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The risk of virus transmission via the touching of contaminated masks has long been assumed by infection control teams. Yet, robust evidence to support this belief has been lacking. This risk was investigated in a laboratory setting by measuring the amount of viable influenza virus successfully transferred from artificially contaminated medical (surgical) mask surfaces to a human finger used to swipe their outer surface under various experimental conditions. Despite being exposed to high levels of virus contamination on the masks, very little or no viable virus was successfully transferred from the mask to the finger in these experiments.
Subject(s)
Influenza, Human , Masks , Humans , Masks/virology , Influenza, Human/transmission , Influenza, Human/prevention & control , Influenza, Human/virology , Touch , Equipment Contamination , OrthomyxoviridaeABSTRACT
Objective: The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. DESIGN: This study was a single- center pilot trial. SETTING: The study took place in the Faculty of Health, Tsukuba University of Technology, Japan. PARTICIPANTS: Hypertensive community-dwelling elderly people took part in the study. INTERVENTION: Microcirculation was observed before and 1 min after an arm-curl exercise by means of capillary microscopy of the non-exercised limb. Additionally, we examined other health-related indicators. Methods: We measured the acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters. Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3 ± 6.7 to 2.7 ± 0.2 log µm/s (p < 0.01), and the capillary density changed from 0.8 ± 0.2 to 0.9 ± 0.1 log/mm (p < 0.01), which included a significant increase in the non-exercising limb. Significant correlations were observed between the nailfold capillary diameter and body fat mass, the capillary diameter and physical activity, and the capillary density and bone mineral density. Conclusions: The acute effects of exercise on high-risk elderly individuals can be safe, and even 1 of min exercise can potentially improve their nailfold capillary function, despite the brief time, compared to no exercise. The results indicate that capillaries have an impact on the function of the whole body. Thus, they may be a useful diagnostic tool for assessing nailfold capillaries.
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Acute myocardial infarction (AMI) is associated with a decline in renal function. This study aimed to investigate the impact of engaging in moderate to vigorous intensity physical activity (MVPA) for more than 30 min per day on changes in renal function during the first 3 months after AMI onset. A prospective, observational study was conducted, enrolling 87 patients (75 men; average age, 65.2 ± 12.5 years) who had experienced AMI. The cystatin C-based estimated glomerular filtration rate (eGFRcys) was collected at and 3 months after discharge. Daily MVPA was measured using triaxial accelerometers at a threshold of 3.0 Metabolic equivalent of the task for 3 months. Generalized estimating equations (GEE) were applied to evaluate the longitudinal association between the number of days per week of MVPA for 30 min or more and within-patient changes in eGFRcys. The patients were categorized into three groups based on their MVPA engagement days: 0 days (n = 20), 1-2 days (n = 14), and 3-7 days (n = 53) groups. After adjusting for potential confounding variables, GEE analysis revealed that the eGFRcys slope over 3 months was significantly higher in the 3-7 days group than in 0 days group (B = 2.9, (95% confidence interval: 1.5-4.2), p < 0.001). Similar results were obtained when MVPA time thresholds were set to 40 and 60 min. These findings suggest a significant positive effect of engaging in MVPA for 30 min or more for 3-7 days per week in the improvement of renal function after AMI onset.
Subject(s)
Myocardial Infarction , Aged , Humans , Male , Middle Aged , Exercise , Glomerular Filtration Rate , Kidney , Myocardial Infarction/complications , Prospective Studies , FemaleABSTRACT
Chronic kidney disease (CKD) is a global health problem. In patients with CKD, exercise endurance is decreased, especially as renal dysfunction advances. This is due to the combined effects of protein-energy wasting, uremic acidosis, and inflammatory cachexia, which lead to sarcopenia and are aggravated by a sedentary lifestyle, resulting in a progressive downward spiral of deconditioning. Renal rehabilitation (RR) is a coordinated, multifaceted intervention designed to optimize a patient's physical, psychological, and social functioning, as well as to stabilize, slow, or even reverse the progression of renal deterioration, improving exercise tolerance and preventing the onset and worsening of heart failure, thereby reducing morbidity and mortality. This review focused on the history and benefits of RR in patients with CKD. Based on current evidence, RR is an effective, feasible, and safe secondary prevention strategy in CKD. RR is a promising model for a new field of rehabilitation. Therefore, efforts to increase RR implementation rates are urgently needed.
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Exercise training (Ex) has anti-hypertensive and renal protective effects. In this study, we investigate the effects of Ex on mitochondrial fatty acid metabolism in the kidneys of Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS) diet. Eight-week-old, male Dahl-S rats were divided into three groups: (1) normal-salt diet, sedentary (NS-Sed), (2) HS diet, sedentary (HS-Sed), and (3) HS-Ex. The NS and HS groups were fed a diet containing 0.6% and 8% NaCl, respectively. The HS-Ex group performed treadmill running for 8 weeks (5 days/week; 60 min/day at 16-20 m/min, 0% gradient). Renal function and the expression of enzymes and regulators of ß-oxidation and electron transport chain (ETC) complexes were assessed. HS increased systolic blood pressure and proteinuria, and Ex ameliorated these defects. HS also reduced creatinine clearance, and Ex ameliorated it. HS reduced the renal expression of enzymes of ß-oxidation (carnitine palmitoyltransferase type I (CPTI) and acyl-CoA dehydrogenases (CADs)) and the related transcription factors peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α), and Ex restored this. HS also reduced the renal expression of enzymes in ETC complexes, and Ex restored this expression. Ex ameliorates HS-induced renal damage by upregulating enzymes involved in fatty acid ß-oxidation and ETC complexes via increases in PPAR-α and PGC-1α expressions in the kidneys of Dahl-S rats. These results suggest that Ex may have beneficial effects on HS-induced mitochondrial dysfunction in the kidney.
Subject(s)
Hypertension , Kidney , Rats , Animals , Male , Rats, Inbred Dahl , Kidney/metabolism , Sodium Chloride , Sodium Chloride, Dietary , PPAR alpha/metabolism , Fatty Acids , Hypertension/metabolism , Blood PressureABSTRACT
BACKGROUND: With improved prognosis after lung transplantation (LTx), improving health-related quality of life (HRQL) in patients who have undergone LTx is a key goal. Although HRQL is improved significantly after transplantation, it is poorer than that in ordinary healthy people. However, the factors associated with poor HRQL remain unclear. This cross-sectional study aimed to identify the factors associated with poor HRQL in patients who have undergone LTx. METHODS: Between December 2018 and May 2022, 80 patients who had undergone LTx completed St. George's Respiratory Questionnaire (SGRQ) as a disease-specific quality of life measure, the Short Form-12 (SF-12) as a generic quality of life measure, and modified Medical Research Council (mMRC) scale of dyspnea. The groups were assigned according to the median SGRQ-total score and the Japanese population standard for SF-12, and those with good HRQL were compared with those with poor HRQL. Independent factors were evaluated using multivariate analysis. RESULTS: With regard to the SGRQ, there were significant differences in the forced expiratory volume in 1 s (FEV1) (P = 0.041), use of bronchodilators (P = 0.026), 6-min walk distance (6MWD) (P < 0.001), and Mmrc (P < 0.001) between better and poorer HRQL. For the SF-12 physical component summary score (PCS), age (P = 0.017), sex (P = 0.011), FEV1 (P < 0.001), forced vital capacity (FVC) (P < 0.001), diagnosis (P = 0.011), handgrip force (P = 0.003), 6MWD (P < 0.001), and Mmrc (P < 0.001) varied. Multivariate analyses revealed that Mmrc was the only independent factor in the SGRQ (P < 0.001, odds ratio [OR] = 6.65, 95% confidence interval [CI]: 2.49-17.74) and SF-12 PCS (P = 0.001, OR = 0.185, 95% CI: 0.07-0.52). There were significant correlations between the SGRQ-Total score and SF-12 PCS (correlation coefficient = -0.612, P < 0.001). CONCLUSIONS: Dyspnea may be an independent factor of poor disease-specific and generic HRQL in LTx patients. The management of dyspnea may improve the HRQL in patients who have undergone LTx.
Subject(s)
Lung Transplantation , Pulmonary Disease, Chronic Obstructive , Humans , Quality of Life , Cross-Sectional Studies , Hand Strength , Dyspnea , Surveys and QuestionnairesABSTRACT
BACKGROUND AND PURPOSE: Yoga has been studied as a rehabilitation option, but barriers to attendance remain. Videoconferencing, where participants can receive online, real-time instruction and supervision, may reduce the barriers. However, whether exercise intensity is equivalent to that of in-person yoga, and the relationship between proficiency and intensity remain unclear. The present study aimed to investigate whether the intensity of exercise is different between real-time remotely-delivered yoga via videoconferencing (RDY) and in-person yoga (IPY) and its relationship to proficiency. MATERIALS AND METHODS: Healthy yoga beginners (n = 11) and yoga practitioners (n = 11) performed yoga (Sun Salutation) consisting of 12 physical postures in real-time remotely delivered via videoconferencing and in-person (RDY, IPY, respectively), each for 10 min on different days, in random order, using an expiratory gas analyzer. Oxygen consumption was collected, metabolic equivalents (METs) were calculated based on the data, exercise intensity was compared between RDY and IPY, and differences of METs between beginners and practitioners in both interventions were also assessed. RESULTS: Twenty-two participants (mean age ± standard deviation, 47.2 ± 10.8 years) completed the study. There were no significant differences in METs between RDY and IPY (5.0 ± 0.5, 5.0 ± 0.7, respectively, P = 0.92), and no difference by proficiency level in both RDY (beginners: 5.0 ± 0.4, practitioners: 5.0 ± 0.6, P = 0.77) and IPY (beginners: 5.0 ± 0.7, practitioners: 5.0 ± 0.7, P = 0.91). No serious adverse events occurred in both interventions. CONCLUSION: The exercise intensity of RDY is equivalent to IPY regardless of proficiency with no adverse events in RDY occurring in this study.
Subject(s)
Yoga , Humans , Exercise , Health Status , Oxygen Consumption , VideoconferencingABSTRACT
INTRODUCTION: High-fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) has antihypertensive and renal protective effects in rats fed HFr; however, there has been little discussion about the DS rats, which exhibit metabolic disturbances. This study thus examined the effects of Ex on DS rats fed HFr. METHODS: Male DS rats were divided into three groups. The control group was fed a control diet, and both the HFr group and the HFr-Ex group were fed an HFr (60% fructose). The HFr-Ex group also underwent treadmill running (20 m·min -1 , 60 min·d -1 , 5 d·wk -1 ). After 12 wk, renal function, histology, and renin-angiotensin system were examined. RESULTS: HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor, and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type 2 receptor, and Mas receptor, and Ex restored the ACE2 and Mas receptor expressions to the control levels and further decreased the angiotensin II type 2 receptor expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels. CONCLUSIONS: Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal renin-angiotensin system may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.
Subject(s)
Hypertension , Renin , Male , Rats , Animals , Renin/metabolism , Renin/pharmacology , Receptor, Angiotensin, Type 2/metabolism , Rats, Inbred Dahl , Antihypertensive Agents , Fructose/adverse effects , Fructose/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/pharmacology , Kidney/physiology , Hypertension/chemically induced , Hypertension/prevention & control , Blood PressureABSTRACT
Partial foot amputation (PFA) is generally planned to minimize the amputation level; nonetheless, the effect of PFA levels on gait independence in amputees remains unclear. This study aimed to investigate the impact of PFA levels of the forefoot on gait independence in patients with chronic lower extremity (LE) wounds. This multicenter retrospective cohort study included 232 hospitalized Japanese patients treated and rehabilitated for chronic LE wounds. A multivariate analysis based on PFA levels was conducted for gait independence at discharge, with age and comorbidities as independent variables. Patients with Lisfranc amputation had significantly less independent gait than patients with more distal amputation and those without amputation (<22% vs >40%; P = .027; Fisher's exact test). Logistic regression analysis revealed that Lisfranc amputation (odds ratio [OR]: 0.257, P = .047), age (OR: 0.559, P = .043), and chronic limb-threatening ischemia (OR: 0.450, P = .010) were independent factors associated with gait independence. Additionally, the regression model confirmed discrimination performance using the C index (0.691, P < .001) with receiver operating characteristic analysis. In patients with chronic LE wounds undergoing PFA, Lisfranc amputation was negatively associated with gait independence.
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BACKGROUND: The impact of exercise tolerance on renal function change after acute myocardial infarction (AMI) is not clear. OBJECTIVES: The present study aimed to elucidate the effect of peak exercise oxygen uptake (VO2) levels on longitudinal changes in renal function up to 1 year after onset of AMI. METHODS: This retrospective longitudinal study enrolled 198 AMI patients. Symptom-limited cardiopulmonary exercise testing was performed at completion of early Phase II cardiac rehabilitation, and peak VO2 levels were defined as the primary exposure factor. The estimated glomerular filtration rates (eGFRs) at baseline, 3 months, 6 months and 1 year were collected. Generalized estimating equation (GEE) models were used to test the longitudinal effect of peak VO2 levels on within-patient changes in eGFR. RESULTS: Patients were stratified into tertile groups (Low group, 12.3 ± 1.3 mL/kg/min; Mid group, 15.3 ± 0.7 mL/kg/min; and High group, 19.1 ± 2.3 mL/kg/min) according to peak VO2 levels. The slopes of eGFR over 1 year in the Low (p = 0.024) and Mid groups (p = 0.037) were lower compared to the High group. The Low group had a significantly higher odds ratio of experiencing rapid renal function decline than the High group (odds ratio, 2.87; p = 0.012). CONCLUSIONS: There was a significant effect of lower peak VO2 on rapid decline in renal function after AMI. Our findings suggest that the coexistence of exercise intolerance may be a novel risk factor for rapid decline in renal function after AMI.
Subject(s)
Myocardial Infarction , Humans , Retrospective Studies , Longitudinal Studies , Exercise Tolerance , Exercise Test , Kidney/physiology , Oxygen , Oxygen ConsumptionABSTRACT
OBJECTIVES: Delirium is an important prognostic factor in postoperative patients undergoing cardiovascular surgery and intervention, including transcatheter aortic valve implantation (TAVI). However, delirium after transcatheter aortic valve implantation (DAT) is difficult to predict and its pathophysiology is still unclear. We aimed to investigate whether preoperative cerebral blood flow (CBF) is associated with DAT and, if so, whether CBF measurement is useful for predicting DAT. METHODS: We evaluated CBF in 50 consecutive patients before TAVI (84.7±4.5 yrs., 36 females) using 99mTc ethyl cysteinate dimer single-photon emission computed tomography. Preoperative CBF of the DAT group (N = 12) was compared with that of the non-DAT group (N = 38) using whole brain voxel-wise analysis with SPM12 and region of interest-based analysis with the easy-Z score imaging system. Multivariable logistic regression analysis with the presence of DAT was used to create its prediction model. RESULTS: The whole brain analysis showed that preoperative CBF in the insula was lower in the DAT than in the non-DAT group (P<0.05, family-wise error correction). Decrease extent ratio in the insula of the DAT group (17.6±11.5%) was also greater relative to that of the non-DAT group (7.0±11.3%) in the region of interest-based analysis (P = 0.007). A model that included preoperative CBF in the insula and conventional indicators (frailty index, short physical performance battery and mini-mental state examination) showed the best predictive power for DAT (AUC 0.882). CONCLUSIONS: These results suggest that preoperative CBF in the insula is associated with DAT and may be useful for its prediction.
Subject(s)
Aortic Valve Stenosis , Delirium , Transcatheter Aortic Valve Replacement , Female , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Tomography, Emission-Computed, Single-Photon , Brain/blood supply , Delirium/diagnostic imaging , Delirium/etiology , Perfusion , Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Treatment Outcome , Risk FactorsABSTRACT
Background: Although patients receiving hemodialysis are more likely to develop metabolic disorders and muscle weakness at an earlier stage than healthy individuals, many older dialysis patients have difficulty establishing exercise habits to prevent these problems. Therefore, we evaluated the use of belt electrode-skeletal muscle electrical stimulation (B-SES), which can stimulate a wider area than conventional electrical muscle stimulation (EMS), to examine its application and safety in older hemodialysis patients as a means to improve lower extremity function without voluntary effort. Methods: This study was a randomized controlled trial (RCT) involving 20 older dialysis patients (>65 years old) with reduced physical activity. The control group received 12 weeks of routine care only and the intervention group received 12 weeks of B-SES during hemodialysis in addition to routine care. The primary endpoint was the 6 min walk test (6MWT) distance, while the Short Physical Performance Battery (SPPB), body composition, Functional Independence Measure (FIM), biochemistry test, and blood pressure/pulse measurements were used as secondary endpoints. Results: As a result of the 12-week B-SES intervention, no increase in creatine kinase or C-reactive protein levels was observed after the intervention in either group, and no adverse events attributed to the B-SES intervention were observed in the intervention group. Furthermore, the intervention group showed a significant improvement in the 6MWT and SPPB scores after the intervention. Conclusions: The results of this study suggest that a 12-week B-SES intervention during hemodialysis sessions safely improves 6MWT distance and SPPB scores in older patients with a reduced level of physical activity.
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In patients with chronic kidney disease, exercise training with moderate intensity protects renal function and improves mortality. However, the mechanisms of the renal protective effects of exercise training in chronic kidney disease have not been clarified. This study investigated the effects of exercise training on renal NADPH oxidative and xanthine oxidase, which are major sources of reactive oxygen species, in rats with chronic renal failure. Six-week-old, male Sprague-Dawley rats were divided into the sham operation, 5/6 nephrectomy (Nx)+ sedentary, and Nx+ exercise training groups. The Nx+ exercise training group underwent treadmill running. After 12 weeks, systolic blood pressure, renal function, malondialdehyde, renal NADPH oxidase, and xanthine oxidase were examined. Nx induced hypertension, proteinuria, and renal dysfunction, and exercise training attenuated these disorders. Although the plasma levels of malondialdehyde were not different among the group, urinary levels were increased by Nx and decreased by exercise training. Renal activity and expression of NADPH oxidase and xanthine oxidase were increased by Nx and decreased by exercise training. These results indicate that exercise training attenuates hypertension and renal dysfunction and ameliorates NADPH oxidase and xanthine oxidase in rats with chronic renal failure, suggesting that the reduction of reactive oxygen species generation may be involved in the renal protective effects of exercise training.
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Left ventricular assist devices (LVAD) improve quality of life (QOL) in many patients with end-stage severe heart failure, but not in some patients. In addition, the burden on caregivers is expected to increase after LVAD patients are discharged. Our study aimed to investigate the impact of LVAD on the QOL of patients and caregivers. Thirty-two LVAD patients were assessed for changes in QOL, mental status, and activity level using the Euro QOL (EQ-5D-5L), Short Form 12 (SF-12), Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale (HADS), and Frenchay Activities Index. Twenty-four caregivers were assessed for changes in QOL, mental status, and burden of care using the EQ-5D-5L, SF-12, HADS, and Burden Index of Caregiver (BIC-11). The LVAD patients and caregivers responded contemporaneously regarding two points: pre-and post-LVAD. Patients' physical and mental QOL was significantly improved, but not social QOL and activity level. Caregivers' QOL and burden of care did not change, and anxiety was reduced (p = 0.028). The patients were divided into two groups based on whether EQ-5D-5L was improved: twelve patients in the unimproved group (UG) and twenty patients in the improved group (IG). In the UG, 50% had LVAD-related strokes (p = 0.001, IG: 0%), and their social QOL decreased (p = 0.023). The activity levels improved in the IG. Multi-dimensional analyses on the QOL in LVAD patients yielded mixed results. Anticipated benefits derived from LVAD therapy may be limited by LVAD-related complications such as stroke that negatively impacts on the QOL.
Subject(s)
Heart Failure , Heart-Assist Devices , Caregivers , Heart Failure/surgery , Humans , Japan , Quality of LifeABSTRACT
PURPOSE: Exercise training (Ex) has antihypertensive and renal protective effects; however, the precise mechanisms remain unclear. The renal renin-angiotensin system (RAS) plays a vital role in renal function and pathology. Therefore, we investigated the effects of Ex on the renal RAS components in Dahl salt-sensitive (Dahl-S) rats. METHODS: Male Dahl-S rats were divided into four groups: normal salt diet + sedentary, normal salt diet + Ex, high-salt diet (HS, 8% NaCl) + sedentary, and HS + Ex. Treadmill running was performed for 8 wk in the Ex groups. RESULTS: Ex attenuated the HS-induced renal dysfunction and glomerular injury without causing blood pressure alterations. HS increased urinary excretion of both total and intact angiotensinogen. Ex decreased the HS-induced increased urinary excretion of total angiotensinogen. However, it did not change the HS-induced urinary excretion of intact angiotensinogen, indicating reduced intact angiotensinogen cleaving. Ex restored the HS-induced increased angiotensinogen and angiotensin II type 1 receptor expressions in the outer medulla and the HS-induced increased angiotensin-converting enzyme expression in the cortex. Ex restored the HS-induced decreased renin expression in the cortex and outer medulla, and the HS-induced decreased angiotensin-converting enzyme 2, angiotensin II type 2 receptor, and Mas receptor expressions in the outer medulla. CONCLUSIONS: Ex attenuates HS-induced renal dysfunction, glomerular injury, and renal RAS dysregulation in Dahl-S rats.
Subject(s)
Hypertension , Physical Conditioning, Animal , Renin-Angiotensin System , Angiotensinogen/metabolism , Angiotensinogen/urine , Animals , Blood Pressure , Kidney , Male , Rats , Rats, Inbred Dahl , Renin-Angiotensin System/physiologyABSTRACT
OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.
Subject(s)
Exercise , Quality of Life , Canada , Humans , Kidney , PolicyABSTRACT
OBJECTIVE: Several clinical studies have reported that xanthine oxidoreductase inhibitors have antihypertensive and renal protective effects but their mechanisms have not been fully determined. This study aims to clarify these mechanisms by examining the effects of febuxostat, which is a novel selective xanthine oxidoreductase inhibitor, in Dahl salt-sensitive rats. METHODS: Eight-week-old male Dahl salt-sensitive rats were fed a normal salt (0.6% NaCl) or high salt (8% NaCl) diet for 8âweeks. A portion of the rats that were fed high salt diet were treated with febuxostat (3âmg/kg per day) simultaneously. Additionally, acute effects of febuxostat (3âmg/kg per day) were examined after high salt diet feeding for 4 or 8âweeks. RESULTS: Treatment with febuxostat for 8âweeks attenuated high salt diet-induced hypertension, renal dysfunction, glomerular injury, and renal interstitial fibrosis. Febuxostat treatment reduced urinary excretion of H2O2 and malondialdehyde and renal thiobarbituric acid reactive substances content. High salt diet increased xanthine oxidoreductase activity and expression in the proximal tubules and medullary interstitium. Febuxostat completely inhibited xanthine oxidoreductase activity and attenuated the high salt diet-increased xanthine oxidoreductase expression. Febuxostat transiently increased urine volume and Na+ excretion without change in blood pressure or urinary creatinine excretion after high salt diet feeding for 4 or 8âweeks. CONCLUSION: Febuxostat ameliorates high salt diet-induced hypertension and renal damage with a reduction of renal oxidative stress in Dahl salt-sensitive rats. The antihypertensive effect of febuxostat may be mediated in part by diuretic and natriuretic action.