PedsQL]).73

A study was conducted in a mixed population of pediatric SOT recipients (16 thoracic and 3 abdominal transplant; mean age of 14.5 ± 2.7 y) using the World Transplant Games as an incentive to improve physical fitness.91 This study had a control group that consisted of SOT recipients (n = 14) who were not intending to participate in the Games. A home-based program of aerobic, strength, and flexibility exercises was provided, and participants took part in group-based sport training days with coaches. Between-group comparisons revealed improvements in the Progressive Aerobic Cardiovascular Endurance Run (PACER) and push-ups test in the training group. The training group also showed an improvement in physical activity level during the training period, compared with baseline. This suggest that the Games could be used as an incentive to motivate SOT recipients to engage in a structured, goal-based training program and also improve their level of physical activity.

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Recommendations for Exercise in Pediatric SOT Candidates and Recipients

  • Randomized trials of exercise training pre- and post-SOT transplant in children are needed. As the population is small, multicenter trials are needed to include a larger and representative sample. Considering the existing evidence, the expert panel made some specific recommendations that are described below.
  • Pre- and posttransplant exercise training should include a combination of aerobic, resistance, and flexibility activities. Due to the lack of evidence, specific recommendations regarding the level of supervision, type of exercise (aerobic, resistance, combined), training parameters (frequency, intensity, type, time, volume, and progression), or length of the exercise program cannot be provided.
  • Exercise programs should be individualized based on underlying pathology, the age of the child, level of experience, and developmental status. Individual barriers and motivators to exercise and physical activity need to be addressed to optimize program adherence.
  • Engagement in physical activity (eg, recreational activities, sports) should be emphasized.
  • Motor skill development should be monitored and interventions to address motor deficits need to be provided to support physical activity both pre- and post-SOT.
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OUTCOMES FOR EXERCISE AND PHYSICAL ACTIVITY IN SOT

Based on a systematic review of RCTs of exercise training SOT recipients, the most common outcome domains included in the published studies are aerobic capacity (VO2peak), muscle strength, body composition, and quality of life.30 This review also identified that most studies focus on outcomes related to body structure and function (ie, physiological impairments), and there were few outcomes related to the domains of activity or participation according to the International Classification of Functioning, Disability and Health (http://www.who.int/classifications/icf/en/). Clinically, outcome measures are used for patient evaluation and assessment to determine baseline level of function, develop an exercise training program, and track changes over time. We have provided recommendations on outcomes based on the current evidence from RCTs of exercise training, outcomes that are associated with important clinical end points in SOT patients or outcomes that are appropriate for clinical exercise prescription.

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Exercise Capacity

Aerobic capacity, which refers to the body’s ability to extract and utilize oxygen for energy or work, is the most commonly measured outcome domain in RCTs of exercise training in SOT recipients.30 In clinical practice, aerobic exercise training programs can be individually prescribed and evaluated using tests of aerobic capacity. The cardiopulmonary exercise test (CPET, conducted on a cycle ergometer or treadmill) is the gold-standard test for the measurement of peak aerobic capacity (ie, VO2peak). VO2peak is also an important marker of mortality in transplant recipients.92,93 However, the CPET is not widely available in all clinical setting as it requires technical expertise, specialized equipment, and medical supervision.8

The 6MWT, a self-paced, submaximal functional exercise test, is also used as a measure of aerobic capacity in adult SOT populations94 and an essential component of lung transplant candidacy evaluation in adults and pediatrics.95,96 6MWD has moderate correlations with VO2peak in advanced HF,97 end-stage lung disease,98 heart transplant recipients,99,100 and is a predictor of pre- and posttransplant mortality across SOT candidates.95,101,102

Both the CPET and 6MWT are also used in pediatric SOT populations. In addition, the PACER is a field test for children that has been used in pediatric transplant recipients.10,75 Other submaximal exercise tests or field walking tests (eg, incremental shuttle walk test) have not been well studied in SOT.

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Muscle Strength

Muscle strength refers to the force or tension generating capacity of a muscle8 and can be measured in several ways using a variety of instruments and procedures.103 Muscle weakness has been shown to persist from the pretransplant to posttransplant phase across organ groups.104–108 Several exercise trials include measures of upper and lower body muscle strength as a primary or secondary outcome, most commonly quadriceps (knee extensor) strength for the lower limb and handgrip strength for upper limb. Handgrip strength is also used as an indicator of overall muscle strength and has published normative values, allowing for sex- and age-specific comparisons.109,110 Handgrip strength is also a component of the Fried Frailty Index (see section on frailty). In the pediatric SOT population, field tests such the number of push-ups and sit-ups are used to evaluate upper body and core muscle strength, respectively.74

When designing a resistance-training exercise program, the 1-repetition maximum is used to evaluate strength and determine the appropriate training loads for each muscle group being trained.8,55 One-repetition maximum is also re-evaluated at regular intervals to progress resistance exercises and evaluate the effectiveness of the training program.8

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Body Composition

Anthropometric measures of body composition, including body weight, BMI, and waist circumference, as well as more advanced measures to obtain estimates of fat mass and fat-free mass using tools such as dual X-ray absorptiometry (D-XA) and bioelectrical impedance analysis, are commonly used in trials of exercise training in SOT recipients.30 In clinical practice, the use of anthropometric measures and bioelectrical impedance analysis are more feasible as they require less time, cost, and technical expertise to conduct. Although exercise training alone may only result in modest weight loss;60,71,111 body composition (low muscle mass and high fat mass), weight gain, and obesity are important concerns posttransplant especially due to the increased cardiovascular risk associated with immunosuppressant medications.112 Overweight and obesity may be linked to delayed graft function, as well as increased risk for cardiovascular disease and metabolic syndrome.113–115

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Health-related Quality of Life

HRQL is evaluated using patient-reported outcome measures (PROMs). PROMs are of particular interest in exercise interventions, as they directly capture the patient’s perspective on their health.116 In a meta-analysis, HRQL was found to improve with exercise training across 10 studies including heart, liver, and lung transplant recipients.6 The most commonly used HRQL questionnaire used in exercise trials is the SF-36, which is a generic HRQL questionnaire. In the pediatric population, the PedsQL instrument is widely used in both chronic disease and posttransplant populations.117,118

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Emerging Outcomes

There are several outcome domains that have been studied to a lesser extent in exercise trials but are associated with adverse outcomes pre- and posttransplant. These outcome domains may also be improved with exercise and physical activity but require further investigation in SOT populations.

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Metabolic and Cardiovascular Risk Factors

There is a large burden of cardiovascular disease and posttransplant diabetes in SOT recipients,119,120 which is attributed in part to immunosuppressive agents.112 In the general population, exercise and regular physical activity can reduce the risk of cardiovascular events121 and prevent cardiovascular disease risk factors, such as hypertension, dyslipidemia, and impaired glucose regulation.122 There is preliminary evidence in lung and kidney transplant recipients that some of these risk factors may improve with exercise training.54,123 However, more trials are needed to determine the optimal dose and types of exercise training that impact cardiovascular and metabolic risk in SOT.

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Frailty and Sarcopenia

There is an increasing focus on the evaluation of frailty and sarcopenia across SOT candidates and recipients, including pediatrics.124–126 Frailty and sarcopenia may be modifiable by exercise training, as shown in older adult populations127 and chronic disease,128 though these constructs have not yet been assessed as outcomes of exercise training trials in SOT. However, both frailty and sarcopenia have important associations with adverse events, such as waitlist mortality, hospital readmissions, and posttransplant mortality, across organ groups.124,129–132 In the SOT literature, frailty is commonly assessed using the Fried Frailty Index,133 which focuses on 5 key signs and symptoms and is commonly referred to as “phenotypic frailty.” Other comprehensive frailty indices134 incorporate chronic diseases, cognitive function, mental health, and socio-demographic factors; however, these have not been as well studied in SOT candidates or recipients. Emerging evidence suggests that frailty also exists in pediatric transplant candidates and there is initial work toward the development of a pediatric-specific frailty scale.126 Sarcopenia, which refers specifically to the loss of muscle mass and function associated with aging and chronic disease,135 has also been evaluated in SOT candidates and recipients. The focus of sarcopenia assessments has been on evaluating muscle mass from D-XA136,137 or single-slice CT scans to obtain abdominal,138 psoas,137,139 or thoracic muscle area.140 Sarcopenia has also been reported in pretransplant pediatric populations with kidney, liver, or intestinal failure using psoas muscle area from CT.141 A recent study in pediatric liver transplant recipients found that sarcopenia, defined by low skeletal muscle mass index from D-XA, was associated with poor growth and increased hospitalizations posttransplant.142 In adult lung transplant candidates, sarcopenia has been evaluated using the consensus definition, low muscle mass, plus one of low strength or function, in which muscle weakness was found to be more prevalent than muscle wasting.143

The evaluation of physical frailty and sarcopenia includes the assessment of mobility using functional tests such as timed sit-to-stand tests (30 or 60 s sit-to-stand; or 5 times sit-to-stand)144 or the SPPB (a composite test consisting of gait speed, tandem standing balance, and 5 times sit-to-stand).145 These functional tests are primarily dependent on the strength and function of the lower extremity muscles. They are feasible to conduct in the clinical setting as they require no specialized equipment and have little space and time requirements. In lung transplant candidates, the SPPB has been used a marker of physical frailty with a cutoff score of ≤7 out of 12 points (lower scores denoting increasing frailty).146

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Bone Health

Bone mineral density (BMD) has been studied as a primary outcome in 4 randomized trials of exercise training in SOT recipients55,111,147,148 and in several additional studies as a secondary outcome.30 No studies to date have evaluated incidence of fractures or fracture risk. Bone health is improved through specific exercise training aimed at increased loading on the bone,55,147 which may not be the goal of all exercise programs. Also, measurement of BMD and bone strength requires imaging modalities, such as D-XA, quantitative computed tomography, which are not readily available in all clinical settings and require technical expertise.

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Physical Activity

Physical activity level has been used as an outcome in a few studies of exercise training in SOT recipients.54,67 There is some evidence that structured exercise training with behavioral interventions improves physical activity levels in some chronic disease populations.149,150 Evaluation of daily physical activity can be done using self-reported questionnaires or objective measures using pedometers and accelerometers. One study also examined sedentary time,54 which is gaining more attention based on its association with cardiovascular risk in the general population. Furthermore, low levels of physical activity has been associated with increased body weight in lung transplant recipients,151 depressive symptoms,152 increased mortality in kidney27 and reduced HRQL in kidney and liver transplant recipients.153

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Motor Development

In the pediatric population, developmental motor skills are important building blocks for participation in physical activity and exercise. Motor proficiency is associated with physical activity levels in children.154,155 Children with chronic disease may demonstrate lower motor proficiency and may perceive themselves as less competent to participate in physical activity than their healthy peers, thus developing a preference for more sedentary activities.26,155 Several outcome measures have been used to assess motor development in children pre- and posttransplant, including the Mullen Scales of Early Learning, Movement ABC, Bruininks-Oseretsky Test of Motor Proficiency, and the Bayley Scales of Infant Development.

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Recommendations for Outcomes in Exercise and Physical Activity in SOT

  • Exercise (aerobic) capacity should be routinely assessed in SOT candidates and recipients using CPET (if feasible) or functional walk test, such as the 6MWT. In pediatrics, the PACER may also be used as a field test for exercise capacity in higher functioning children.
  • Muscle strength should be routinely evaluated to determine the presence of muscle weakness in pre- and posttransplant periods. Quadriceps and handgrip strength may be used as general indicators of overall lower and upper body muscle strength, respectively. In pediatrics, field tests measuring strength (curl-ups, push-ups) and the Bruininks-Oseretsky Test of Motor Proficiency can be used to compare age and gender norms.
  • Body composition using BMI and waist circumference should be included in the routine assessment of SOT candidates and recipients.
  • HRQL should be routinely evaluated using standard, PROMs such as the SF-36 (adults) or PedsQL (pediatrics).
  • Emerging outcomes, such as cardiovascular and metabolic risk factors, frailty, sarcopenia, indices of BMD, bone strength and fractures, level of physical activity, and motor development (in pediatrics), can be considered as part of the evaluation but their inclusion depends on the goals of the exercise program and the expertise of the team (Table 5).
Table 5

Table 5

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CONCLUSIONS AND RECOMMENDATIONS FOR FUTURE RESEARCH

In summary, based on the available evidence and the opinion of our expert panel, we recommend that exercise training should be offered in the pre- and posttransplant phases for both adults and children.

There are few studies (although most are not RCTs) in the pretransplant phase in adults and the available evidence is insufficient to provide specific guidelines on the dose of exercise and program duration to obtain optimal benefits. However, there is some evidence on the effectiveness and safety of exercise pretransplant that was used, along with the opinion of our expert panel, to make recommendations about exercise training for this phase of the transplantation journey. Nevertheless, larger and well-conducted trials of exercise that specifically include transplant candidates are still needed. Future studies in this topic should focus on the effects of exercise during the waiting period on waitlist outcomes, such as healthcare utilization, mortality, frailty, and early posttransplant clinical outcomes, such as hospital length of stay.

Most of the evidence for exercise training in the transplantation journey falls in the posttransplant phase. There is high quality evidence in adult to support posttransplant exercise training programs that consist of aerobic training of moderate-to-vigorous intensity, 3 to 5 times a week for a minimum of 8 weeks or combined aerobic plus resistance training. Further studies on the effects of exercise delivered long-term posttransplant (>12 mo) are needed particularly in liver and lung transplant recipients. These studies should focus on innovative strategies to enhance long-term adherence to physical activity posttransplant and on important health outcomes, such as physical activity level, cardiovascular risk factors, diabetes, graft and immune function, as well as survival.

In the pediatric population, there is no RCTs pre- or posttransplant, and there is considerable variability in the type of exercise interventions that have been studied, limiting the ability to provide specific exercise guidelines. However, based on the existing evidence in the pediatric transplant population and conditions that lead to transplantation as well as on the opinions of experts, we recommend exercise training pre- and posttransplant in the pediatric population. There is an urgent need for further studies such as multicenter RCTs (to obtain adequate sample sizes) to establish the effectiveness of exercise and the appropriate dose (type, frequency, intensity) for optimizing benefits in pediatric transplant candidates and recipients, and the impact on long-term outcomes.

Compared with other chronic diseases, such as diabetes, heart disease, and chronic obstructive pulmonary disease, the field of physical rehabilitation in SOT (specifically in kidney and liver transplantation) is understudied and, in addition, there are various barriers to implementing exercise programs in transplant centers.1,24 The importance of this position statement is that it is a key step toward raising awareness of the importance of exercise interventions in this population among transplant professionals. With increased knowledge on the benefits of exercise in the adult and pediatric transplant population, professionals will be in a better position to ensure that physical rehabilitation be an integral component of pre- and posttransplant care. Creation and implementation of these programs might be challenging specifically in a healthcare scenario, where cost is always a concern; however, creative solutions such as home-based or tele-rehabilitation programs as well as program delivery using e-health applications might address these challenges. Further research will be needed to determine the feasibility, acceptability, and effectiveness of these innovative ways of delivering exercise programs for transplant patients. Finally, another approach to address barriers related to the implementation of exercise programs and physicians’ lack of time and confidence in counseling about exercise and physical activity156 is to establish clear referral pathways for transplant patients to access qualified exercise professionals through rehabilitation centers or community-based programs.

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ACKNOWLEDGMENTS

The authors thank the Leading Clinical Practice Committee of the CST for their support in the development of this position statement. The research conducted in preparation for this position statement took place within and was supported by Canadian Network for Rehabilitation and Exercise for Solid Organ Transplant Optimal Recovery (CAN-RESTORE), which is part of the Canadian Donation and Transplantation Research Program (CDTRP). The authors thank the members of CAN-RESTORE and CST who provided valued feedback on this position statement.

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REFERENCES

1. Mathur S, Janaudis-Ferreira T, Wickerson L, et al. Meeting report: consensus recommendations for a research agenda in exercise in solid organ transplantation. Am J Transplant. 2014; 14:2235–2245
2. Brustia R, Savier E, Scatton O. Physical exercise in cirrhotic patients: towards prehabilitation on waiting list for liver transplantation. A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2018; 42:205–215
3. Ezekowitz JA, O’Meara E, McDonald MA, et al. 2017 Comprehensive update of the canadian cardiovascular society guidelines for the management of heart failure. Can J Cardiol. 2017; 33:1342–1433
4. Heiwe S, Jacobson SH. Exercise training in adults with CKD: a systematic review and meta-analysis. Am J Kidney Dis. 2014; 64:383–393
5. Hoffman M, Chaves G, Ribeiro-Samora GA, et al. Effects of pulmonary rehabilitation in lung transplant candidates: a systematic review. BMJ Open. 2017; 7:e013445
6. Janaudis-Ferreira T, Tansey CM, et al. Exercise training among solid organ transplant recipients: a systematic review and meta-analysis Transplantation. 2019 IN PRESS
7. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. 1985; 100:126–131
8. Medicine ACoS (ACSM) & Heath, WK. ACSM’s Guidelines for Exercise Testing and Prescription. 2014
9. Williams TJ, McKenna MJ. Exercise limitation following transplantation. Compr Physiol. 2012; 2:1937–1979
10. Clark CG, Cantell M, Crawford S, et al. Accelerometry-based physical activity and exercise capacity in pediatric kidney transplant patients. Pediatr Nephrol. 2012; 27:659–665
11. Dipchand AI, Manlhiot C, Russell JL, et al. Exercise capacity improves with time in pediatric heart transplant recipients. J Heart Lung Transplant. 2009; 28:585–590
12. Kanda F, Okuda S, Matsushita T, et al. Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration. Horm Res. 2001; 56 Suppl 1:24–28
13. Sanchez H, Bigard X, Veksler V, et al. Immunosuppressive treatment affects cardiac and skeletal muscle mitochondria by the toxic effect of vehicle. J Mol Cell Cardiol. 2000; 32:323–331
14. Mathur S, Reid WD, Levy RD. Exercise limitation in recipients of lung transplants. Phys Ther. 2004; 84:1178–1187
15. Martinu T, Babyak MA, O’Connell CF, et al; INSPIRE Investigators. Baseline 6-min walk distance predicts survival in lung transplant candidates. Am J Transplant. 2008; 8:1498–1505
16. Rosas SE, Reese PP, Huan Y, et al. Pretransplant physical activity predicts all-cause mortality in kidney transplant recipients. Am J Nephrol. 2012; 35:17–23
17. Walsh JR, Chambers DC, Yerkovich ST, et al. Low levels of physical activity predict worse survival to lung transplantation and poor early post-operative outcomes. J Heart Lung Transplant. 2016; 35:1041–1043
18. Zelle DM, Corpeleijn E, Stolk RP, et al. Low physical activity and risk of cardiovascular and all-cause mortality in renal transplant recipients. Clin J Am Soc Nephrol. 2011; 6:898–905
19. Haykowsky MJ, Riess K, Burton I, et al. Heart transplant recipient completes ironman triathlon 22 years after surgery. J Heart Lung Transplant. 2009; 28:415
20. Trájer E, Bosnyák E, Komka ZS, et al. Retrospective study of the hungarian national transplant team’s cardiorespiratory capacity. Transplant Proc. 2015; 47:1600–1604
21. Li C, Xu J, Qin W, et al. Meta-analysis of the effects of exercise training on markers of metabolic syndrome in solid organ transplant recipients. Prog Transplant. 2018; 28:278–287
22. Didsbury M, McGee RG, Tong A, et al. Exercise training in solid organ transplant recipients: a systematic review and meta-analysis. Transplantation. 2013; 95:679–687
23. Li M, Mathur S, Chowdhury NA, et al. Pulmonary rehabilitation in lung transplant candidates. J Heart Lung Transplant. 2013; 32:626–632
24. Trojetto T, Elliott RJ, Rashid S, et al. Availability, characteristics, and barriers of rehabilitation programs in organ transplant populations across Canada. Clin Transplant. 2011; 25:E571–E578
25. Gustaw T, Schoo E, Barbalinardo C, et al. Physical activity in solid organ transplant recipients: participation, predictors, barriers, and facilitators Clin Transplant. 2017; 31
26. Patterson C, So S, Schneiderman JE, et al. Physical activity and its correlates in children and adolescents post-liver transplant. Pediatr Transplant. 2016; 20:227–234
27. Takahashi A, Hu SL, Bostom A. Physical activity in kidney transplant recipients: a review. Am J Kidney Dis. 2018; 72:433–443
28. van Adrichem EJ, van de Zande SC, Dekker R, et al. Perceived barriers to and facilitators of physical activity in recipients of solid organ transplantation, a qualitative study. PLoS One. 2016; 11:e0162725
29. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011; 64:383–394
30. Janaudis-Ferreira T, Mathur S, Konidis S, et al. Outcomes in randomized controlled trials of exercise interventions in solid organ transplant. World J Transplant. 2016; 6:774–789
31. Gloeckl R, Halle M, Kenn K. Interval versus continuous training in lung transplant candidates: a randomized trial. J Heart Lung Transplant. 2012; 31:934–941
32. Jastrzebski D, Gumola A, Gawlik R, et al. Dyspnea and quality of life in patients with pulmonary fibrosis after six weeks of respiratory rehabilitation. J Physiol Pharmacol. 2006; 57 Suppl 4:139–148
33. Wallen MP, Skinner TL, Pavey TG, et al. Safety, adherence and efficacy of exercise training in solid-organ transplant candidates: a systematic review. Transplant Rev (Orlando). 2016; 30:218–226
34. Ochman M, Maruszewski M, Latos M, et al. Nordic walking in pulmonary rehabilitation of patients referred for lung transplantation. Transplant Proc. 2018; 50:2059–2063
35. Singer JP, Soong A, Bruun A, et al. A mobile health technology enabled home-based intervention to treat frailty in adult lung transplant candidates: a pilot study. Clin Transplant. 2018; 32:e13274
36. Polastri M, Loforte A, Dell’Amore A, et al. Physiotherapy for patients on awake extracorporeal membrane oxygenation: a systematic review. Physiother Res Int. 2016; 21:203–209
37. Ben-Gal T, Pinchas A, Zafrir N, et al. Long-term physical training in cardiac transplant candidates: is it feasible? Transplant Proc. 2000; 32:740–742
38. Dean AS, Libonati JR, Madonna D, et al. Resistance training improves vasoreactivity in end-stage heart failure patients on inotropic support. J Cardiovasc Nurs. 2011; 26:218–223
39. Ganga HV, Leung A, Jantz J, et al. Supervised exercise training versus usual care in ambulatory patients with left ventricular assist devices: a systematic review. PLoS One. 2017; 12:e0174323
40. Ponikowski P, Voors AA, Anker SD, et al; ESC Scientific Document Group. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC)developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J. 2016; 37:2129–2200
41. Rees K, Victory J, Beswick AD, et al. Cardiac rehabilitation in the UK: uptake among under-represented groups. Heart. 2005; 91:375–376
42. Taylor RS. Probiotics to prevent necrotizing enterocolitis: too cheap and easy? Paediatr Child Health. 2014; 19:351–352
43. Gross CR, Reilly-Spong M, Park T, et al. Telephone-adapted mindfulness-based stress reduction (tmbsr) for patients awaiting kidney transplantation. Contemp Clin Trials. 2017; 57:37–43
44. McAdams-DeMarco MA, Ying H, Van Pilsum Rasmussen S, et al. Prehabilitation prior to kidney transplantation: results from a pilot study. Clin Transplant. 2019; 33:e13450
45. Barcellos FC, Santos IS, Umpierre D, et al. Effects of exercise in the whole spectrum of chronic kidney disease: a systematic review. Clin Kidney J. 2015; 8:753–765
46. Debette-Gratien M, Tabouret T, Antonini MT, et al. Personalized adapted physical activity before liver transplantation: acceptability and results. Transplantation. 2015; 99:145–150
47. Limongi V, dos Santos DC, da Silva AM, et al. Effects of a respiratory physiotherapeutic program in liver transplantation candidates. Transplant Proc. 2014; 46:1775–1777
48. Limongi V, Dos Santos DC, de Oliveira da Silva AM, et al. Exercise manual for liver disease patients. World J Transplant. 2016; 6:429–436
49. Williams FR, Vallance A, Faulkner T, et al. Home-based exercise in patients awaiting liver transplantation: a feasibility study Liver Transpl. 2019
50. Macias-Rodriguez R, Torre A, Ilarraza-Lomeli H, et al. Changes on hepatic venous pressure gradient induced by a physical exercise program in cirrhotic patients: a randomized open clinical trial Hepatology. 2014; 60:246A–247A
51. Román E, García-Galcerán C, Torrades T, et al. Effects of an exercise programme on functional capacity, body composition and risk of falls in patients with cirrhosis: a randomized clinical trial. PLoS One. 2016; 11:e0151652
52. van Vugt JL, Levolger S, de Bruin RW, et al. Systematic review and meta-analysis of the impact of computed tomography-assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation. Am J Transplant. 2016; 16:2277–2292
53. Duarte-Rojo A, Ruiz-Margáin A, Montaño-Loza AJ, et al. Exercise and physical activity for patients with end-stage liver disease: improving functional status and sarcopenia while on the transplant waiting list. Liver Transpl. 2018; 24:122–139
54. Langer D, Burtin C, Schepers L, et al. Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial. Am J Transplant. 2012; 12:1584–1592
55. Mitchell MJ, Baz MA, Fulton MN, et al. Resistance training prevents vertebral osteoporosis in lung transplant recipients. Transplantation. 2003; 76:557–562
56. Bernardi L, Radaelli A, Passino C, et al. Effects of physical training on cardiovascular control after heart transplantation. Int J Cardiol. 2007; 118:356–362
57. Braith RW, Schofield RS, Hill JA, et al. Exercise training attenuates progressive decline in brachial artery reactivity in heart transplant recipients. J Heart Lung Transplant. 2008; 27:52–59
57a. Pierce GL, Schofield RS, Casey DP, et al. Effects of exercise training on forearm and calf vasodilation and proinflammatory markers in recent heart transplant recipients: a pilot study. Eur J Cardiovasc Prev Rehabil. 2008; 15:10–18
58. Haykowsky M, Taylor D, Kim D, et al. Exercise training improves aerobic capacity and skeletal muscle function in heart transplant recipients. Am J Transplant. 2009; 9:734–739
59. Hermann TS, Dall CH, Christensen SB, et al. Effect of high intensity exercise on peak oxygen uptake and endothelial function in long-term heart transplant recipients. Am J Transplant. 2011; 11:536–541
60. Nytrøen K, Rustad LA, Aukrust P, et al. High-intensity interval training improves peak oxygen uptake and muscular exercise capacity in heart transplant recipients. Am J Transplant. 2012; 12:3134–3142
61. Pascoalino LN, Ciolac EG, Tavares AC, et al. Exercise training improves ambulatory blood pressure but not arterial stiffness in heart transplant recipients. J Heart Lung Transplant. 2015; 34:693–700
62. Yardley M, Gullestad L, Bendz B, et al. Long-term effects of high-intensity interval training in heart transplant recipients: a 5-year follow-up study of a randomized controlled trial Clin Transplant. 2017; 31
63. Christensen SB, Dall CH, Prescott E, et al. A high-intensity exercise program improves exercise capacity, self-perceived health, anxiety and depression in heart transplant recipients: a randomized, controlled trial. J Heart Lung Transplant. 2012; 31:106–107
63a. Monk-Hansen T, Dall CH, Christensen SB, et al. Interval training does not modulate diastolic function in heart transplant recipients. Scand Cardiovasc J. 2014; 48
    64. Greenwood SA, Koufaki P, Mercer TH, et al. Aerobic or resistance training and pulse wave velocity in kidney transplant recipients: a 12-week pilot randomized controlled trial (the exercise in renal transplant [exert] trial). Am J Kidney Dis. 2015; 66:689–698
    64. O’Connor EM, Koufaki P, Mercer TH, et al. Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients – A pilot randomised controlled trial. PLoS One. 2017; 12:e0171063
    65. Karelis AD, Hébert MJ, Rabasa-Lhoret R, et al. Impact of resistance training on factors involved in the development of new-onset diabetes after transplantation in renal transplant recipients: an open randomized pilot study. Can J Diabetes. 2016; 40:382–388
    65a. Shakoor E, Salesi M, Koushki M, et al. The effect of concurrent aerobic and anaerobic exercise on stress, anxiety, depressive symptoms, and blood pressure in renal transplant female patients: A randomized control trial. Int J Kin Sport Sci. 2016; 4:25–31
      66. Kouidi E, Vergoulas G, Anifanti M, et al. A randomized controlled trial of exercise training on cardiovascular and autonomic function among renal transplant recipients. Nephrol Dial Transplant. 2013; 28:1294–1305
      67. Painter PL, Hector L, Ray K, et al. A randomized trial of exercise training after renal transplantation. Transplantation. 2002; 74:42–48
      67a. Pooranfar S, Shakoor E, Shafahi MJ, et al. The effect of exercise training on quality and quantity of sleep and lipid profile in renal transplant patients: a randomized clinical trial. Int J Org Transplant Med. 2014; 5:157164
        67b. Riess KJ, Haykowsky M, Lawrance R, et al. Exercise training improves aerobic capacity, muscle strength, and quality of life in renal transplant recipients. Appl Physiol Nutr Metab. 2014; 39:566–571
          68. Riess KJ, Haykowsky M, Lawrance R, et al. Exercise training improves aerobic capacity, muscle strength, and quality of life in renal transplant recipients. Appl Physiol Nutr Metab. 2014; 39:566–571
          69. O’Connor EM, Koufaki P, Mercer TH, et al. Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients – a pilot randomised controlled trial. PLoS One. 2017; 12:e0171063
          70. Leasure R, Belknap D, Burks C, Schlegel J. The effects of structured exercise on muscle mass, strength, and endurance of immunosuppressed adult renal transplant patients: a pilot study Rehabilitation Nursing Research. 1995; 4:47–57
          71. Tzvetanov I, West-Thielke P, D’Amico G, et al. A novel and personalized rehabilitation program for obese kidney transplant recipients. Transplant Proc. 2014; 46:3431–3437
          72. Moya-Nájear D, Moya-Herraiz A, Compte-Torrero L, et al. Combined resistance and endurance training at a moderate-to-high intensity improves physical condition and quality of life in liver transplant patients Liver Transpl. 2017; 23:1273–1281
          73. Akber A, Portale AA, Johansen KL. Use of pedometers to increase physical activity among children and adolescents with chronic kidney disease. Pediatr Nephrol. 2014; 29:1395–1402
          74. Krasnoff JB, Mathias R, Rosenthal P, et al. The comprehensive assessment of physical fitness in children following kidney and liver transplantation. Transplantation. 2006; 82:211–217
          75. Unnithan VB, Veehof SH, Rosenthal P, et al. Fitness testing of pediatric liver transplant recipients. Liver Transpl. 2001; 7:206–212
          76. Paglialonga F, Lopopolo A, Scarfia RV, et al. Correlates of exercise capacity in pediatric patients on chronic hemodialysis. J Ren Nutr. 2013; 23:380–386
          77. Lombard KA. Physical therapy for a child poststroke with a left ventricular assist device. Pediatr Phys Ther. 2016; 28:126–132
          78. Eime RM, Young JA, Harvey JT, et al. A systematic review of the psychological and social benefits of participation in sport for children and adolescents: informing development of a conceptual model of health through sport. Int J Behav Nutr Phys Act. 2013; 10:98
          79. Moola F, Fusco C, Kirsh JA. “What I wish you knew”: social barriers toward physical activity in youth with congenital heart disease (CHD). Adapt Phys Activ Q. 2011; 28:56–77
          80. Marker AM, Steele RG, Noser AE. Physical activity and health-related quality of life in children and adolescents: a systematic review and meta-analysis. Health Psychol. 2018; 37:893–903
          81. Amao R, Imamura T, Sawada Y, et al. Experiences with aggressive cardiac rehabilitation in pediatric patients receiving mechanical circulatory supports. Int Heart J. 2016; 57:769–772
          82. Hollander SA, Hollander AJ, Rizzuto S, et al. An inpatient rehabilitation program utilizing standardized care pathways after paracorporeal ventricular assist device placement in children. J Heart Lung Transplant. 2014; 33:587–592
          83. Radtke T, Nevitt SJ, Hebestreit H, Kriemler S. Physical exercise training for cystic fibrosis Cochrane Database Syst Rev. 2017; 11:CD002768
          84. Gomes-Neto M, Saquetto MB, da Silva e Silva CM, et al. Impact of exercise training in aerobic capacity and pulmonary function in children and adolescents after congenital heart disease surgery: a systematic review with meta-analysis. Pediatr Cardiol. 2016; 37:217–224
          85. Tikkanen AU, Oyaga AR, Riaño OA, et al. Paediatric cardiac rehabilitation in congenital heart disease: a systematic review. Cardiol Young. 2012; 22:241–250
          86. Goldstein SL, Montgomery LR. A pilot study of twice-weekly exercise during hemodialysis in children. Pediatr Nephrol. 2009; 24:833–839
          87. van Bergen M, Takken T, Engelbert R, et al. Exercise training in pediatric patients with end-stage renal disease. Pediatr Nephrol. 2009; 24:619–622
          88. Deliva RD, Hassall A, Manlhiot C, et al. Effects of an acute, outpatient physiotherapy exercise program following pediatric heart or lung transplantation. Pediatr Transplant. 2012; 16:879–886
          89. Patel JN, Kavey RE, Pophal SG, et al. Improved exercise performance in pediatric heart transplant recipients after home exercise training. Pediatr Transplant. 2008; 12:336–340
          90. Chang KV, Chiu HH, Wang SS, et al. Cardiac rehabilitation in a pediatric patient with heart retransplantation. A single case study. Eur J Phys Rehabil Med. 2014; 50:199–205
          91. Deliva RD, Patterson C, So S, et al. The world transplant games: an incentive to improve physical fitness and habitual activity in pediatric solid organ transplant recipients. Pediatr Transplant. 2014; 18:889–895
          92. Ting SM, Iqbal H, Kanji H, et al. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. J Am Soc Nephrol. 2014; 25:187–195
          93. Yardley M, Havik OE, Grov I, et al. Peak oxygen uptake and self-reported physical health are strong predictors of long-term survival after heart transplantation. Clin Transplant. 2016; 30:161–169
          94. Tomczak CR, Warburton DE, Riess KJ, et al. Pulmonary oxygen uptake and heart rate kinetics during the six-minute walk test in transplant recipients. Transplantation. 2008; 85:29–35
          95. Castleberry A, Mulvihill MS, Yerokun BA, et al. The utility of 6-minute walk distance in predicting waitlist mortality for lung transplant candidates. J Heart Lung Transplant. 2017; 36:780–786
          96. Yimlamai D, Freiberger DA, Gould A, et al. Pretransplant six-minute walk test predicts peri- and post-operative outcomes after pediatric lung transplantation. Pediatr Transplant. 2013; 17:34–40
          97. Cahalin LP, Mathier MA, Semigran MJ, et al. The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure. Chest. 1996; 110:325–332
          98. Cahalin L, Pappagianopoulos P, Prevost S, et al. The relationship of the 6-min walk test to maximal oxygen consumption in transplant candidates with end-stage lung disease. Chest. 1995; 108:452–459
          99. Chen SY, Lu PC, Lan C, et al. Six-minute walk test among heart transplant recipients. Transplant Proc. 2014; 46:929–933
          100. Doutreleau S, Di Marco P, Talha S, et al. Can the six-minute walk test predict peak oxygen uptake in men with heart transplant? Arch Phys Med Rehabil. 2009; 90:51–57
          101. Carey EJ, Steidley DE, Aqel BA, et al. Six-minute walk distance predicts mortality in liver transplant candidates. Liver Transpl. 2010; 16:1373–1378
          102. Lederer DJ, Arcasoy SM, Wilt JS, et al. Six-minute-walk distance predicts waiting list survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006; 174:659–664
          103. Mathur S, Dechman G, Bui KL, et al. Evaluation of limb muscle strength and function in people with chronic obstructive pulmonary disease Cardio Phys Therap J. 2018; 30:24–34
          104. Braith RW, Limacher MC, Leggett SH, et al. Skeletal muscle strength in heart transplant recipients. J Heart Lung Transplant. 1993; 126 Pt 11018–1023
          105. Mizuno Y, Ito S, Hattori K, et al. Changes in muscle strength and six-minute walk distance before and after living donor liver transplantation. Transplant Proc. 2016; 48:3348–3355
          106. Schaufelberger M, Eriksson BO, Lönn L, et al. Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation. Eur J Heart Fail. 2001; 3:59–67
          107. van den Ham EC, Kooman JP, Schols AM, et al. Similarities in skeletal muscle strength and exercise capacity between renal transplant and hemodialysis patients. Am J Transplant. 2005; 5:1957–1965
          108. Walsh JR, Chambers DC, Davis RJ, et al. Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength. Clin Transplant. 2013; 27:E504–E511
          109. Massy-Westropp NM, Gill TK, Taylor AW, et al. Hand grip strength: age and gender stratified normative data in a population-based study. BMC Res Notes. 2011; 4:127
          110. Mathiowetz V, Kashman N, Volland G, et al. Grip and pinch strength: normative data for adults. Arch Phys Med Rehabil. 1985; 66:69–74
          111. Krasnoff JB, Vintro AQ, Ascher NL, et al. A randomized trial of exercise and dietary counseling after liver transplantation. Am J Transplant. 2006; 6:1896–1905
          112. Miller LW. Cardiovascular toxicities of immunosuppressive agents. Am J Transplant. 2002; 2:807–818
          113. Courivaud C, Kazory A, Simula-Faivre D, et al. Metabolic syndrome and atherosclerotic events in renal transplant recipients. Transplantation. 2007; 83:1577–1581
          114. Meier-Kriesche HU, Arndorfer JA, Kaplan B. The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation. 2002; 73:70–74
          115. Nicoletto BB, Fonseca NK, Manfro RC, et al. Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis. Transplantation. 2014; 98:167–176
          116. Deshpande PR, Rajan S, Sudeepthi BL, Abdul Nazir CP. Patient-reported outcomes: a new era in clinical research Perspect Clin Res. 2011; 2:137–1144
          117. Hamiwka LA, Cantell M, Crawford S, et al. Physical activity and health related quality of life in children following kidney transplantation. Pediatr Transplant. 2009; 13:861–867
          118. Parent JJ, Sterrett L, Caldwell R, et al. Quality of life following paediatric heart transplant: are age and activity level factors? Cardiol Young. 2015; 25:476–480
          119. Jardine AG, Gaston RS, Fellstrom BC, et al. Prevention of cardiovascular disease in adult recipients of kidney transplants. Lancet. 2011; 378:1419–1427
          120. Pham PT, Pham PM, Pham SV, et al. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011; 4:175–186
          121. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. Jama. 2009; 301:2024–2035
          122. Lin X, Zhang X, Guo J, et al. Effects of exercise training on cardiorespiratory fitness and biomarkers of cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials J Am Heart Assoc. 2015; 4:e002014
          123. Painter PL, Hector L, Ray K, et al. Effects of exercise training on coronary heart disease risk factors in renal transplant recipients. Am J Kidney Dis. 2003; 42:362–369
          124. Kahn J, Wagner D, Homfeld N, et al. Both sarcopenia and frailty determine suitability of patients for liver transplantation – a systematic review and meta-analysis of the literature Clin Transplant. 2018; 32:e13226
          124a. Juskowa J, Lewandowska M, Bartlomiejczyk B, et al. Physical rehabilitation and risk of atherosclerosis after successful kidney transplantation. Transplant Proc. 2006; 38:157–160
          125. Rozenberg D, Wickerson L, Singer LG, et al. Sarcopenia in lung transplantation: a systematic review. J Heart Lung Transplant. 2014; 33:1203–1212
          126. Lurz E, Quammie C, Englesbe M, et al. Frailty in children with liver disease: a prospective multicenter study. J Pediatr. 2018; 194:109–115.e4
          127. de Labra C, Guimaraes-Pinheiro C, Maseda A, et al. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials. BMC Geriatr. 2015; 15:154
          128. Maddocks M, Kon SS, Canavan JL, et al. Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study. Thorax. 2016; 71:988–995
          129. Jha SR, Hannu MK, Chang S, et al. The prevalence and prognostic significance of frailty in patients with advanced heart failure referred for heart transplantation. Transplantation. 2016; 100:429–436
          130. McAdams-DeMarco MA, Law A, King E, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant. 2015; 15:149–154
          131. McAdams-DeMarco MA, Ying H, Olorundare I, et al. Individual frailty components and mortality in kidney transplant recipients. Transplantation. 2017; 101:2126–2132
          132. Singer JP, Diamond JM, Anderson MR, et al. Frailty phenotypes and mortality after lung transplantation: a prospective cohort study. Am J Transplant. 2018; 18:1995–2004
          133. Fried LP, Tangen CM, Walston J, et al; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56:M146–M156
          134. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. Cmaj. 2005; 173:489–495
          135. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: report of the european working group on sarcopenia in older people. Age Ageing. 2010; 39:412–423
          136. Singer JP, Peterson ER, Snyder ME, et al. Body composition and mortality after adult lung transplantation in the United States. Am J Respir Crit Care Med. 2014; 190:1012–1021
          137. Yanishi M, Kinoshita H, Tsukaguchi H, et al. Dual energy X-ray absorptiometry and bioimpedance analysis are clinically useful for measuring muscle mass in kidney transplant recipients with sarcopenia. Transplant Proc. 2018; 50:150–154
          138. Tandon P, Ney M, Irwin I, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012; 18:1209–1216
          139. Englesbe MJ, Patel SP, He K, et al. Sarcopenia and mortality after liver transplantation. J Am Coll Surg. 2010; 211:271–278
          140. Rozenberg D, Mathur S, Herridge M, et al. Thoracic muscle cross-sectional area is associated with hospital length of stay post lung transplantation: a retrospective cohort study. Transpl Int. 2017; 30:713–724
          141. Mangus RS, Bush WJ, Miller C, et al. Severe sarcopenia and increased fat stores in pediatric patients with liver, kidney, or intestine failure. J Pediatr Gastroenterol Nutr. 2017; 65:579–583
          142. Mager DR, Hager A, Ooi PH, et al. Persistence of sarcopenia after pediatric liver transplantation is associated with poorer growth and recurrent hospital admissions. JPEN J Parenter Enteral Nutr. 2019; 43:271–280
          143. Rozenberg D, Singer LG, Herridge M, et al. Evaluation of skeletal muscle function in lung transplant candidates. Transplantation. 2017; 101:2183–2191
          144. Vaidya T, Chambellan A, de Bisschop C. Sit-to-stand tests for COPD: a literature review. Respir Med. 2017; 128:70–77
          145. Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994; 49:M85–M94
          146. Singer JP, Diamond JM, Gries CJ, et al. Frailty phenotypes, disability, and outcomes in adult candidates for lung transplantation. Am J Respir Crit Care Med. 2015; 192:1325–1334
          147. Braith RW, Mills RM, Welsch MA, et al. Resistance exercise training restores bone mineral density in heart transplant recipients. J Am Coll Cardiol. 1996; 28:1471–1477
          148. Eatemadololama A, Karimi MT, Rahnama N, et al. Resistance exercise training restores bone mineral density in renal transplant recipients. Clin Cases Miner Bone Metab. 2017; 14:157–160
          148a. Basha MA, Mowafy ZE, Morsy EA. Sarcopenic obesity and dyslipidemia response to selective exercise program after liver transplantation. Egypt J Med Hum Gen. 2015; 16:263–268
            149. Lahham A, McDonald CF, Holland AE. Exercise training alone or with the addition of activity counseling improves physical activity levels in COPD: a systematic review and meta-analysis of randomized controlled trials. Int J Chron Obstruct Pulmon Dis. 2016; 11:3121–3136
            150. Mosalman Haghighi M, Mavros Y, Fiatarone Singh MA. The effects of structured exercise or lifestyle behavior interventions on long-term physical activity level and health outcomes in individuals with type 2 diabetes: a systematic review, meta-analysis, and meta-regression. J Phys Act Health. 2018; 15:697–707
            151. Bossenbroek L, den Ouden ME, de Greef MH, et al. Determinants of overweight and obesity in lung transplant recipients. Respiration. 2011; 82:28–35
            152. Spaderna H, Zahn D, Schulze Schleithoff S, et al. Depression and disease severity as correlates of everyday physical activity in heart transplant candidates. Transpl Int. 2010; 23:813–822
            153. Painter P, Krasnoff J, Paul SM, et al. Physical activity and health-related quality of life in liver transplant recipients. Liver Transpl. 2001; 7:213–219
            154. Kambas A, Michalopoulou M, Fatouros IG, et al. The relationship between motor proficiency and pedometer-determined physical activity in young children. Pediatr Exerc Sci. 2012; 24:34–44
            155. Stodden DF, Goodway JD, Langendorfer SJ, et al. A Developmental perspective on the role of motor skill competence in physical activity: an emergent relationship Quest. 2008; 60:290–306
            156. Pang A, Lingham S, Zhao W, et al. Physician practice patterns and barriers to counselling on physical activity in solid organ transplant recipients. Ann Transplant. 2018; 23:345–359
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