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.

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.

Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population.

BACKGROUND: Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. METHODS: Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. RESULTS: In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was 'feeling tired'; and 4) being female independently increased the likelihood of reporting more symptoms. CONCLUSIONS: Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. TRIAL REGISTRATION: The study was registered prospectively as ISRCTN11596292 .

Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study.

BACKGROUND: People with chronic kidney disease (CKD) report high levels of physical inactivity, a major modifiable risk factor for morbidity and mortality. Understanding the biological, psychosocial and demographic causes of physical activity behaviour is essential for the development and improvement of potential health interventions and promotional initiatives. This study investigated the prevalence of physical inactivity and determined individual correlates of this behaviour in a large sample of patients across the spectrum of kidney disease. METHODS: A total of 5656 people across all stages of CKD (1-2, 3, 4-5, haemodialysis, peritoneal dialysis and renal transplant recipients) were recruited from 17 sites in England from July 2012 to October 2018. Physical activity was evaluated using the General Practice Physical Activity Questionnaire. Self-reported cardiorespiratory fitness, self-efficacy and stage of change were also assessed. Binominal generalized linear mutually adjusted models were conducted to explore the associations between physical activity and correlate variables. This cross-sectional observational multi-centre study was registered retrospectively as ISRCTN87066351 (October 2015). RESULTS: The prevalence of physical activity (6-34%) was low and worsened with disease progression. Being older, female and having a greater number of comorbidities were associated with greater odds of being physically inactive. Higher haemoglobin, cardiorespiratory fitness and self-efficacy levels were associated with increased odds of being active. Neither ethnicity nor smoking history had any effect on physical activity. CONCLUSIONS: Levels of physical inactivity are high across all stages of CKD. The identification of stage-specific correlates of physical activity may help to prioritize factors in target groups of kidney patients and improve the development and improvement of public health interventions.

Utility of Ultrasound as a Valid and Accurate Diagnostic Tool for Sarcopenia: Sex-Specific Cutoff Values in Chronic Kidney Disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) have aberrant changes in body composition, including low skeletal muscle mass, a feature of "sarcopenia." The measurement of the (quadriceps) rectus femoris (RF) cross-sectional area (CSA) is widely used as a marker of muscle size. Cutoff values are needed to help discriminate the condition of an individual's muscle (eg, presence of sarcopenia) quickly and accurately. This could help distinguish those at greater risk and aid in targeted treatment programs. METHODS: Transverse images of the RF were obtained by B-mode 2-dimensional ultrasound imaging. Sarcopenic levels of muscle mass were defined by established criteria (1, appendicular skeletal muscle mass [ASM]; 2, ASM/height2 ; and 3, ASM/body mass index) based on the ASM and total muscle mass measured by a bioelectrical impedance analysis. The discriminative power of RF-CSA was assessed by receiver operating characteristic curves, and optimal cutoffs were determined by the maximum Youden index (J). RESULTS: One hundred thirteen patients with CKD (mean age [SD], 62.0 [14.1] years; 48% male; estimated glomerular filtration rate, 38.0 [21.5] mL/min/1.73m2 ) were included. The RF-CSA was a moderate predictor of ASM (R2 = 0.426; P < .001) and total muscle mass (R2 = 0.438; P < .001). With a maximum J of 0.47, in male patients, an RF-CSA cutoff of less than 8.9 cm2 was deemed an appropriate cutoff for detecting sarcopenic muscle mass. In female patients, an RF-CSA cutoff of less than 5.7 cm2 was calculated on the basis of ASM/height2 (J = 0.71). CONCLUSIONS: Ultrasound may provide a low-cost and simple means to diagnose sarcopenia in patients with CKD. This would allow for early management and timely intervention to help mitigate the effects in this group.

Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min-1·1.73 m-2 (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min-1·1.73 m-2, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min-1·1.73 m-2) completed 20 min of walking at 60-70% peak O2 consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (P = 0.001) and nonclassical (P = 0.002) monocyte subset proportions but decreased the intermediate subset (P < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups (P = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).

Identification of the most clinically useful skeletal muscle mass indices pertinent to sarcopenia and physical performance in chronic kidney disease.

AIM: Patients with chronic kidney disease (CKD) are characterised by low skeletal muscle mass that negatively impacts physical performance. Operational definitions of 'low muscle mass' are inconsistent, and it is unknown how different skeletal muscle mass indices affect the relationship between muscle mass and physical function. METHODS: Appendicular skeletal muscle mass (ASM) was measured by dual-energy X-ray absorptiometry in 72 CKD patients. Along with crude ASM, alternative muscle indices were calculated adjusting for height, height-squared, body mass, and BMI. Physical performance was assessed by handgrip strength, sit-to-stand tests, gait speed, the incremental shuttle walk test and 'Short Physical Performance Battery'. RESULTS: Prevalence of 'low muscle mass' ranged from 26% to 35% of patients depending on the criteria used. The relationship between muscle mass indices and physical function differed for each criteria. Using average coefficients, the association with overall physical function and muscle indices were as follows: crude ASM (r = .258), ASM/height (r = .249), ASM/height-squared (r = .332), ASM/body mass (r = .249) and ASM/BMI (r = .206). Muscle adjusted for markers of adiposity (ASM/body fat %, r = .266; ASM/fat mass, r = .338) provided the best overall associations with physical function. CONCLUSION: The use of alternative muscle mass indices provide different estimates of 'low muscle mass' prevalence, and the strongest (and most useful definition in regard to functional status) involves adjustment for either total or relative body fat. ASM adjusted for adiposity may be physiologically and clinically more relevant in patients with renal disease.

Postural stability during standing and its association with physical and cognitive functions in non-dialysis chronic kidney disease patients.

PURPOSE: Chronic kidney disease (CKD) is characterised by poor physical function. A possible factor may be aberrant changes to balance and postural stability (i.e. ability to maintain centre of pressure (COP)). Previous research has exclusively focused on patients undergoing renal replacement therapy (RRT). The current study investigated postural stability in a group of CKD patients not requiring RRT. METHODS: 30 CKD patients (aged 57.0 ± 17.8 years, 47% female, mean eGFR 42.9 ± 27.2 ml/kg/1.73 m2) underwent a series of physical function assessments including the sit-to-stand-5 and -60, incremental shuttle walk test, gait speed, and short physical performance battery. Postural stability (defined as total COP ellipse (mm2) displacement) was measured using the Fysiometer board. Control reference data were provided by the manufacture. Cognitive function was assessed using the 'Montreal Cognitive Assessment-Basic' (MOCA-B)'. RESULTS: CKD patients had poorer postural stability during quiet standing than reference values across all age categories (≤ 39 years, 24.9 ± 11.3 vs. 10.4 ± 1.8 mm2; 40-59 years, 34.3 ± 19.0 vs. 17.7 ± 6.2 mm2; ≥ 60 years, 39.7 ± 21.2 vs. 16.8 ± 2.9 mm2, all comparisons P < 0.001). Reductions in postural stability were associated with both physical and cognitive functioning. In females only, postural stability worsened with declining renal function (r = - 0.790, P < 0.01). CONCLUSIONS: To our knowledge, this is the first and largest experimental report concerning measurement of postural stability of CKD patients not requiring RRT. Our findings suggest that postural stability is associated with worse physical and cognitive functioning in this patient group.

Anthropometry-based Equations to Estimate Body Composition: A Suitable Alternative in Renal Transplant Recipients and Patients With Nondialysis Dependent Kidney Disease?

OBJECTIVE: Chronic kidney disease (CKD) patients and renal transplant recipients (RTRs) are characterized by aberrant body composition such as muscle wasting and obesity. It is still unknown which is the most accurate method to estimate body composition in CKD. We investigated the validity of the Hume equation and bioelectrical impedance analysis (BIA) as an estimate of body composition against dual-energy X-ray absorptiometry (DXA) in a cohort of nondialysis dependent (NDD)-CKD and RTRs. DESIGN AND METHODS: This was a cross-sectional study with agreement analysis of different assessments of body composition conducted in 61 patients (35 RTRs and 26 NDD-CKD) in a secondary care hospital setting in the UK. Body composition (lean mass [LM], fat mass [FM], and body fat% [BF%]) was assessed using multifrequency BIA and DXA, and estimated using the Hume formula. Method agreement was assessed by intraclass correlation coefficient (ICC), regression, and plotted by Bland and Altman analysis. RESULTS: Both BIA and the Hume formula were able to accurately estimate body composition against DXA. In both groups, the BIA overestimated LM (1.7-2.1 kg, ICC .980-.984) and underestimated FM (1.3-2.1 kg, ICC .967-.972) and BF% (3.1-3.8%, ICC .927-.954). The Hume formula also overestimated LM (3.5-3.6 kg, ICC .950-.960) and underestimated BF% (1.9-2.1%, ICC .808-.859). Hume-derived FM was almost identical to DXA in both groups (-0.3 to 0.1 kg, ICC .947-.960). CONCLUSION: Our results demonstrate, in RTR and NDD-CKD patients, that the Hume formula, whose estimation of body composition is based only upon height, body mass, age, and sex, may reliably predict the same parameters obtained by DXA. In addition, BIA also provided similar estimates versus DXA. Thus, the Hume formula and BIA could provide simple and inexpensive means to estimate body composition in renal disease.

Characterising skeletal muscle haemoglobin saturation during exercise using near-infrared spectroscopy in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients have reduced exercise capacity. Possible contributing factors may include impaired muscle O2 utilisation through reduced mitochondria number and/or function slowing the restoration of muscle ATP concentrations via oxidative phosphorylation. Using near-infrared spectroscopy (NIRS), we explored changes in skeletal muscle haemoglobin/myoglobin O2 saturation (SMO2%) during exercise. METHODS: 24 CKD patients [58.3 (± 16.5) years, eGFR 56.4 (± 22.3) ml/min/1.73 m2] completed the incremental shuttle walk test (ISWT) as a marker of exercise capacity. Using NIRS, SMO2% was measured continuously before, during, and after (recovery) exercise. Exploratory differences were investigated between exercise capacity tertiles in CKD, and compared with six healthy controls. RESULTS: We identified two discrete phases; a decline in SMO2% during incremental exercise, followed by rapid increase upon cessation (recovery). Compared to patients with low exercise capacity [distance walked during ISWT, 269.0 (± 35.9) m], patients with a higher exercise capacity [727.1 (± 38.1) m] took 45% longer to reach their minimum SMO2% (P = .038) and recovered (half-time recovery) 79% faster (P = .046). Compared to controls, CKD patients took significantly 56% longer to recover (i.e., restore SMO2% to baseline, full recovery) (P = .014). CONCLUSIONS: Using NIRS, we have determined for the first time in CKD, that favourable SMO2% kinetics (slower deoxygenation rate, quicker recovery) are associated with greater exercise capacity. These dysfunctional kinetics may indicate reduced mitochondria capacity to perform oxidative phosphorylation-a process essential for carrying out even simple activities of daily living. Accordingly, NIRS may provide a simple, low cost, and non-invasive means to evaluate muscle O2 kinetics in CKD.

Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is characterized by adverse changes in body composition, which are associated with poor clinical outcome and physical functioning. Whilst size is the key for muscle functioning, changes in muscle quality specifically increase in intramuscular fat infiltration (myosteatosis) and fibrosis (myofibrosis) may be important. We investigated the role of muscle quality and size on physical performance in non-dialysis CKD patients. METHODS: Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality was assessed using echo intensity (EI), and qualitatively using Heckmatt's visual rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA). Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental (ISWT) and endurance shuttle walk tests, lower limb and handgrip strength, exercise capacity (VO2peak) and gait speed. RESULTS: A total of 61 patients (58.5 ± 14.9 years, 46% female, estimated glomerular filtration rate 31.1 ± 20.2 mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was significantly associated with better physical performance [STS-60 (r = 0.363) and ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was closely associated with EI values, and significant differences in function were seen between the ratings. RF-CSA was a better predictor of performance than muscle quality. CONCLUSIONS: In CKD, increased US-derived EI was negatively correlated with physical performance; however, muscle size remains the largest predictor of physical function. Therefore, in addition to the loss of muscle size, muscle quality should be considered an important factor that may contribute to deficits in mobility and function in CKD. Interventions such as exercise could improve both of these factors.

Do stiffness and asymmetries predict change of direction performance?

Change of direction speed (CODS) underpins performance in a wide range of sports but little is known about how stiffness and asymmetries affect CODS. Eighteen healthy males performed unilateral drop jumps to determine vertical, ankle, knee and hip stiffness, and a CODS test to evaluate left and right leg cutting performance during which ground reaction force data were sampled. A step-wise regression analysis was performed to ascertain the determinants of CODS time. A two-variable regression model explained 63% (R2 = 0.63; P = 0.001) of CODS performance. The model included the mean vertical stiffness and jump height asymmetry determined during the drop jump. Faster athletes (n = 9) exhibited greater vertical stiffness (F = 12.40; P = 0.001) and less asymmetry in drop jump height (F = 6.02; P = 0.026) than slower athletes (n  = 9); effect sizes were both "large" in magnitude. Results suggest that overall vertical stiffness and drop jump height asymmetry are the strongest predictors of CODS in a healthy, non-athletic population.