FRAILTY, CARDIOVASCULAR FUNCTION AND RISK OF FALLING AMONGST PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HAEMODIALYSIS

This PhD thesis explores the risk of falling of stage 5 chronic kidney disease (CKD-5) patients receiving haemodialysis (HD) therapy. Previous research has suggested that multiple risk factors such as older age, comorbidities, polypharmacy, and frailty contribute primarily to the increased risk of falling in this clinical population. However, HD patients are also characterised by severe cardiovascular disease burden that often manifests with symptoms of orthostatic intolerance, impaired blood pressure control and syncope, all of which may be implicated in the aetiology of falling. The aim of this thesis was to address important research questions, such as: Are frailty and its physical function/activity components associated with falling in CKD-5 patients on HD? Are baroreflex function and the cardiovascular responses to orthostasis also associated with falling? What is the relative importance of frailty and cardiovascular function as potential exercise-modifiable risk factors for falls in this patient group? A prospective observational study involving 76 prevalent HD patients (61.1±14 years) confirmed previous observations that CKD-5 patients on HD are at higher risk of falls compared to the non-uraemic population, as 37.7% of research participants experienced at least one fall during a 12-month follow-up, and the incidence of falls recorded was 1.16 falls/person-year. Although participants classified as fallers did not appear to differ from non-fallers in single physical function measures such as timed-up and go (TUG), 5 repetitions chair sit to stands (CSTS-5), or muscle strength, frailty and lower postural balance were associated with increased odds of falling. In addition, baroreflex function indices reflecting frequency of baroreflex activation, as well as the blood pressure response to a five-minute 60° head-up tilt test (HUT-60°) were associated with increased odds of falling and a greater number of falls. More importantly, we showed that modelling the risk of falling by adding a cardiovascular function variable to a frailty-only model improved significantly the prediction of number of falls experienced by CKD-5 patients on HD. Overall, this PhD thesis revealed that cardiovascular mechanisms implicated in the short-term regulation of blood pressure showed a greater relative importance than frailty in predicting falls in the study participants. These findings challenge the current assumption that frailty is the primary factor involved in the aetiology of falls in CKD-5 patients on HD. The clinical implications of this novel observation are also discussed from a preventive and rehabilitative perspective. Key words: Stage 5 chronic kidney disease, haemodialysis, falls, frailty, cardiovascular function

Validity and reliability of high-resolution ultrasound imaging for the assessment of regional body composition in stage 5 chronic kidney disease patients undergoing continuous ambulatory peritoneal dialysis

Tom Mercer - ORCID: 0000-0002-5078-4769 https://orcid.org/0000-0002-5078-4769Tobia Zanotto - ORCID 0000-0002-6571-4763 https://orcid.org/0000-0002-6571-4763Background: Accurate measurement of muscle mass is an important research and clinical tool. High-resolution ultrasound (US) has shown potential as a method to assess muscle and fat mass at specific anatomical sites. However, there is limited evidence for the reliability of US to measure muscle size in patients receiving continuous ambulatory peritoneal dialysis (CAPD). Therefore, we examined the validity and reliability of an US method compared to a gold standard comparison for the assessment of a quadriceps muscle in this clinical population. Methods: Twenty people receiving CAPD (mean age = 56.5 ± 16.7 years) at a single dialysis unit were assessed on two occasions, 7 days apart. Measures of the mid-thigh, such as vastus lateralis (VL) anatomical cross-sectional area (ACSA), VL muscle thickness and subcutaneous fat thickness were compared for US reliability and validity compared to magnetic resonance imaging (MRI) measures. Results: US had high validity against gold standard MRI measures, with intraclass correlation coefficients (ICC) equating to VL ACSA of 0.95, VL thickness of 0.99 and fat thickness of 0.98. The US measurements also exhibited high intra-rater reliability (ICCs: VL thickness = 0.98, total muscle thickness = 0.97 and fat thickness = 0.99) in measuring body composition at the mid-VL site in the study population. Conclusions: Valid assessment of regional body composition can be achieved via high-resolution US in patients receiving CAPD. The validity and reliability of the US in repeated measures (in comparison to the gold standard MRI) warrant further investigation in the wider chronic kidney disease population.42pubpub

Minimum accelerometer wear-time for reliable estimates of physical activity and sedentary behaviour of people receiving haemodialysis

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-31, accepted 2020-06-01, registration 2020-06-01, online 2020-06-16, epub 2020-06-16, collection 2020-12Background: Low levels of physical activity are implicated in low life expectancies of people receiving maintenance haemodialysis. Accelerometers are increasingly being used to quantify activity behaviours of this population but guidance to quality-assure such data is lacking. The objective of this study was to provide data processing and reduction recommendations to ensure accelerometer-derived outcomes are sufficiently reliable for interpretative analysis. Methods: Seventy people receiving maintenance haemodialysis (age 55.9 ± 15.7 years, 34% women, 23% diabetic) from a single outpatient renal unit volunteered for the study. Participants wore Actigraph GT3x and ActivPAL monitors during waking hours over seven days. Reliability of accelerometer output (normalised to wear-time) was assessed via intraclass correlation coefficient (ICC). The Spearman-Brown prophecy formula was subsequently applied to the ICCs to derive the minimum required accelerometer wear-time for each behavioural outcome. Results: Monitor wear compliance was greater on dialysis compared to non-dialysis days (90% v 77%). Participants were significantly more active on non-dialysis days compared to dialysis days but there were no significant differences in estimated behaviours between days within the same condition. Average measure ICCs for all accelerometer outcomes were high (range 0.76–0.96). Computations indicated that habitual physical activity and sedentary behaviour could be estimated with a minimum reliability level of 0.80 from one dialysis day and two non-dialysis days, and at least eight hours monitor wear per day. Applying this rubric allowed 90% of participant data to be retained for further analysis. Conclusions: Regardless of accelerometer, one dialysis and two non-dialysis days data with a minimum of eight hours wear each day should enable habitual activity of people receiving maintenance haemodialysis to be characterised with acceptable reliability. These recommendations reconcile the tension between wear-time criteria stringency and retention of an adequately representative sample.21pubpu

Postural control data from prevalent kidney transplant patients with and without history of falls

From Elsevier via Jisc Publications RouterItem not available in this repository.This article presents data from a research paper entitled “Postural balance, muscle strength, and history of falls in end-stage renal disease patients living with a kidney transplant: a cross-sectional study” available in Journal Gait and Posture [1]. In this article, we reported the minimal detectable changes at the 95% level of confidence (MDC95) of postural balance variables measured in eyes open (EO) and eyes closed (EC) conditions, with a stabilometric platform, in 59 kidney transplant (KT) recipients (mean age= 53.2 ± 11 years). In addition, we also performed receiver operating characteristics (ROC) curve analysis to explore the ability of postural balance measures to discriminate fallers and non-fallers (history of falls: yes or no). Sensitivity, specificity and area under the curve (AUC) of mean center of pressure velocity (CoPv), sway area (SA), center of pressure range of displacement in the anterior-posterior (AP) and medio-lateral (ML) directions were calculated. These data can be used by researchers aiming to design psychometric studies of postural balance in KT patients and they also provide clinicians with information on possible prioritization of outcome assessment for future fall-risk research in this clinical population.31pubpu

Screening tools to expedite assessment of frailty in people receiving haemodialysis: A diagnostic accuracy study

From Springer Nature via Jisc Publications RouterAbstract: Background: Frailty is associated with multiple adverse outcomes in stage-5 chronic kidney disease (CKD-5) and upwards of one third of people receiving haemodialysis (HD) are frail. While many frailty screening methods are available in both uremic and non-uremic populations, their implementation in clinical settings is often challenged by time and resource constraints. In this study, we explored the diagnostic accuracy of time-efficient screening tools in people receiving HD. Methods: A convenience sample of 76 people receiving HD [mean age = 61.1 years (SD = 14), 53.9% male] from three Renal Units were recruited for this cross-sectional study. Frailty was diagnosed by means of the Fried phenotype. Physical performance-based screening tools encompassed handgrip strength, 15-ft gait speed, timed up and go (TUG), and five-repetition sit to stand (STS-5) tests. In addition, participants completed the SF-36 Health Survey, the short-form international physical activity questionnaire and the Tinetti falls efficacy scale (FES) as further frailty-related measures. Outcome measures included the area under the curve (AUC), sensitivity, specificity, positive (PPV) and negative predictive values (NPV). The diagnostic performance of screening tools in assessing fall-risk was also investigated. Results: Overall, 36.8% of participants were classified as frail. All the examined instruments could significantly discriminate frailty status in the study population. Gait speed [AUC = 0.89 (95%CI: 0.81–0.98), sensitivity = 75%, specificity = 93%] and TUG [AUC = 0.90 (95%CI: 0.80–0.99), sensitivity = 89%, specificity = 85%] exhibited the highest diagnostic accuracy. There was a significant difference in gait speed AUC (20%, p = 0.013) between participants aged 65 years or older (n = 36) and those under 65 years of age (n = 40), with better discriminating performance in the younger sub-group. The Tinetti FES was the only instrument showing good diagnostic accuracy (AUCs≥0.80) for both frailty (sensitivity = 82%, specificity = 79%) and fall-risk (sensitivity = 82%, specificity = 71%) screening. Conclusions: This cross-sectional study revealed that time- and cost-efficient walking performance measures can accurately be used for frailty-screening purposes in people receiving HD. While self-selected gait speed had an excellent performance in people under 65 years of age, TUG may be a more suitable screening method for elderly patients (≥65 years). The Tinetti FES may be a clinically useful test when physical testing is not achievable.This work was supported by a British Kidney Patient Association – British Renal Society joint grant (BKPA-BRS grant number: 16–003). The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.21pubpu

Effect of a multi-ingredient supplement on intermittent sprint performance, fatigue perception, muscle damage and immunosuppression in recreational athletes

Abstract not availabl

Use of a wearable accelerometer to evaluate physical frailty in people receiving haemodialysis

Thomas Mercer - ORCID: 0000-0002-5078-4769 https://orcid.org/0000-0002-5078-4769Marietta van der Linden - ORCID: 0000-0003-2256-6673 https://orcid.org/0000-0003-2256-6673Pelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Background Physical frailty is a major health concern among people receiving haemodialysis (HD) for stage-5 chronic kidney disease (CKD-5). Wearable accelerometers are increasingly being recommended to objectively monitor activity levels in CKD-5 and recent research suggests they may also represent an innovative strategy to evaluate physical frailty in vulnerable populations. However, no study has yet explored whether wearable accelerometers may be utilised to assess frailty in the context of CKD-5-HD. Therefore, we aimed to examine the diagnostic performance of a research-grade wearable accelerometer in evaluating physical frailty in people receiving HD. Methods Fifty-nine people receiving maintenance HD [age = 62.3 years (SD = 14.9), 40.7% female] participated in this cross-sectional study. Participants wore a uniaxial accelerometer (ActivPAL) for seven consecutive days and the following measures were recorded: total number of daily steps and sit-to-stand transitions, number of daily steps walked with cadence < 60 steps/min, 60–79 steps/min, 80–99 steps/min, 100–119 steps/min, and ≥ 120 steps/min. The Fried phenotype was used to evaluate physical frailty. Receiver operating characteristics (ROC) analyses were performed to examine the diagnostic accuracy of the accelerometer-derived measures in detecting physical frailty status. Results Participants classified as frail (n = 22, 37.3%) had a lower number of daily steps (2363 ± 1525 vs 3585 ± 1765, p = 0.009), daily sit-to-stand transitions (31.8 ± 10.3 vs 40.6 ± 12.1, p = 0.006), and lower number of steps walked with cadence of 100–119 steps/min (336 ± 486 vs 983 ± 797, p < 0.001) compared to their non-frail counterparts. In ROC analysis, the number of daily steps walked with cadence ≥ 100 steps/min exhibited the highest diagnostic performance (AUC = 0.80, 95% CI: 0.68–0.92, p < 0.001, cut-off ≤ 288 steps, sensitivity = 73%, specificity = 76%, PPV = 0.64, NPV = 0.82, accuracy = 75%) in detecting physical frailty. Conclusions This study provided initial evidence that a wearable accelerometer may be a useful tool in evaluating physical frailty in people receiving HD. While the total number of daily steps and sit-to-stand transitions could significantly discriminate frailty status, the number of daily steps walked with cadences reflecting moderate to vigorous intensity of walking may be more useful in monitoring physical frailty in people receiving HD.This work was supported by a British Kidney Patient Association – British Renal Society (BKPA—BRS) joint grant (grant number: 16–003) and by a Queen Margaret University PhD bursary. The funders of this study had no role in the study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.https://doi.org/10.1186/s12882-023-03143-zpubpu

Resistance Exercise in People With Stage-3 Chronic Kidney Disease: Effects of Training Frequency (Weekly Volume) on Measures of Muscle Wasting and Function

From Frontiers via Jisc Publications RouterHistory: collection 2022, received 2022-04-06, accepted 2022-06-09, epub 2022-06-24Publication status: PublishedBackground: Resistance training (RT) is a proven anabolic intervention in people living with and without chronic kidney disease (CKD). To date, there is a dearth of knowledge regarding the dose-response relationship of RT in the non-dialysis dependent CKD population. Therefore, we aimed to explore the effects of RT frequency (weekly volume) on established measures of muscle wasting and function in CKD. Methods: Twenty people with stage-3 CKD (CKD-3) were allocated to either a low frequency (one-session per week, RT1) or higher frequency (three-sessions per week, RT3) 12-week RT programme consisting of lower extremity strengthening exercises. The two RT programmes were not volume matched. Assessment outcomes before and after the intervention included measures of total and regional body composition, muscle size and architecture, strength, physical function, and uraemic symptoms. Results: Significant improvements over time in muscle size and architecture, strength, physical function, and uraemic symptoms were observed for both RT1 and RT3. Compared to RT1, participants who performed RT3 showed greater increases in vastus lateralis (VL) anatomical cross-sectional area (30.8% vs. 13.2%, p < 0.001) and pennation angle (36.3% vs. 17.5%, p = 0.008) after 12 weeks. In either group, there were no significant changes over time in mid-VL fascicle length, nor in measures of total body composition and upper arm muscle strength. Conclusion: Despite the group differences observed in the VL physiological adaptations, the strength and physical function responses, as well as the reductions of uraemic symptoms, were similar whether training once or thrice weekly. Therefore, performing RT just once per week may be an effective pre-habilitation strategy for people with CKD-3

The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: A prospective cohort study

From PubMed via Jisc Publications RouterTobia Zanotto - ORCID 0000-0002-6571-4763 https://orcid.org/0000-0002-6571-4763Marietta van der Linden - ORCID 000-0003-2256-6673 https://orcid.org/0000-0003-2256-6673Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients. Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up. In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p = 0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p = 0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants. This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms. ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).This work was supported by a British Kidney Patient Association – British Renal Society joint grant (BKPA-BRS grant number: 16–003). The funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.21pubpu

Baroreflex function, haemodynamic responses to an orthostatic challenge, and falls in haemodialysis patients

From PLOS via Jisc Publications Router.History: collection 2018, received 2018-05-24, accepted 2018-11-12, epub 2018-12-06Publication status: PublishedBackground Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients. Methods Seventy-six HD patients were enrolled in this cross-sectional study. Participants were classified as “fallers” and “non-fallers” and completed a passive head up tilting to 60o (HUT-60°) test on an automated tilt table. ECG signals, continuous and oscillometric BP measurements and impedance cardiography were recorded. The following variables were derived from these measurements: heart rate (HR) stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), number of baroreceptor events, and baroreceptor effectiveness index (BEI). Results The forty-four participants who were classified as fallers (57.9%) had a lower number of baroreceptor events (6.5±8.5 vs 14±16.7, p = .027) and BEI (20.8±24.2% vs 33.4±23.3%, p = .025). In addition, fallers experienced a significantly larger drop in systolic (-6.4±10.9 vs -0.4±7.7 mmHg, p = .011) and diastolic (-2.7±7.3 vs 1.8±6 mmHg, p = .027) oscillometric BP from supine to HUT-60° compared with non-fallers. None of the variables taken for the analysis were significantly associated with falls in multivariate logistic regression analysis. Conclusions This cross-sectional comparison indicates that, at rest, HD patients with a positive history of falls present with a lower count of baroreceptor sequences and BEI. Short-term BP regulation warrants further investigation as BP drops during a passive orthostatic challenge may be implicated in the aetiology of falls in HD