Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Associations between bioelectrical impedance analysis-derived phase angle, protein-energy wasting and all-cause mortality in older patients undergoing haemodialysis.

AIM: Protein-energy wasting (PEW) is a common syndrome in patients undergoing haemodialysis (HD) and is associated with poor prognosis. Bioelectrical impedance analysis (BIA)-derived phase angle (PA) is useful for predicting PEW, but sex and age need to be considered. We aimed to reveal sex-specific cut-off values of PA predicting PEW in HD patients aged ≥65. METHODS: This two-centre retrospective cohort study included patients on HD who underwent BIA. PEW was detected using the International Society of Renal Nutrition and Metabolism (ISRNM) criteria as a reference. The PA was measured using a multifrequency bioimpedance device. Sex-specific cut-off values of PA predicting PEW were detected by receiver-operator characteristic analysis. We investigated the association between PEW determined using sex-specific cut-off values for PA and all-cause mortality. RESULTS: This study included 274 patients undergoing HD, with a median age of 75 (70-80) years, mean PA of 3.8 ± 1.1° and PEW of 43%. Over a median follow-up duration of 1095 (400-1095) days, 111 patients died. Cut-off values of PA predicting PEW were as follows: female, 3.00° (sensitivity, 87.3%; specificity, 77.5%), and male, 3.84° (sensitivity, 77.6%; specificity, 71.4%). The kappa coefficient between sex-specific cut-off values of the PA and ISRNM criteria had a moderate coincidence level of 0.55. PEW detected by PA was independently associated with all-cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.51-3.85; p < .001). CONCLUSIONS: Sex-specific cut-off values for PA in older HD patients may be useful as a screening tool for predicting PEW and mortality.

Comparison of intradialytic continuous and interval training on hemodynamics and dialysis adequacy: A crossover randomized controlled trial.

AIM: Circulating blood volume (BV) during exercise changes depending on the intensity and duration, and post-exercise hypotension is observed after continuous exercise. We investigated the safety and efficacy of both interval and continuous IDE at anaerobic threshold (AT) levels with respect to hemodynamic stability and dialysis efficiency. METHODS: In this crossover randomized controlled trial, 16 patients on haemodialysis were subjected to three trial arms, including non-IDE, interval-IDE, and continuous-IDE arms. Systolic blood pressure (SBP), BV, and ultraviolet absorbance - an indicator of dialysis efficiency - were continuously measured, and each change was compared between the three arms by two-way analysis of variance. RESULTS: Continuous IDE decreased SBP from post-exercise to the end of dialysis compared with baseline (pre 142.8 ± 19.0 vs. post 127.5 ± 24.5 mmHg, p = .02), whereas interval IDE maintained better SBP levels post-exercise (pre 139.9 ± 17.1 vs. post 140.1 ± 15.8 mmHg, p = 1.0) than continuous IDE (non-IDE 133.2 ± 19.9 vs. interval 140.1 ± 15.8 vs. continuous 127.5 ± 24.5 mmHg, p = .04). Moreover, interval IDE caused less tiredness and few symptoms (p < .05), despite reaching higher intensity than continuous IDE (p = .001). The BV of each IDE arm decreased during exercise and recovered post-exercise to the same level as non-IDE. Ultraviolet absorbance was not different between each arm (p = .16). CONCLUSION: AT-level interval IDE maintains better hemodynamic stability from post-exercise to the end of dialysis and may represent a novel approach that can be effectively performed with fewer symptoms.

Association of Postexercise Vagal Dysfunction With Protein-Energy Wasting and Noncardiovascular Outcomes in Patients Receiving Hemodialysis: A Retrospective Cohort Study.

OBJECTIVE: Postexercise vagal dysfunction is linked to noncardiovascular mortality in hemodialysis patients, but the mechanism is unknown. This study aimed to determine the association of cardiovagal neuropathy with systemic inflammation, protein-energy wasting, and noncardiovascular hospitalization. METHODS: This 2-center retrospective cohort study analyzed data from 280 hemodialysis patients who underwent exercise test. Patients were assessed for heart rate (HR) recovery (bpm) for 1 minute after exercise, a marker of vagal function, and were divided into 3 categories (Low: ≤ 6, Mid: 7-11, High: ≥ 12 bpm). We followed 1-year changes in the systemic inflammation-based prognostic score (Glasgow Prognostic Score [GPS]), body weight, and creatinine generation rate (CGR), an indicator of muscle mass, as well as 2-year hospitalization. RESULTS: The HR recovery category was associated with serum C-reactive protein and albumin levels and GPS. After 1 year, the low HR recovery category was associated with worsening in GPS (low, 0 [0-0.5]; mid, 0 [0-1]; high, 0 [0-0]), weight (low, 100.0 [96.1-102.5]; mid, 101.3 [98.9-105.0]; high, 100.5 [98.2-102.9]%), and CGR (low, 97.0 [88.5-111.4]; mid, 110.2 [90.9-124.8]; high, 106.2 [95.5-115.5]%), and the correlations with GPS and CGR remained consistent after adjusting for confounders such as exercise capacity and hospitalization during the follow-up period. There were 117 patients hospitalized. Compared to the high HR recovery category, the mid (hazard ratio: 1.8, 95% confidence interval [CI]: 1.1-3.1, P = .02) and low (hazard ratio: 2.4, 95% CI: 1.5-4.0, P = .001) categories were independently associated with an increased risk of all-cause hospitalization. For noncardiovascular disease hospitalization, the low HR recovery category was independently associated with increased risk of hospitalization (hazard ratio: 2.1, 95% CI: 1.2-3.7, P = .007). CONCLUSIONS: Vagal neuropathy in this population can contribute to adverse outcomes associated with systemic inflammation and protein-energy wasting.

Association of cardiac autonomic neuropathy assessed by heart rate response during exercise with intradialytic hypotension and mortality in hemodialysis patients.

The heart rate (HR) reflects the dynamic behavior of the autonomic nervous system, and HR profiles during the exercise test provide prognostic information. However, there are no reports of these factors in hemodialysis patients. Data from 256 patients (mean 68.8 years old) who underwent an exercise test were statistically analyzed. Patients were evaluated for the percent HR reserve from HR at peak exercise, HR recovery for one minute after peak exercise, and exercise capacity, as well as intradialytic hypotension (IDH). The prevalence of chronotropic incompetence (96.1%), defined as under 80% HR reserve, and abnormal HR recovery (60.5%), defined as under 12 beats, were very common. Eighty-four deaths occurred during the follow-up period (median, 3.8 years). A slow HR recovery under 7 beats was associated with IDH after adjustment (odds ratio 2.7, 95% confidence interval 1.1-6.4). HR recovery under 12 beats (hazard ratio over study period 5.1, 95% confidence interval 2.5-10.5), HR reserve under 26.2% (3.4, 1.7-6.8), and IDH (1.7, 1.1-2.8) were associated with all-cause mortality after adjustment. Considering the confounding of all three variables, only HR recovery under 12 beats remained associated with the all-cause and cause-specific mortality ("cardiovascular" and "non-cardiovascular"). This association was consistent even in subgroup analyses based on the presence of diabetes and cardiovascular disease. Thus, HR profiles during the exercise can reflect potential health conditions related to cardiac autonomic neuropathy in hemodialysis patients that affect IDH and their survival.

An equation to predict peak heart rate for prescribing exercise intensity in middle-aged to older patients requiring hemodialysis.

PURPOSE: Exercise prescription based on a population-specific physiological response can help ensure safe and effective physical interventions. However, as a facile approach for exercise prescription in hemodialysis population that is based on their exercise capacity has not yet been established, the aim of our study was to develop a unique prediction formula for peak heart rate (HR) that can be used in this population. METHODS: This cross-sectional study measured physical function and HR at peak exercise and anaerobic threshold (AT) during cardiopulmonary exercise tests in 126 individuals. Participants were randomly assigned to the development group (n = 78), whose data were used to calculate the prediction equation, or the validation group (n = 48). RESULTS: The HR reserve in this population was significantly lower (0.44 ± 0.20%) and there was a large discrepancy between conventional age-predicted maximal HR and measured peak-HR values (R = 0.36). The average of the ratio between HR at AT point and peak HR was 85% (95% CI, 83.5%-86.4%). The peak-HR prediction equation was based on resting HR, presence of diabetes, physical dysfunction (gait speed < 1.0 m/s), and hypoalbuminemia (< 3.5 g/dL). It showed high prediction accuracy (R2 [95%CI] = 0.71 [0.70-0.71]) with similar correlation coefficients between the development and validation groups (R = 0.82). CONCLUSION: Aerobic exercise based on estimated peak HR < 85% obtained from the equation in this study may enable safe and effective physical intervention in this population.

Relationship Among Falls, Fear of Falling, and Physical Activity Level in Patients on Hemodialysis.

OBJECTIVE: Patients on hemodialysis are highly susceptible to falls and fractures. Amplified apprehension regarding the fear of falling (FOF) constitutes a risk factor that restricts physical activity and escalates the probability of falls among the elderly population. This study aimed to elucidate the association between falls and FOF and physical activity in patients on hemodialysis. METHODS: A prospective cohort study was conducted across 9 centers. FOF was assessed using the Falls Efficacy Scale-International (FES-I). Physical activity was assessed using the Japanese version of the International Physical Activity Questionnaire short form. Subsequently, falls were monitored over a duration of 1 year. Logistic regression analysis was performed to evaluate the relationship between falls and FOF and physical activity. In addition, in the receiver operating characteristic analysis, the cutoff value of FES-I that predicts falls was determined using the Youden Index. A restricted cubic spline curve was utilized to analyze the nonlinear association between falls and the FES-I. RESULTS: A total of 253 patients on hemodialysis (70.0 [59.0-77.0] years old; 105 female [41.5%]) were included in the analysis. During the 1-year observation period, 90 (35.6%) patients experienced accidental falls. The median FES-I score was 36.0 (24.0-47.0) points, and patients with higher FES-I scores had more falls. Following adjusted logistic regression analysis, FES-I exhibited an independent association with falls (OR = 1.04; 95% CI = 1.01-1.06), but physical activity was not. The area under the receiver operating characteristic curve was 0.70 (95% CI = 0.64-0.77), and the FES-I threshold value for distinguishing fallers from non-fallers was determined as 37.5 points (sensitivity 65.6%, specificity 35.0%). A nonlinear relationship between falls and FES-I was observed. CONCLUSION: FOF was associated with the incidence of falls in patients on hemodialysis. IMPACT: The evaluation and implementation of interventions targeting the FOF may mitigate the risk of falls.

Relationships between frailty and exercise capacity in patients undergoing hemodialysis: A cross-sectional study.

AIM: Hemodialysis (HD) patients have a high prevalence of frailty. The association between frailty and exercise capacity in HD patients has not been established. This study aimed to clarify the relationships between frailty and exercise capacity in HD patients. METHODS: This two-center cross-sectional study included HD patients who performed cardiopulmonary exercise testing. Participants were divided by frailty phenotype into robust, pre-frail, and frail using the revised Japanese version of the Cardiovascular Health Study criteria. Peak oxygen uptake (peakVO2 ) measured by cardiopulmonary exercise testing was compared with each frailty phenotype. The association between peakVO2 and frailty phenotype was analyzed using multivariate linear regression analysis adjusted for age, sex, body mass index diabetes mellitus, cardiovascular disease, cancer, history of fracture, hemoglobin, left ventricle ejection fraction, and percentage of heart rate reserve. RESULTS: The study included 136 patients (median age, 71.0 years; female, 23.5%), with 15.4%, 44.9%, and 39.7% with frailty phenotypes robust, pre-frail, and frail, respectively. PeakVO2 decreased with deterioration of the frailty phenotype (robust, median 15.1 [13.7-18.3] mL/min/kg; pre-frail, median 12.2 [10.5-14.4] mL/min/kg; frail, median 10.6 [9.2-12.5] mL/min/kg, P < 0.05). PeakVO2 decline was significantly associated with frail (B = -2.19, P = 0.004). Modeling individual frailty components showed a significant association between peakVO2 , usual gait speed (B = 2.38, P = 0.04), and low physical activity (B = -1.44, P = 0.004). CONCLUSION: Frailty in HD patients was associated with a decline in exercise capacity. HD patients with frailty need to improve exercise capacity, gait speed, and physical activity. Geriatr Gerontol Int 2023; 23: 795-802.

Impact of the COVID-19 pandemic on exercise tolerance and patient outcomes with Phase III cardiac rehabilitation in Japan: A multicenter study.

This study aimed to determine how behavioural restrictions due to the emergency declaration following the coronavirus disease 2019 (COVID-19) pandemic affect exercise tolerance and its outcomes in patients in Phase III cardiac rehabilitation programme. This is a multicenter retrospective cohort study. Participants in outpatient cardiac rehabilitation programmes and cardiopulmonary exercise testing before and after the emergency declarations were included. A total of 90 participants were included (median age 75.0 years, 69% male), and the changes in physical function and exercise tolerance were compared before and after the emergency declaration. Patients were divided into a decline-in-peak oxygen uptake (VO2 ) group and a nondecline-in-peak VO2 group. Comparison before and after the emergency declaration showed that the anaerobic threshold declined significantly and peak VO2 exhibited a downward trend. The decline-in-peak VO2 group consisted of 16 patients (17%) with better exercise tolerance, multiple comorbidities, and declined lower extremity muscle strength. These patients also had a higher rate of subsequent composite events (hazard ratio, 5.2; 95% confidence interval, 1.4-18.8, p = 0.01). Before and after the emergency declaration, the patient's exercise tolerance may decline, leading to a poor prognosis. This study suggests the importance of maintaining exercise tolerance during the COVID-19 pandemic.

Characteristics and Related Factors of One-year Transition in Exercise Tolerance Following an Emergency Declaration due to the Coronavirus Disease 2019 Pandemic in Patients on Phase III Cardiac Rehabilitation.

OBJECTIVE: This study aimed to understand the long-term transition of exercise tolerance in patients on phase III cardiac rehabilitation (CR) and clarify the characteristics of patients with a high risk of declined exercise tolerance during the first emergency declaration. METHODS: Patients who participated in phase III outpatient CR before the first emergency declaration and those who performed cardiopulmonary exercise testing were at ≥2-time points: before and at 3 or 12 months post-emergency declaration. Exercise tolerance transition at 3-time points was analyzed, and whether different social background factors affected the peak oxygen uptake (V̇O2) transition method remains to be examined. RESULTS: A total of 101 (median age 74.0 years, 69% men), and both peak V̇O2 and anaerobic threshold (AT) significantly declined from pre-declaration to 3 months post-declaration but recovered to levels likely similar from pre-declaration at 12 months (peak V̇O2: from 17.3 to 16.7 to 18.7 mL/min/kg; AT: from 11.8 to 11.2 to 11.6 mL/min/kg). Further, patients with multiple comorbidities at pre-declaration had a significantly lower peak V̇O2 at 3 months (-1.0 mL/min/kg, p = 0.025) and it remained significantly low in those with a slower gait speed at 12 months after lifting the emergency declaration (-2.5 mL/min/kg, p = 0.009). CONCLUSION: The emergency declaration declined the exercise tolerance in patients on phase III CR but improved to pre- declaration levels over time, but more likely declined in patients with multiple comorbidities during pre-declaration and those with low-gait speeds were less likely to improve their declined exercise tolerance.

Temporal changes in cortical oxygenation in the motor-related areas and bilateral prefrontal cortex based on exercise intensity and respiratory metabolism during incremental exercise in male subjects: A near-Infrared spectroscopy study.

A recent study has reported that prefrontal cortex (PFC) activity during incremental exercise may be related to exercise termination on exhaustion. However, few studies have focused on motor-related areas during incremental exercise. This study investigated changes in the oxygenation of the PFC and motor-related areas using near-infrared spectroscopy during incremental exercise. Moreover, we analyzed the effect of exercise termination on changes in cortical oxygenation based on exercise intensity and respiratory metabolism. Sixteen healthy young male patients participated in this study. After a 4-min rest and 4-min warm-up period, incremental exercise was started at an incremental load corresponding to 20 W/min. Oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), and total hemoglobin (THb) in the bilateral PFC, supplementary motor area, and primary motor cortex were measured. We evaluated changes in oxygenation in each cortex before and after the anaerobic threshold (AT) and respiratory compensation point to identify changes due to respiratory metabolism. O2Hb and THb increased from moderate intensity or after AT to maximal exercise, and HHb increased slowly compared to O2Hb and THb; these changes in hemoglobin levels were consistent in all cortical areas we measured. However, the increase in each hemoglobin level in the bilateral PFC during incremental exercise was faster than that in motor-related areas. Moreover, changes in cortical oxygenation in the right PFC were faster than those in the left PFC. These results suggest changes based on differences in neural activity due to the cortical area.

Effect of blood volume change related to intensity of intradialytic aerobic exercise on hemodialysis adequacy: a pilot study.

PURPOSE: Intradialytic exercise may improve dialysis efficiency; however, the association between changes in blood volume (BV) related to exercise intensity and solute removal kinetics remains unknown. We herein investigated the relationship between changes in BV with exercise and removal of solute molecules during hemodialysis. METHODS: Each of the 21 hemodialysis patients underwent cardiopulmonary exercise test to measure anaerobic threshold (AT). According to the exercise intensity, patients were classified into two groups, the low group (n = 12), whose intensity was below the AT, and the high group (n = 9), whose intensity was at the AT level. Each patient completed two trial arms of resting and discontinuous exercise dialysis sessions in a randomized manner. RESULTS: The change in BV with the exercise dialysis session in the high group decreased during exercise (p = 0.028) and remained decreased after exercise (p = 0.016), compared with the low group. In the low group, compared with routine sessions, the removal of potassium (p = 0.030), phosphate (p = 0.024), and urea nitrogen (p = 0.065) increased during exercise, but the total removal of these solutes did not change. In the high group, the removal of phosphate (p < 0.001) and urea nitrogen (p = 0.018) after exercise and even total phosphate (p = 0.027) decreased. CONCLUSION: These findings suggest that the removal of small solute molecules is improved during exercise in intradialytic low-intensity exercise with no change in BV, and decreased after exercise in high-intensity exercise with a decrease in BV. CLINICAL TRIALS REGISTRY: Trial retrospectively registered at the UMIN Clinical Trials Registry: study number UMIN000038629 (Registration date: September 7, 2019).

Association between social frailty as well as early physical dysfunction and exercise intolerance among older patients receiving hemodialysis.

BACKGROUND: Recently, social frailty has been increasingly recognized as a factor associated with adverse health outcomes, including physical disability and mortality. However, there are no studies about the importance of this factor among hemodialysis patients. Therefore, we investigated the relationship between social frailty and early physical dysfunction in this group of patients. METHODS: This was a two-center cross-sectional study. Older patients receiving hemodialysis were prospectively enrolled. Moreover, participants were evaluated for social frailty based on the definition of previous study and for physical function, peak oxygen uptake (peak VO2 ), ventilatory equivalent for carbon dioxide (VE/VCO2 ) slope and heart rate reserve. Then, they were divided into two groups based on the presence of physical frailty. RESULTS: Data collected from 158 individuals were statistically analyzed. The prevalence rate of social frailty was 59.5%. In the non-physical frailty group, social frailty was found to be independently associated with reduced gait speed (P = 0.007), leg strength (P = 0.040) and peak VO2 (P = 0.023), but not with hand grip strength (P = 0.36). In the physical frailty group, there was no association between social frailty and physical function. Moreover, in patients without physical and social frailty, physical function was maintained at above accepted threshold levels, whereas peak VO2 (14.1 ± 3.3 mL/kg/min), VE/VCO2 slope (32.3 ± 5.5) and heart rate reserve (50.8% ± 21.7%) were substantially impaired. CONCLUSIONS: Patients receiving hemodialysis can present with social frailty and exercise intolerance with cardiac dysfunction in the early phase, which may contribute to subsequent dysfunction. Geriatr Gerontol Int 2021; 21: 664-669.