Diagnostic accuracy of a 'sarcopenia index' based on serum biomarkers creatinine and cystatin C in 458,702 UK Biobank participants.

BACKGROUND & AIMS: There is an emerging and urgent need to identify biomarkers of sarcopenia. A novel sarcopenia index (SI), based on serum creatinine and cystatin C, has emerged as a potential biomarker for use. The SI can predict clinical outcomes and discriminate between the presence of sarcopenia in a range of chronic and acute conditions. However, the SI has not yet been tested in a large real-world general population dataset. This study aimed to investigate the accuracy of the SI in the identification of sarcopenia in a large prospective general population cohort. METHODS: Data were taken from UK Biobank, a large prospective epidemiological study in the United Kingdom (UK). Serum creatinine and cystatin C values were used to calculate the SI [creatinine (mg/dl)/cystatin C (mg/dl) × 100]. Probable sarcopenia was defined by maximum handgrip strength (HGS). Muscle mass was assessed using bioelectrical impedance analysis. Low muscle mass was defined as an appendicular lean mass (ALM) index below prespecified thresholds. Confirmed sarcopenia was defined as both low HGS and low muscle mass. Pearson correlation coefficients and logistic regression were used to explore the association between various sarcopenia traits (probable sarcopenia, low ALM index, and confirmed sarcopenia) and the SI. The diagnostic value of the SI was investigated using the area under the receiver operating characteristic curve (area under the curve, AUC). RESULTS: 458,702 participants were included in the analysis (46.4% males, mean age, males: 68.7 (±8.2) years; females: 68.2 (±8.0) years)). Probable sarcopenia was observed in 4.5% of males and 6.1% of females; low ALM index in 2.8% of males and 0.7% of females; confirmed sarcopenia in 0.3% of males and 0.1% of females. SI was significantly lower in individuals with confirmed sarcopenia (males: 86.3 ± 16.6 vs. 99.5 ± 15.3, p < .01; females: 73.6 ± 13.7 vs. 84.6 ± 14.0, p < .01). For every 1-unit increase in the SI, the odds of confirmed sarcopenia were reduced by 5% in males (odds ratio (OR): 0.95, p < 0.001) and 7% in females (OR: 0.923, p < 0.001). The AUC showed acceptable discriminative ability of confirmed sarcopenia (males: AUC = 0.731; females: AUC = 0.711). CONCLUSIONS: Using a large real-world dataset of almost half a million people, our study indicated the SI has acceptable diagnostic accuracy when identifying those with sarcopenia and may be a useful biomarker to aid the stratification of those at risk and in need of intervention.

Skeletal Muscle Texture Assessment Using Ultrasonography: Comparison with Magnetic Resonance Imaging in Chronic Kidney Disease.

Skeletal muscle dysfunction is common in chronic kidney disease (CKD). Of interest is the concept of "muscle quality," of which measures include ultrasound-derived echo intensity (EI). Alternative parameters of muscle texture, for example, gray level of co-occurrence matrix (GCLM), are available and may circumvent limitations in EI. The validity of EI is limited in humans, particularly in chronic diseases. This study aimed to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Images of the thigh were acquired using a 3 Tesla MRI scanner. Quantification of muscle (contractile), fat (non-contractile), and miscellaneous (connective tissue, fascia) components were estimated. Anatomical rectus femoris cross-sectional area was measured using B-mode 2D ultrasonography. To assess muscle texture, first (i.e., EI)- and second (i.e., GLCM)-order statistical analyses were performed. Fourteen participants with CKD were included (age: 58.0 ± 11.9 years, 50% male, eGFR: 27.0 ± 7.4 ml/min/1.73m2, 55% Stage 4). Higher EI was associated with lower muscle % (quadriceps: ß = -.568, p = .034; hamstrings: ß = -.644, p = .010). Higher EI was associated with a higher fat % in the hamstrings (ß = -.626, p = .017). A higher angular second moment from GLCM analysis was associated with greater muscle % (ß = .570, p = .033) and lower fat % (ß = -.534, p = .049). A higher inverse difference moment was associated with greater muscle % (ß = .610, p = .021 and lower fat % (ß = -.599, p = .024). This is the first study to investigate the associations between ultrasound-derived parameters of muscle texture with MRI. Our preliminary findings suggest ultrasound-derived texture analysis provides a novel indicator of reduced skeletal muscle % and thus increased intramuscular fat.

Lifestyle interventions delivered by eHealth in chronic kidney disease: A scoping review.

A method of overcoming barriers associated with implementing lifestyle interventions in CKD may be through the use of eHealth technologies. The aim of this review was to provide an up-to-date overview of the literature on this topic. Four bibliographical databases, two trial registers, and one database for conference proceedings were searched from inception to August 2023. Studies were eligible if they reported a lifestyle intervention using eHealth technologies. A narrative synthesis of the findings from the included studies structured around the type of eHealth intervention was presented. Where a sufficient number of studies overlapped in terms of the type of intervention and outcome measure these were brought together in a direction of effect plot. There were 54 included articles, of which 23 were randomised controlled trials (RCTs). The main component of the intervention for the included studies was mobile applications (n = 23), with the majority being in the dialysis population (n = 22). The majority of eHealth interventions were reported to be feasible and acceptable to participants. However, there was limited evidence that they were efficacious in improving clinical outcomes with the exception of blood pressure, intradialytic weight gain, potassium, and sodium. Although eHealth interventions appear acceptable and feasible to participants, there is insufficient evidence to make recommendations for specific interventions to be implemented into clinical care. Properly powered RCTs which not only demonstrate efficacy, but also address barriers to implementation are needed to enhance widespread adoption.

Improving self-management behaviour through a digital lifestyle intervention: An internal pilot study.

BACKGROUND: Self-management is a key component of successful chronic kidney disease (CKD) management. Here, we present the findings from the internal pilot of a multicentre randomised controlled trial (RCT) aimed to test the effect of a digital self-management programme ('My Kidneys & Me' (MK&M)). METHODS: Participants (aged ≥18 years and CKD stages 3-4) were recruited from hospital kidney services across England. Study processes were completed virtually. Participants were randomised 2:1 to either intervention (MK&M) or control group. The first 60 participants recruited were included in a 10-week internal pilot which assessed study feasibility and acceptability against pre-specified progression criteria: 1) eligibility and recruitment, acceptability of 2) randomisation and 3) outcomes, 4) MK&M activation, and 5) retention and attrition rates. Semi-structured interviews further explored views on trial participation. RESULTS: Of the 60 participants recruited, 41 were randomised to MK&M and 19 to control. All participants completed baseline measures and 62% (n=37) completed post-intervention outcome measures. All progression criteria met the minimum thresholds to proceed. Nine participants were interviewed. The themes identified were satisfaction with study recruitment processes (openness to participate, reading and agreeing to "terms and conditions"), acceptability of study design (remote study participation, acceptability of randomisation, completion of online assessment(s)), and methods to improve recruitment and retention (personalised approach, follow-up communication). CONCLUSION: This internal pilot demonstrated the feasibility and acceptability of a virtually run RCT. Progression criteria thresholds to proceed to the definitive RCT were met. Areas for improvement were identified and protocol amendments were made to improve trial delivery.

Novel Approach to Intradialytic Progressive Resistance Exercise Training.

Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

Digital health interventions in chronic kidney disease: levelling the playing field?

Digital health interventions (DHIs) have long been thought of as a convenient way to deliver aspects of healthcare and broaden access to services. For patients with chronic kidney disease (CKD), DHIs designed to improve health literacy, self-efficacy and health-related behaviours such as physical activity, diet and adherence have been developed and are being tested, but their translation into clinical practice will be challenging. While DHIs potentially have broad reach, it is increasingly clear that patients from lower socio-economic and educational backgrounds, minority ethnic groups, elderly patients and those who face digital poverty are the least likely to access and benefit from DHIs, when they are precisely the patients who stand to gain the most. This article discusses the potential for DHIs to level the playing field for patients with CKD as well as the steps researchers, clinicians and developers should consider ensuring DHIs are developed, in collaboration with patients, to be inclusive and effective, as well as strategies that should be considered during development to support translation into practice.

The Potential Modulatory Effects of Exercise on Skeletal Muscle Redox Status in Chronic Kidney Disease.

Chronic Kidney Disease (CKD) is a global health burden with high mortality and health costs. CKD patients exhibit lower cardiorespiratory and muscular fitness, strongly associated with morbidity/mortality, which is exacerbated when they reach the need for renal replacement therapies (RRT). Muscle wasting in CKD has been associated with an inflammatory/oxidative status affecting the resident cells' microenvironment, decreasing repair capacity and leading to atrophy. Exercise may help counteracting such effects; however, the molecular mechanisms remain uncertain. Thus, trying to pinpoint and understand these mechanisms is of particular interest. This review will start with a general background about myogenesis, followed by an overview of the impact of redox imbalance as a mechanism of muscle wasting in CKD, with focus on the modulatory effect of exercise on the skeletal muscle microenvironment.

Perceptions and Experiences of High-Intensity Interval Training in Kidney Transplant Recipients: A Big HIIT?

High-intensity interval training (HIIT) is considered a novel and time-efficient method to reduce cardiovascular disease risk, a leading cause of mortality in kidney transplant recipients. However, research in this population is severely limited. The aim of this study was to understand kidney transplant recipients' perceptions and experiences of HIIT and their readiness to participate in HIIT. Individual, semi-structured interviews were conducted in adults with a kidney transplant (n = 13; 53±13 years). Interviews were audiorecorded, transcribed verbatim, and subjected to framework analysis. Overall, participants had a good knowledge of HIIT and were open to participation. Acknowledgment of the superior benefits to cardiovascular, mental, and general health, as well as the lower time commitment, were all motivators for participation. There were some heightened concerns around damaging the kidney and 'knowing your limits. Personalization, physician's approval, and supervision were all important factors in participation. This study provides evidence that HIIT would be, in principle, largely accepted by recipients of a kidney transplant. However, several considerations are also identified in the present study, which would be essential to the success of any future efficacy trial or rehabilitation program.

Multimorbidity prevalence and patterns in chronic kidney disease: findings from an observational multicentre UK cohort study.

PURPOSE: Multimorbidity [defined as two or more long-term conditions (LTCs)] contributes to increased treatment and medication burden, poor health-related quality of life, and worse outcomes. Management strategies need to be patient centred and tailored depending on existing comorbidities; however, little is known about the prevalence and patterns of comorbidities in people with chronic kidney disease (CKD). We investigated the prevalence of multimorbidity and comorbidity patterns across all CKD stages. METHODS: Multimorbidity was assessed, using a composite of self-report and clinical data, across four CKD groups stratified by eGFR [stage 1-2, stage 3a&b, stage 4-5, and kidney transplant (KTx)]. Principal component analysis using varimax rotation was used to identify comorbidity clusters across each group. RESULTS: Of the 978 participants (mean 66.3 ± 14 years, 60% male), 96.0% had multimorbidity. In addition to CKD, the mean number of comorbidities was 3.0 ± 1.7. Complex multimorbidity (i.e. ≥ 4 multiple LTCs) was identified in 560 (57.3%) participants. When stratified by CKD stage, the two most prevalent comorbidities across all stages were hypertension (> 55%) and musculoskeletal disorders (> 40%). The next most prevalent comorbidity for CKD stages 1-2 was lung conditions and for CKD stages 3 and 4-5 it was heart problems. CKD stages 1-2 showed different comorbidity patterns and clustering compared to other CKD stages. CONCLUSION: Most people across the spectrum of CKD have multimorbidity. Different patterns of multimorbidity exist at different stages of CKD, and as such, clinicians should consider patient comorbidities to integrate care and provide effective treatment strategies.

Individual frailty phenotype components and mortality in adults with type 2 diabetes: A UK Biobank study.

AIMS: This study aimed to explore associations between frailty components and mortality and rank prognostic relevance of each frailty component in predicting mortality in adults with and without type 2 diabetes (T2D). METHODS: We used data from the UK Biobank. Associations and prognostic discrimination of individual Fried's frailty components and the overall frailty status with all-cause and cardiovascular (CVD) mortality were investigated using Cox proportional-hazard models and C-index in adults with and without T2D. RESULTS: In both populations the strongest association with all-cause mortality across all frailty components and overall frailty status was observed for slow walking pace (without T2D Hazard Ratio [HR] 2.25, 95 %CI: 2.12-2.38 and with T2D HR 1.95, 95 %CI: 1.67-2.28). Similarly, slow walking pace was associated with a greater risk of CVD mortality. The combination of T2D and slow walking pace had the strongest association with all-cause and CVD mortality, compared to the combination of T2D and other frailty components or overall frailty status. Slow walking pace also provided the greatest prognostic discrimination. CONCLUSION: Slow walking pace has a stronger predictive factor for all-cause and CVD mortality compared to other frailty components and overall frailty status, especially when simultaneously present with T2D.

The Codevelopment of "My Kidneys & Me": A Digital Self-management Program for People With Chronic Kidney Disease.

BACKGROUND: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. OBJECTIVE: This work describes the systematic codevelopment of "My Kidneys & Me" (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). METHODS: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. RESULTS: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. CONCLUSIONS: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial.

'Self-Management Intervention through Lifestyle Education for Kidney health' (the SMILE-K study): protocol for a single-blind longitudinal randomised controlled trial with nested pilot study.

INTRODUCTION: Many people living with chronic kidney disease (CKD) are expected to self-manage their condition. Patient activation is the term given to describe the knowledge, skills and confidence a person has in managing their own health and is closely related to the engagement in preventive health behaviours. Self-management interventions have the potential to improve remote disease management and health outcomes. We are testing an evidence-based and theory-based digital self-management structured 10-week programme developed for peoples with CKD called 'My Kidneys & Me'. The primary aim of the study (Self-Management Intervention through Lifestyle Education for Kidney health (SMILE-K)) is to assess the effect on patient activation levels. METHODS AND ANALYSIS: A single-blind randomised controlled trial (RCT) with a nested pilot study will assess the feasibility of the intervention and study design before continuation to a full RCT. Individuals aged 18 years or older, with established CKD stage 3-4 (eGFR of 15-59 mL/min/1.73 m2) will be recruited through both primary and secondary care pathways. Participants will be randomised into two groups: intervention group (receive My Kidneys & Me in addition to usual care) and control group (usual care). The primary outcome of the nested pilot study is feasibility and the primary outcome of the full RCT is the Patient Activation Measu (PAM-13). The full RCT will assess the effect of the programme on online self-reported outcomes which will be assessed at baseline, after 10 weeks, and then after 20 weeks in both groups. A total sample size of N=432 participants are required based on a 2:1 randomisation. A substudy will measure physiological changes (eg, muscle mass, physical function) and patient experience (qualitative semi-structured interviews). ETHICS AND DISSEMINATION: This study was fully approved by the Research Ethics Committee-Leicester South on the 19 November 2020 (reference: 17/EM/0357). All participants are required to provide informed consent obtained online. The results are expected to be published in scientific journals and presented at clinical research conferences. This is protocol version 1.0 dated 27 January 2021. TRIAL REGISTRATION NUMBER: ISRCTN18314195.

Living with frailty and haemodialysis: a qualitative study.

BACKGROUND: Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. METHODS: Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4-7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. RESULTS: Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4-5), and 11 moderately or severely frail (CFS 6-7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants' accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). CONCLUSIONS: The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. TRIAL REGISTRATION: ISRCTN12840463 .

Associations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease.

BACKGROUND: Frailty is characterized by the loss of biological reserves and vulnerability to adverse outcomes. In individuals with chronic kidney disease (CKD), numerous pathophysiological factors may be responsible for frailty development including inflammation, physical inactivity, reduced energy intake, and metabolic acidosis. Given that both CKD and frailty incur a significant healthcare burden, it is important to understand the relationship of CKD and frailty in real-world routine clinical practice, and how simple frailty assessment methods (e.g. frailty indexes) may be useful. We investigated the risk of frailty development in CKD and the impact of frailty status on mortality and end-stage kidney disease (ESKD). METHODS: A retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the UK Office for National Statistics was undertaken in 819 893 participants aged ≥40 years, of which 140 674 had CKD. Frailty was defined using an electronic frailty index, generated electronically from primary care records. Cox proportional hazard and flexible parametric survival models were used to investigate the risk of developing frailty and the effect of frailty on risk of all-cause and cardiovascular mortality, and ESKD. RESULTS: The mean age of those with CKD was 77.5 (SD 9.7) years [61.0 (SD 12.1) years in no-CKD group]; 62.0% of the CKD group were female (compared with 53.3% in no-CKD group). The mean estimated glomerular filtration rate of those with CKD was 46.1 (SD 9.9) mL/min/1.73 m2 . The majority of those with CKD (75.3%) were frail [vs. 45.4% in those without CKD (no-CKD)]. Over 3 years (median), 69.5% of those with CKD developed frailty. Compared with no-CKD, those with CKD had increased rates of developing mild (hazard ratio: 1.02; 95% confidence interval: 1.01-1.04), moderate (1.30; 1.26-1.34), and severe (1.50; 1.37-1.65) frailty. Mild (1.22; 1.19-1.24), moderate (1.60; 1.56-1.63), and severe (2.16; 2.11-2.22) frailty was associated with increased rates of all-cause and cardiovascular-related mortality (mild 1.35; 1.31-1.39; moderate 1.96; 1.90-2.02; and severe 2.91; 2.81-3.02). All stages of frailty significantly increased ESKD rates. CONCLUSIONS: Frailty is highly prevalent and associated with adverse outcomes in people with CKD, including mortality and risk of ESKD. Preventative interventions should be initiated to mitigate the development of frailty. The use of a simple frailty index, generated electronically from health records, can predict outcomes and may aid prioritization for management of people with frailty.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

Feasibility and acceptability of high-intensity interval training and moderate-intensity continuous training in kidney transplant recipients: the PACE-KD study.

BACKGROUND: Kidney transplant recipients (KTRs) exhibit unique elevated inflammation, impaired immune function, and increased cardiovascular risk. Although exercise reduces cardiovascular risk, there is limited research on this population, particularly surrounding novel high-intensity interval training (HIIT). The purpose of this pilot study was to determine the feasibility and acceptability of HIIT in KTRs. METHODS: Twenty KTRs (male 14; eGFR 58±19 mL/min/1.73 m2; age 49±11 years) were randomised and completed one of three trials: HIIT A (4-, 2-, and 1-min intervals; 80-90% watts at V̇O2peak), HIITB (4×4 min intervals; 80-90% V̇O2peak) or MICT (~40 min; 50-60% V̇O2peak) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 weeks) and followed up for 3 months. Feasibility was assessed by recruitment, retention, and intervention acceptability and adherence. RESULTS: Twenty participants completed the intervention, and 8 of whom achieved the required intensity based on power output (HIIT A, 0/6 [0%]; HIITB, 3/8 [38%]; MICT, 5/6 [83%]). Participants completed 92% of the 24 sessions with 105 cancelled and rescheduled sessions and an average of 10 weeks to complete the intervention. Pre-intervention versus post-intervention V̇O2peak (mL/kg-1/min-1) was 24.28±4.91 versus 27.06±4.82 in HIITA, 24.65±7.67 versus 27.48±8.23 in HIIT B, and 29.33±9.04 versus 33.05±9.90 in MICT. No adverse events were reported. CONCLUSIONS: This is the first study to report the feasibility of HIIT in KTRs. Although participants struggled to achieve the required intensity (power), this study highlights the potential that exercise has to reduce cardiovascular risk in KTRs. HIIT and MICT performed on a cycle, with some modification, could be considered safe and feasible in KTRs. Larger scale trials are required to assess the efficacy of HIIT in KTRs and in particular identify the most appropriate intensities, recovery periods, and session duration. Some flexibility in delivery, such as incorporating home-based sessions, may need to be considered to improve recruitment and retention. TRIAL REGISTRATION: ISRCTN, ISRCTN17122775 . Registered on 30 January 2017.

A qualitative exploration of the facilitators and barriers to self-management in kidney transplant recipients.

BACKGROUND: Understanding the behaviours that facilitate or impede one's ability to self-manage is important to improve health-related outcomes in kidney transplant recipients (KTRs). Previous studies exploring the self-management experiences of KTRs have focused on specific tasks (e.g., medication adherence), age groups (e.g., adolescent or older recipients), or have been conducted outside of the UK where transferability of findings is unknown. Our study aimed to explore the perceptions and experiences of self-management in UK KTRs to identify facilitators and barriers associated with self-management tasks. METHODS: Semi-structured interviews were conducted with eleven KTRs. Topics explored included experiences of self-management tasks (diet, exercise, medications, stress management), perceived healthcare role, and future interventional approaches. Thematic analysis was used to identify and report themes. RESULTS: Eight themes were identified which were mapped onto the three self-management tasks described by Corbin and Strauss: medical, role and emotional management. Perceived facilitators to self-management were: gathering health-related knowledge, building relationships with healthcare professionals, creating routines within daily life, setting goals and identifying motivators, establishing support networks, and support from family and friends. Complexity of required treatment and adjusting to a new health status were perceived barriers to self-management. CONCLUSIONS: Participants described the importance of collaborative consultations and continuity of care. Tailored interventions should identify individualised goals and motivators for participating in self-management. Education on effective strategies to manage symptoms and comorbidities could help alleviate KTRs' perceived treatment burden. Family and peer support could emotionally support KTRs; however, managing the emotional burden of transplantation warrants more attention.

Effect of high intensity interval training and moderate intensity continuous training on lymphoid, myeloid and inflammatory cells in kidney transplant recipients.

Kidney transplantations are seen to be a double-edge sword. Transplantations help to partially restore renal function, however there are a number of health-related co-morbidities associated with transplantation. Cardiovascular disease (CVD), malignancy and infections all limit patient and graft survival. Immunosuppressive medications alter innate and adaptive immunity and can result in immune dysfunction. Over suppression of the immune system can result in infections whereas under suppression can result in graft rejection. Exercise is a known therapeutic intervention with many physiological benefits. Its effects on immune function are not well characterised and may include both positive and negative influences depending on the type, intensity, and duration of the exercise bout. High intensity interval training (HIIT) has become more popular due to it resulting in improvements to tradional and inflammatory markers of cardiovascular (CV) risk in clinical and non-clinical populations. Though these improvements are similar to those seen with moderate intensity exercise, HIIT requires a shorter overall time commitment, whilst improvements can also be seen even with a reduced exercise volume. The purpose of this study was to explore the physiolocial and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in kidney transplan recipients (KTRs). In addition, the natural variations of immune and inflammatory cells in KTRs and non-CKD controls over a longitudinal period are explored. Newly developed multi-colour flow cytometry methods were devised to identify and characterise immune cell populations. Twenty-six KTRs were randomised into one of two HIIT protocols or MICT: HIIT A (n=8; 4-, 2-, and 1-min intervals; 80-90% VO2peak), HIIT B (n=8, 4x4 min intervals; 80-90% VO2peak), or MICT (n=8, ~40 min; 50-60% VO2peak) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 ± 2 weeks). Blood samples taken pre-training, mid training, post-training and 3 months later. Novel multi-colour flow cytometric panels were developed to characterise lymphoid and myeloid cell population from peripheral blood mononuclear cells. No changes were observed for circulating immune and inflammatory cells over the 8-week interventions. The feasibility study does not suggest that exercise programmes using HIIT and MICT protocols elicit adverse negative effects on immunity in KTRs. Therefore, such protocols may be immunologically safe for these patients. The inability of the participants to achieve the target exercise intensities may be due to physiological abnormalities in this population which warrants further investigation.

The Impact of Falls: A Qualitative Study of the Experiences of People Receiving Haemodialysis.

The prevalence of falls is high in people receiving haemodialysis (HD). This study aimed to explore the experiences of people receiving HD who had fallen in the last six months. A qualitative study, informed by constructivist grounded theory, used semi-structured interviews in combination with falls diaries. Twenty-five adults (mean age of 69 ± 10 years, 13 female, 13 White British) receiving HD with a history of at least one fall in the last six months (median 3, IQR 2-4) participated. Data were organised within three themes: (a) participants' perceptions of the cause of their fall(s): poor balance, weakness, and dizziness, exacerbated by environmental causes, (b) the consequences of the fall: injuries were disproportionate to the severity of the fall leading to loss of confidence, function and disruptions to HD, (c) reporting and coping with falls: most did not receive any specific care regarding falls. Those who attended falls services reported access barriers. In response, personal coping strategies included avoidance, vigilance, and resignation. These findings indicate that a greater focus on proactively identifying falls, comprehensive assessment, and timely access to appropriate falls prevention programmes is required to improve care and outcomes.