Study design

ECSERT (a pilot randomised controlled trial of a structured, home-based Exercise programme on Cardiovascular StructurE and function in Renal Transplant recipients) was a prospective, randomised, open-label, blinded endpoint (PROBE) feasibility study performed at one renal unit in the United Kingdom (prospectively registered: ClinicalTrials.gov [NCT04123951]). The full trial protocol and primary outcome (feasibility) results are reported elsewhere [16,17]. In summary, 50 KTRs were randomised (1:1) to either; (1) a 12-week home-based combined aerobic and resistance exercise programme (n = 25) or; (2) control (n = 25; receiving guideline-directed care). Outcomes were assessed at baseline and after 12 weeks [16]. Ethical and regulatory approval was obtained from the East Midlands-Nottingham 2 research ethics committee and the Health Research Authority (Ref: 19/EM/0209). Participants were recruited between 09/03/2020 and 16/02/2023, and provided written informed consent in the presence of research trial staff.

This manuscript reports the feasibility results from the primary manuscript (n = 50) [17], alongside new data from the qualitative analysis of semi-structured interviews (n = 12) with intervention participants (i.e., those that undertook the 12-week structured home-based exercise intervention). Integrated mixed methods analyses was used to explore the primary findings to provide insights and suggestions for future definitive trials and programmes of exercise in KTRs.

Participants and recruitment

Full eligibility criteria for the ECSERT trial have been described elsewhere [16]. In summary, stable adult KTR (>1 year) at increased cardiometabolic risk, willing and able to consent, and able to safely perform exercise training and testing were eligible.

Participants from the intervention group were invited (by post) to be interviewed by phone or video call (whilst the participant was at home), or in-person (in a private room on a hospital site) after completion of the 12-week exercise programme. The predetermined purposive sampling framework included age, sex, kidney function, and intervention adherence to ensure maximum variation [20]. The minimum target sample size was 12: suggested by several studies and a recent review, to be in line with ‘typical’ sample sizes for phenomenological studies to yield saturation (where the addition of more data does not yield additional insights or issues) [21–23]. Three months after completing the exercise programme, participants who completed an initial interview were contacted for an additional semi-structured one-to-one telephone interview to explore the impact of the programme, if any, on subsequent maintenance of lifestyle and exercise habits.

Exercise programme and control

In brief, the 12-week, home-based, structured exercise programme included aerobic and resistance training (4–5 sessions in total per week). The aerobic component of the programme was walking, jogging, cycling, or similar, depending on resources available and participant preference. Participants were asked to complete 2–3 sessions per week using a rating of perceived of exertion (RPE) of 13–15 (somewhat hard-hard) for 20–30 min. The resistance component of the exercise programme included a combination of 6–8 exercises per session chosen by the participant from a pool of twelve exercises (to provide variety) targeting upper and lower body and core muscle groups, using free weights and/or resistance bands. The chosen pool of exercises included: squat, hip abduction, lunge, calf-raise, side-lunge, bicep-curl, bent-over row, reverse-fly, lateral-raise, chest-press, side-bends, and standing trunk rotation. Participants were asked to complete 6–8 resistance exercises twice a week (but not on consecutive days to allow appropriate recovery). Initially, they were advised to complete 1–2 sets of 10 repetitions (at 60% 1-repetition maximum [RM]), gradually increasing to 3–6 sets of 10 repetitions with a minimum of 30 sec rest between sets. Whilst participants could do aerobic and resistance sessions on the same day if they wished, they were advised to have at least one day in between resistance sessions for recovery. Participants were provided with an exercise diary which included additional instructions, dumbbells and resistance bands, and access to educational and instructional videos. Participants received a telephone call from a member of the research team every two weeks in order to discuss progression of the exercise and address any issues. Participants continued to receive guideline-directed care as did all participants randomised to the control group.

Outcome measures

At baseline and after 12 weeks participants completed the following outcome measures: cardiopulmonary exercise test (CPET), cardiac magnetic resonance imaging (MRI), physical function (timed-up-and-go [TUAG]; gait speed; sit-to-stand-60 [STS-60]), balance and postural stability, physical activity (via accelerometery), handgrip strength, lower limb strength (via isokinetic dynamometry), body composition (via bioelectrical impendence), muscle size (via MRI and ultrasound), blood and urine analysis, and self-reported questionnaires. Full details have previously been reported [16].

Qualitative data collection

Interviews were conducted via telephone, video call, or in-person depending on participant preference and COVID-19 restrictions. Post-intervention interviews were conducted by one researcher independent to the ECSERT trial (HMLY) to reduce bias and encourage honest and open responses. The researcher kept a reflexive diary to record comments and thoughts during and after the interviews and during data analysis. The topic guide was predetermined but amended after two interviews by REB and HMLY after discussion about question flow (S1 File). Questions covered: (1) the acceptability of the design and conduct of the trial, and (2) the acceptability of the ECSERT exercise programme including exercise enjoyment, difficulties encountered, perceived advantages and disadvantages of the programme. Interviews were digitally recorded, anonymised, transcribed verbatim, and imported into NVivo, Version 20.6.1.1137 for Windows (QRS International, Massachusetts, USA) which was used as a data management tool.

Qualitative analysis approach

This study was conducted using a phenomenological approach to explore the lived experience of participants. Reflexive thematic analysis was used to identify themes at a semantic level [24]. Two researchers independently coded two transcripts (REB and HMLY) followed by collaborative review to ensure consistent interpretation and improved credibility prior to REB conducting the rest of the analysis. REB and HMLY refined final theme names for consistency. Illustrative quotes are labelled with sex and age (‘*’ and ‘**’ distinguish two participants of the same age). Code frequency counts were used to determine saturation; when the frequency of new codes diminished with few or no more codes identified. Where any new codes were identified in later transcripts, higher-order groupings (namely salient themes) where checked for relevance. If new codes were incorporated into existing salient themes, saturation criteria were satisfied.

Research team and reflexivity

At the time of interviews REB (female) was a Clinical Trials Facilitator with a BSc (hons) in Sports Science and an MPhil in qualitative research. As REB was the main facilitator for the ECSERT trial, all interviews were carried out by HMLY (female) as participants were more likely to be open about their experiences. Similarly, REB conducted all aspects of the trial including outcome measures and exercise programme monitoring, therefore would likely have some prior perceptions. HMLY was a Specialist Renal Research Physiotherapist and an NIHR Development and Skills Enhancement Fellow with BSc (Hons), MSc, and PhD qualifications. HMLY had extensive skills and experience in conducting qualitative research. Participants were only aware of HMLY’s position as a researcher and physiotherapist and no prior relationship was established. HMLY was only aware that participants had taken part in the ECSERT exercise programme.

Mixed methods analysis

A convergent mixed methods analysis was used [25], where quantitative and qualitative data collection and analyses occurred separately and in parallel before being integrated. This method allows the individual strengths of each method to prevail efficiently, and allows a comprehensive understanding of the research question. A joint display was developed to visually portray how the two datasets converged, diverged, or expanded [25,26].

Quantitative (feasibility)

Quantitative feasibility data are reported in the primary manuscript [17]. To summarise, 171 patients were screened and 94 (55%) were eligible and invited to take part in the study. Fifty of those invited (53%) were recruited across 22 months of recruitment. Consented participant characteristics were: age 50 ± 14 years (INT 49 ± 13; CTR 51 ± 15), 23 male (INT 10; CTR 13), eGFR 59 ± 19 mL/min/1.73m² (INT 60 ± 20; CTR 61 ± 21), 35 White British (WB), 13 South Asian (SA), 1 Caribbean, and 1 Mixed ethnicity (INT 17 WB, 7 SA, 1 Mixed; CTR 18 WB, 6 SA, 1 Caribbean). Intervention participants (n = 22 completed) recorded an average of 4.4 ± 1.4 exercise sessions per week (aerobic 2.8 ± 1.1; strength 1.6 ± 0.5). Three participants withdrew from the intervention group (1 COVID-19 infection, 1 recurrent urine infections unrelated to the trial, 1 time/family circumstances) and one from the control group (lost to follow-up; 8% attrition). There were no serious adverse events reported.

Qualitative

Fourteen ECSERT intervention group participants were approached, of which 12 agreed to complete qualitative interviews (both immediate post-intervention and at 3 months). Two participants declined to participate. Baseline characteristics are summarised in Table 1 and individual exercise programme adherence in S2 Table in S1 File. Interviews were completed between June 2021 and December 2022 with a median duration of 51 min (IQR 43–54). S3.1-S3.3 Tables in S1 File provide additional quotations for themes outlined in the coming sections.

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Table 1. Baseline demographics and clinical characteristics of interview participants.

https://doi.org/10.1371/journal.pone.0336620.t001

Trial design and procedures

Table 2 outlines the themes and related quotations for qualitative results relating to the trial design and procedures.

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Table 2. Themes relating to the ECSERT trial design and procedures.

https://doi.org/10.1371/journal.pone.0336620.t002

Exercise programme

Acceptability of the exercise aids and programme delivery.

Table 3 outlines the example quotations for qualitative results relating to the acceptability of the exercise aids and programme delivery.

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Table 3. Acceptability of the exercise aids and programme delivery.

https://doi.org/10.1371/journal.pone.0336620.t003

The majority of participants highlighted that the exercise diary was useful and straightforward to complete and was enough to understand what was required for the exercise programme. One participant liked that the diary felt personal (e.g., individual starting weights for each resistance exercise were given during the instructional session). Other participants reported that being able to track progress, and make adjustments over time was encouraging. Participants described the resistance exercise videos as a useful supplement to the exercise diary, helping to confirm that they were performing exercises correctly. Some participants described the rating of perceived exertion (RPE) scale as informative to gauge how hard they were working and others felt that it was subjective and vague. Participants found the instructional session (performed via video call after the baseline assessment visit) helpful when combined with the exercise diary. Some participants would have preferred to have someone present to correct exercise technique. Other participants felt the presence of someone may have helped them feel motivated to exercise. Two participants did not like exercising at home, preferring to go elsewhere as it provided them with an obligation to attend.

Barriers to exercise session completion.

Table 4 outlines the themes and related example quotations for qualitative results relating to the barriers to exercise session completion.

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Table 4. Barriers and facilitators to exercise session completion and maintenance of activity.

https://doi.org/10.1371/journal.pone.0336620.t004

Theme 1: Finding the motivation, making the personal commitment: Many participants described the biggest barrier to completing the exercise sessions as not having the personal motivation. This was particularly referenced in relation to the resistance exercises, which they found the most challenging. Some also felt that there were other distractions at home, including family obligations.

Theme 2: Frequent illness and other health conditions: There were a multitude of conditions and ailments described which included musculoskeletal pain and discomfort, swelling, infections, and breathing problems. These put limitations largely on the intensity of the exercise that participants could perform and, in some cases, reduced the number of resistance exercises that were appropriate from the pool of 12. A number of participants who had fistulas in place from previous dialysis therapy, highlighted a fear of lifting heavy weights. Almost all participants reported either an illness or multiple illnesses, a hospital procedure, or hospitalisation during their 12-week intervention period. Whilst these in themselves resulted in missed exercise sessions, participants described ‘getting back into’ the exercise as challenging as they could not always restart where they paused. Many needed to make adjustments to their programme. This was described as frustrating and demotivating as were existing health conditions which affected the amount or type of exercise that they could do.

Mixed methods analysis

The mixed methods analysis facilitated the understanding of the recently published primary feasibility findings [17]. Table 5 shows the joint display of the qualitative and quantitative datasets. The ECSERT trial and exercise programme were shown to be feasible, meeting a-priori recruitment, retention, and adherence criteria. The qualitative dataset provides complementary reasoning for successful recruitment, reasons for rates of attrition and supportive information for the successful programme adherence, alongside potential barriers and suggestions for the maintenance of long-term engagement. Whilst outcome measure completion was quantitatively high, qualitative data presents an indication of the least and most important measures to participants. A summary of suggestions for progression to a definitive trial are presented in Table 6.

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Table 5. Joint display with feasibility and qualitative results.

https://doi.org/10.1371/journal.pone.0336620.t005

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Table 6. Summary of suggestion for moving forward to a definitive trial.

https://doi.org/10.1371/journal.pone.0336620.t006

Trial design and procedures

Participants stressed the importance of the initial contact being from a clinician which provided the security that the trial was linked to a trusted person which likely led to the successful recruitment rates. The perception that clinicians, and more specifically a patient’s own clinician, are most successful in recruiting to clinical trials has been previously explored in several populations. Qualitative interviews conducted in clinical trials teams revealed that recruitment was more successful in trials where a clinician had mentioned the study prior to the research nurse providing more details, even if the study was observational [27]. From the perspective of KTRs and trials of exercise, the importance of clinicians’ approval is seemingly fundamental across all modes of exercise [6,28,29]. Many KTRs would not partake in exercise programmes or trials without the approval of their clinician to ensure they will not harm their transplant.

Outcome measure completion was high and the qualitative results provide valuable insight and further detail into the participant perspectives. The CPET is one of the most common measures to be used in exercise trials of solid organ transplant recipients (SOTR) [30,31], and calls have been made to consider functional exercise capacity tests that are more relevant to daily life and are less costly and resource-intensive [31]. However, in the present study, whilst completion was the lowest (but still high) for this outcome, participants described it as the most beneficial. It provided reassurance prior to exercising independently at home and tangible results where progress could be monitored post-intervention. The latter was an important facilitator for exercise maintenance and continuation. Whilst the perception of the benefits of exercise can sometimes be enough to motivate continuation, the inclusion of understandable and interpretable measures can support these perceptions [32]. There was discordance between the high questionnaire completion rates and the qualitative perspectives. Future studies should consider which questionnaires are the most important, valid, and reliable to measure the desired outcomes. This will prevent overburdening the participants and avoid inaccurate completion. There have been several calls for a core outcomes set of standardised outcome measures for exercise and physical activity research in both SOTR [31] and patients living with CKD and kidney transplants specifically [33]. Care should be taken to seek the opinions of KTRs directly in the development of these outcome sets, as research and patient priorities can differ substantially.

Exercise programme

Every participant valued the exercise diary as it allowed a quick and efficient way of documenting progression week-by-week. Lahham et al. concluded that a diary was an acceptable and valid way to ascertain exercise participation after comparing with an objective measure during the final week of their 8-week home-based exercise programme in pulmonary rehabilitation [34]. A systematic review of 14 exercise trials in people with various health conditions investigated exercise adherence and outcomes when instructions were provided using a multimedia approach compared with verbal and written [35]. They concluded that multimedia approaches to exercise instruction may increase exercise adherence but evidence was insufficient to determine whether there was any impact on outcomes [35]. The qualitative results in the current study support the use of multimedia approaches to exercise instruction as participants found the additional instructional videos helpful to aid participation.

There were polarised views regarding instructional sessions and/or the exercise programme including some supervised (in-person) elements. Opinions were clearer for the instructional session(s) with many participants believing that seeing the exercises live and reinforcing correct technique would be beneficial. Although in many cases, the videos, diaries, and phone calls were sufficient without any in-person elements. Concern during the programme about physical ability was the only neutral response received within the patient satisfaction questionnaire (previously published [17]) which could be addressed by in-person instructional sessions to build confidence. This is supported by previous qualitative work in which KTRs with less confidence and experience of exercise desired supervised exercise sessions to build confidence; this was not required long-term [6].

A key barrier to exercise session completion was illness and/or symptoms of comorbidities [17], which is further explored in this qualitative work. Participants reported difficulty with restarting exercise after a bout of illness or hospital procedure, particularly as the sessions were home-based and fear of negative consequences was high. Given the frequent nature of illness in this population, programmes should include methods that help participants regain pre-illness levels of exercise. This may be in the form of an in-person session(s) to rebuild confidence in ability and reduce worry. Similarly, comorbid conditions, particularly musculoskeletal, were troublesome. Participants made use of the flexibility of the programme, particularly the bigger pool of resistance exercises to choose from to mitigate some effects. Future studies should continue to provide adaptable and varied exercise to avoid discomfort whilst exercising. Whilst less comorbidities have been identified as being predictive of exercise adherence in home-based studies [36], some of the difficulties explained by participants point to a potential need for education or direction by their healthcare professionals. For example, fear of lifting weights with the fistula arm can lead to overprotection and underuse and restriction to daily activities which can reduced QoL [37]. A systematic review suggested that arm exercise training actually promotes arteriovenous fistula (AVF) clinical and ultrasonographic maturation [38]. Similar fears were expressed around exercise with osteoporosis.

Participants who observed changes reported being more motivated to continue exercising. For participants lacking in self-motivation, as discussed, initial in-person sessions or some in-person training sessions may be a way to encourage self-motivation during home-based exercise programmes. Participants reported improvements in strength, stamina, fatigue, and mental health and seemed to place the highest value on improvements that impacted daily life, such as less fatigue and ability to work longer. Some of the most potent reasons for exercise participation have been previously identified as maintaining independence [39] and increasing daily activity performance [40].

Low self-motivation was one of the biggest challenges to completing the exercise sessions, particularly as they were largely self-directed. Lack of self-motivation was previously identified as a barrier to exercise in KTRs [6]. An umbrella review of 55 studies assessing the key factors associated with adherence to physical exercise in patients with chronic disease and older adults identified social support as a crucial factor in continued exercise [32]. Telephone calls every two weeks were viewed as motivational and necessary to continued home-based exercise participation. Regular communication has been identified as a factor that may influence physical activity in the short- and long-term [32]. In a study of 104 adults with chronic health conditions, those who received gym-based exercise and home-based exercise supplemented with telephone support achieved similar outcomes [41]. Whilst telephone calls require additional resources, they may have contributed to the high exercise adherence in the current study and these (or similar approaches) appear fundamental to the success of home-based programmes. Similarly, participants spoke of the motivational benefits of familial support. Bachmann et al. identified studies whereby low support were associated with lower home-based exercise adherence [42]. Future home-based programmes and trials of exercise may consider how family members and telephone communications might be utilised in a sustainable clinical setting as useful methods of support.

Getting into a routine, the flexibility of home-based exercise, and the variety of options were important factors for exercise session completion. Collado-Mateo et al. identified that integration into daily living was strongly associated with higher activity adherence [32]. Whilst many factors are at play in the transformation of physical activity into a lifestyle habit, the authors highlighted that their background and the preferences of participants were the most crucial, and only programmes that are in line with these can be successful.

Long-term engagement with exercise

Many participants had continued with some elements of the programme, usually the ones which they enjoyed the most, and/or ones that they had integrated into their daily routine. The importance of routine was discussed as a facilitator to exercise session completion, but it appears to be an important factor during the transition to longer-term engagement. A Cochrane review comparing home- and centre-based programmes in older adults found that participants were more likely to adhere to home-based programmes in the longer-term compared to centre-based [43]. In trials with a follow-up of ≥ 12 months exploring exercise in patients with coronary heart disease, there was a small but significant difference in exercise capacity in favour of the home-based exercise [44]. This supports in-person sessions being supplementary to a predominantly home-based programme.

Suggestions by participants for encouraging long-term engagement with exercise after the programme included many of the elements of the facilitators of exercise session completion previously mentioned, such as monitoring of progress. Suggestions were repeated CPET testing, check-in phone calls, yearly reviews with repeated assessments, and continued support from someone close to the nephrology department with exercise experience (e.g., a physio or exercise physiologist). In a systematic review of 11 studies assessing interventions to achieve ongoing adherence for adults with chronic conditions following a supervised exercise programme, there were no significant differences in long-term adherence between intervention types (centre-based, home exercise with telephone follow-up, home exercise with no follow-up, and weaning-based programmes) [45]. This is perhaps indicative that longer-term engagement is entirely personal and future programmes may wish to include a multitude of options.

Strengths and limitations

A key strength of this study is the mixed methods analyses, allowing for further explanation of the feasibility of the ECSERT trial design and procedures, and the exercise programme [17]. Equal importance of both datasets was ensured by the concurrent collection and analysis before integration [25,26]. Qualitative data collection by an independent researcher and reflexivity diaries supported qualitative rigour. As with most trials of physical activity, it is likely that the sample were somewhat already motivated to exercise and therefore the results may not be generalisable. Effort should be made to engage participants who do not participate in any form of physical activity as the applicability to this subgroup of the population remains uncertain. Some factors of the trial design could not be explored as participants from the control group were not interviewed. Finally, there is a lack of quantitative data on maintenance activity to explore whether qualitative findings aligned. This data was not collected due to limited resource.

Clinical implications

The development and implementation of rehabilitation programmes within healthcare systems has been described as essential [46], yet implementation in CKD in particular is extremely low despite the inherent benefits to health and QoL [47]. The ECSERT study results provide clear recommendations for the delivery of home-based rehabilitation which can be adopted for different healthcare settings through the inclusion of key recommendations for programme components. A clear progressive programme with a variety of activity options and a method of documenting progress (written or multimedia) is essential. Support with integrating activity into daily routine supports long-term engagement, as does structured assessments, monitoring, and support from healthcare professionals. Instructional sessions (largely required in-person) ensure a strong foundation to engage in activity in a home setting with confidence. Methods of supporting the return to activity after illness, procedures, or hospitalisation to prevent drop-off and return to inactivity should be considered an integral part of any programme. The inclusion of these components should be considered in the design and delivery of any home-based programme to encourage success.