Ventral hippocampal cholecystokinin interneurons gate contextual reward memory.

Associating contexts with rewards depends on hippocampal circuits, with local inhibitory interneurons positioned to play an important role in shaping activity. Here, we demonstrate that the encoding of context-reward memory requires a ventral hippocampus (vHPC) to nucleus accumbens (NAc) circuit that is gated by cholecystokinin (CCK) interneurons. In a sucrose conditioned place preference (CPP) task, optogenetically inhibiting vHPC-NAc terminals impaired the acquisition of place preference. Transsynaptic rabies tracing revealed vHPC-NAc neurons were monosynaptically innervated by CCK interneurons. Using intersectional genetic targeting of CCK interneurons, ex vivo optogenetic activation of CCK interneurons increased GABAergic transmission onto vHPC-NAc neurons, while in vivo optogenetic inhibition of CCK interneurons increased cFos in these projection neurons. Notably, CCK interneuron inhibition during sucrose CPP learning increased time spent in the sucrose-associated location, suggesting enhanced place-reward memory. Our findings reveal a previously unknown hippocampal microcircuit crucial for modulating the strength of contextual reward learning.

Age dependent path integration deficit in 5xFAD mice.

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia in elderly individuals, characterized by memory deficits, cognitive decline, and neuropathology. The identification of preclinical markers for AD remains elusive. We employed an ultrasound-evoked spatial memory assay to investigate path integration (PI) in wild type C57BL/6 J and 5xFAD mice. We observed significant recruitment of the mammillary bodies (MB) and subiculum (Sub) - core regions of the Papez circuit during PI, as indicated by increased expression of the immediate early gene c-Fos in C57BL/6 J mice. In 5xFAD mice, amyloid-beta (Aß) vulnerability in the MB and Sub was evident at 3-months of age, preceding widespread pathology at 5-months of age. In parallel, we detected significant behavioral deficits in PI in the 5XFAD mice at 5- but not 3-months of age. Sex based analysis revealed a more profound deficit in males compared to females at 5-months of age. Our data suggest PI may be as an early indicator of AD, potentially associated with dysfunction within the Papez circuit.

Factors associated with gait speed: results from the RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients (RECOVERY) study.

Background: Gait speed is an important measure of functional ability. This study aimed to investigate the factors associated with gait speed in patients with chronic kidney disease. The study focused on sarcopenic components, plasma uremic or inflammatory marker levels, and quality of life effects. Methods: The RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients is a 48-week, randomized controlled, parallel-group, open-label, multicenter trial to determine the role of Renamezin (Daewon Pharmaceutical Co., Ltd.) in patients with chronic kidney disease. The participants were classified into four groups according to gait speed: ≤0.8, 0.8-1.0, ≤1.0-1.3, and ≥1.3 m/sec. Linear regression analysis was performed to identify the factors associated with gait speed. Results: The group with a gait speed of ≤0.8 m/sec was the oldest and had the highest proportion of participants with low education level and medical aid. Participants with a gait speed of ≤0.8 m/sec showed the lowest physical and mental component scale scores. The interleukin-6 (IL-6) level tended to be the higher trend in the lowest gait speed group. In the multivariate linear regression analysis adjusted for age, sex, diabetes mellitus, and estimated glomerular filtration rate, insurance status, handgrip strength, IL-6 level, hemoglobin level, mental component scale score, and physical component scale score were significantly associated with gait speed. Conclusion: In conclusion, gait speed is associated with handgrip strength, IL-6 level, and various components of quality of life in predialysis chronic kidney disease patients.

Impact of volume status on sarcopenia in non-dialysis chronic kidney disease patients.

There were few data regarding the association of volume status with sarcopenia using muscle mass, strength, and physical performance in non-dialysis chronic kidney disease (ND-CKD) patients. We aimed to evaluate the association between volume status and sarcopenia in ND-CKD patients. Our retrospective study analyzed data from a previous study which included ND-CKD patients who had stable renal function. Our study used its baseline data alone. The edema index and muscle mass were measured using a multi-frequency bioimpedance analysis machine. The edema index was calculated using extracellular water/total body water ratio. The skeletal muscle index (SMI, kg/m2) was calculated using appendicular muscle mass per height squared. Handgrip strength (HGS, kg) was measured during the standing position in all patients. Dynamic gait speed (GS, m/s) was evaluated using 6-m walking speed. Patients with both low muscle mass (SMI < 7.0 kg/m2 for men and < 5.7 kg/m2 for women using bioimpedance analysis) and low HGS (< 28 kg for men and < 18 kg for women) or low GS (< 1.0 m/s) were classified as having sarcopenia. The patients (n = 147) were divided into tertiles based on the edema index level. The mean edema index in the low, middle, and high tertiles was 0.377 ± 0.006, 0.390 ± 0.003, and 0.402 ± 0.006, respectively. The edema index was significantly correlated with SMI, HGS, and GS (r = - 0.343 for SMI, - 0.492 for HGS, and - 0.331 for GS; P < 0.001 for three indicators). The SMI, HGS, and GS values were 8.1 ± 1.0 kg/m2, 33.0 ± 9.4 kg, and 1.2 ± 0.2 m/s in the low tertile,7.8 ± 1.2 kg/m2, 30.0 ± 7.5 kg, and 1.0 ± 0.3 m/s in the middle tertile, and 7.2 ± 1.4 kg/m2, 23.7 ± 7.4 kg, and 1.0 ± 0.3 m/s in the high tertile, respectively. Univariate analyses revealed that SMI was lower in patients in the high tertile than in those in the low tertile. HGS was lowest in high tertile, and GS was greatest in the low tertile. The high tertile for predicting sarcopenia had an odds ratio of 6.03 (95% CI, 1.78-20.37; P = 0.004) compared to low or middle tertiles. The results of multivariate analyses were similar to those of the univariate analyses. The subgroup analyses showed that statistical significance was greater in < 65 years and men than ≥ 65 years and women. The present study showed that the edema index is inversely associated with sarcopenia, muscle mass index, strength, and physical performance in ND-CKD patients. However, considering the limitations of our study such as its small sample size, this association was not strong. Further studies that include volume-independent measurements, data on physical activity and diet, and a larger number of patients are warranted to overcome these limitations.

Indoxyl Sulfate Might Play a Role in Sarcopenia, While Myostatin Is an Indicator of Muscle Mass in Patients with Chronic Kidney Disease: Analysis from the RECOVERY Study.

Serum myostatin and indoxyl sulfate (IS) levels increase with kidney function decline and may function as uremic toxins in chronic kidney disease (CKD)-related sarcopenia. Herein, we analyzed the association between serum myostatin and IS levels and sarcopenia in patients with CKD, by performing a post hoc analysis of baseline data extracted from the RECOVERY study (clinicaltrials.gov: NCT03788252) of 150 patients with CKD. We stratified patients into two groups according to the median value of myostatin (cutoff 4.5 ng/mL) and IS levels (cutoff 0.365 mg/dL). The proportion of patients with sarcopenia was higher in those with high IS levels but lower in those with high myostatin levels. The skeletal muscle mass index (SMI) and handgrip strength (HGS) were significantly lower in patients with high IS levels but significantly higher in patients with high myostatin levels. IS levels showed a negative correlation with glomerular filtration rate (GFR), SMI, and HGS. However, myostatin levels were positively correlated with SMI and HGS, but not with GFR. Sarcopenia was independently associated with age and IS level after adjustment. Increased levels of serum total IS might play a role in sarcopenia, while increased levels of serum myostatin are associated with muscle mass in patients with CKD.

Hippocampus-Anterior Hypothalamic Circuit Modulates Stress-Induced Endocrine and Behavioral Response.

Hippocampal input to the hypothalamus is known to be critically involved in mediating the negative feedback inhibition of stress response. However, the underlying neural circuitry has not been fully elucidated. Using a combination of rabies tracing, pathway-specific optogenetic inhibition, and cell-type specific synaptic silencing, the present study examined the role of hippocampal input to the hypothalamus in modulating neuroendocrine and behavioral responses to stress in mice. Transsynaptic rabies tracing revealed that the ventral hippocampus (vHPC) is monosynaptically connected to inhibitory cells in the anterior hypothalamic nucleus (AHN-GABA cells). Optogenetic inhibition of the vHPC→AHN pathway during a restraint stress resulted in a prolonged and exaggerated release of corticosterone, accompanied by an increase in stress-induced anxiety behaviors. Consistently, tetanus toxin-mediated synaptic inhibition in AHN-GABA cells produced a remarkably similar effect on the corticosterone release profile, corroborating the role of HPC→AHN pathway in mediating the hippocampal control of stress responses. Lastly, we found that chronic inhibition of AHN-GABA cells leads to cognitive impairments in both object and social recognition memory. Together, our data present a novel hypothalamic circuit for the modulation of adaptive stress responses, the dysfunction of which has been implicated in various affective disorders.

Phase angle as a marker for muscle health and quality of life in patients with chronic kidney disease.

BACKGROUND & AIMS: Sarcopenia is associated with adverse health outcomes in individuals with chronic kidney disease (CKD); hence, a convenient and reliable method for monitoring muscle health is required. This study investigated the utility of the phase angle (PhA) to estimate muscle health and health-related quality of life (HRQoL) in patients with CKD. METHODS: Data were obtained from a multicenter randomized trial that examined the effect of AST-120 on sarcopenia and HRQoL. The PhA and skeletal muscle mass index (SMI) were derived from bioelectrical impedance analyses at baseline, 24-week, and 48-week. In addition, handgrip strength (HGS), 6 m gait speed (GS), and HRQoL were obtained simultaneously. RESULTS: In total, 149 participants were included. PhA was linearly related to SMI, HGS, and GS (r = 0.616, 0.619, and 0.290, respectively; all P < 0.001). Moreover, PhA was associated with the criteria for low muscle mass and low muscle strength (both P < 0.001), and it predicted the presence of sarcopenia (P = 0.001). Substantial agreement was observed in the diagnosis of sarcopenia (κ = 0.510; P < 0.001). In addition, PhA was related to various aspects of HRQoL, including physical functioning, general health, mental health, physical component scale, mental component scale, work status, quality of social interaction, sexual function, and social support. In the longitudinal analysis, SMI increased in the increasing PhA group (a PhA slope ≥ 0.2° per year), and HGS was reduced in the decreasing PhA group (a PhA slope of < -0.2° per year) as compared to the constant PhA group (a PhA slope of -0.2 to 0.2° per year; both P = 0.054). The GS pattern did not differ among the three groups. In addition, the prevalence of sarcopenia was comparable at baseline (P = 0.220); however, its proportion rose in the decreasing PhA group and reduced in the increasing PhA group (P at 48-week = 0.058). With regards to aspects of HRQoL, role limitations due to physical health problems worsened in the decreasing PhA group. CONCLUSIONS: PhA appears to be a reliable marker for estimating muscle health and HRQoL in patients with CKD. In addition, monitoring PhA may help estimate the longitudinal patterns of muscle health and HRQoL.

Clinical Significance of Volume Status in Body Composition and Physical Performance Measurements in Hemodialysis Patients.

Introduction: This study aimed to evaluate the association between volume status and body composition or physical performance measurements in hemodialysis patients. Methods: A total of 84 patients were enrolled in this study. The participants were divided into tertiles based on the edema index (extracellular water/total body water): low, middle, and high tertiles. Serum albumin and serum high-sensitivity C-reactive protein levels were measured. The appendicular lean mass index (ALM/Ht2, kg/m2) was measured using dual-energy X-ray absorptiometry. The thigh muscle area index (TMA/Ht2, cm2/m2) was measured using CT. Extracellular and total body water and phase angles were obtained using bioimpedance analysis. The results of the subjective global assessment (SGA), hand-grip strength (HGS), gait speed (GS), short physical performance battery (SPPB), sit-to-stand for 30-second (STS30) test, timed up and go (TUG), sit-to-stand test performed five times (STS5), and 6-minute walk (6-MW) tests were also evaluated. Results: On the univariate analysis, the SGA score and phase angle in the high tertile group were the lowest among the three groups. On multivariate analysis, TMA/Ht2 and phase angle in the high tertile were the lowest among the three groups. Inverse correlations were observed between edema index and TMA/Ht2, SGA score, phase angle, HGS, GS, SPPB, STS30, or 6-MW. Positive correlations were observed between the edema index and the STS5 or TUG test. The sensitivity and specificity for predicting low GS were 34.5 and 89.7%, respectively. The values for predicting low SPPB were 68.0 and 79.7%, respectively. Conclusion: This study demonstrates that high volume status may be associated with decreased muscle mass and physical performance regardless of inflammatory or nutritional status.

Impedance-derived phase angle is associated with muscle mass, strength, quality of life, and clinical outcomes in maintenance hemodialysis patients.

INTRODUCTION: We aimed to evaluate the association between the phase angle and muscle mass, muscle strength, physical performance tests, quality-of-life scales, mood scales, or patient and hospitalization-free survival rates in hemodialysis (HD) patients. METHODS: We included 83 HD patients. The patients were divided into tertiles based on phase angle value. The phase angle was measured using a bioimpedance analysis machine. Thigh muscle area per height squared (TMA/Ht2), handgrip strength (HGS), nutritional indicators, physical performance, quality-of-life, depression or anxiety status, and the presence of hospitalization or death regardless of cause were evaluated. RESULTS: In our study, no significant differences were observed in the serum albumin level and body mass index according to tertiles of phase angle. The phase angle tertiles were associated with TMA/Ht2 and HGS. The phase angle was also associated with physical performance measurements and depression or anxiety status. Subgroup analyses according to sex, age, and diabetes mellitus showed similar trends to those of the total cohort. Furthermore, the hospitalization-free survival rate and patient survival rate were favorable in patients with high values for the phase angle. CONCLUSION: The present study demonstrated that the phase angle is associated with muscle mass, strength, physical performance, quality-of-life scale, and hospitalization-free survival in maintenance HD patients.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

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.

Effects of AST-120 on muscle health and quality of life in chronic kidney disease patients: results of RECOVERY study.

BACKGROUND: The prevalence of sarcopenia is increased with declining renal function. Elevated serum indoxyl sulfate levels are associated with poor skeletal muscle conditions. We aimed to determine the effects of AST-120, the oral adsorbent of indoxyl sulfate, on sarcopenia and sarcopenia-associated factors in chronic kidney disease patients. METHODS: This was a 48 week, randomized controlled, parallel group, open-label, multicentre trial (n = 150). The participants were randomly assigned in a 1:1 ratio to the control (CON) and AST-120 (Renamezin®, REN) groups. Outcome measurements were performed at baseline and every 24 weeks for 48 weeks. The primary outcome was gait speed difference ≥0.1 m/s between the two groups, and secondary outcomes included hand grip strength, muscle mass, and health-related quality of life. RESULTS: A difference of gait speed ≥0.1 m/s was not observed during the study period. The mean dynamic-start gait speed in the REN group increased from baseline to 48 weeks (1.04 ± 0.31 to 1.08 ± 0.32 m/s, P = 0.019). The static-start gait speed changed by -0.024 and 0.04 m/s (P = 0.049) in the CON and REN groups over 48 weeks, respectively. Hand grip strength decreased during the first 24 weeks and did not significantly change over the next 24 weeks in either group. The proportion of low muscle mass or sarcopenia at baseline was larger in the REN group than in the CON group, but the difference attenuated over the study period [low muscle mass and sarcopenia in the CON and REN groups at baseline, 4.0% vs. 18.9% (P = 0.004) and 2.7% vs. 13.5% (P = 0.017); at 24 weeks, 2.9% vs. 13.6% (P = 0.021) and 1.4% vs. 10.5% (P = 0.029); and at 48 weeks, 7.6% vs. 12.9% (P = 0.319) and 4.5% vs. 8.1% (P = 0.482), respectively]. Bodily pain, vitality, symptoms/problems, and cognitive function in the REN group improved, while the quality of social interactions and the kidney disease effects in the CON group aggravated from baseline to 48 weeks. Interaction between time and group was evident only in symptoms/problems, cognitive function, and kidney disease effects. CONCLUSIONS: The addition of AST-120 to standard treatment in chronic kidney disease patients did not make a significant difference in gait speed, although AST-120 modestly had beneficial effects on gait speed change and quality of life and showed the potential to improve sarcopenia. (clinicaltrials.gov: NCT03788252).

Comparison of appendicular lean mass indices for predicting physical performance in Korean hemodialysis patients: A cross-sectional study.

ABSTRACT: Few studies have examined the optimal adjustment indices for predicting low muscle strength or physical performance in hemodialysis (HD) patients. Thus, the present study aimed to identify optimal adjustment indices for predicting strength and/or physical performance in HD patients.Our study was performed at an HD center (n = 84). Appendicular lean mass (ALM; kg) was calculated using dual-energy X-ray absorptiometry. ALM were adjusted to body weight, height2 (Ht2), body surface area, or body mass index. Physical performance tests (sit-to-stand test performed 5 times test, sit-to-stand for 30 second test, 6-minute walk test, timed up and go test, gait speed, hand grip strength, average steps per day (AST), and short physical performance battery) were also evaluated. Participants with a below median value for each physical performance test were defined as the low group.The mean participant age was 55.6 ±â€Š12.8 years; 44 (52.4%) were men. The univariate analysis revealed a significant difference in ALM/Ht2 values between the low and normal physical performance group in all physical performance tests except short physical performance battery. The multivariate analysis revealed a significant difference in ALM/Ht2 between the low and normal physical performance groups in hand grip strength, 5 times sit-to-stand test, sit-to-stand for 30-second test, and AST. In women on HD, most indices were not associated with physical performance or strength.We demonstrated that, in men on HD, ALM/Ht2 may be the most valuable among various variables adjusted for ALM for predicting physical performance or strength.

Comparison of Body Composition, Strength, and Physical Performance Measurements Between Healthy Participants and Hemodialysis Patients.

PURPOSE: This study evaluated the difference in physical performance tests, strength, and total and regional mass using a comprehensive dataset between maintenance hemodialysis (HD) patients and a healthy population. PATIENTS AND METHODS: A total of 84 HD patients were enrolled. We selected 42 healthy participants (HPs) age- and sex-matched to the 84 HD patients as controls. Collected data were sex, age, body mass index (BMI), laboratory findings, total and regional measurements for lean mass or fat mass, thigh muscle area (TMA), handgrip strength, and physical performance measurements. RESULTS: There were no significant differences in BMI, total lean mass, or total fat mass including regional fat mass between the two groups. Lean leg mass and TMA were greater in HPs than in HD patients. All measurements of physical performance, including handgrip strength, were better in HPs than in HD patients. A multivariate analysis of lean leg mass, TMA, and physical performance measures had similar results to the same data studied with a univariate analysis. CONCLUSION: We demonstrated that HD patients had decreased physical performance and strength compared to HPs. The difference in leg muscle mass was most prominent among the total and regional body compositions between HPs and HD patients.

Comparisons of physical activity and understanding of the importance of exercise according to dialysis modality in maintenance dialysis patients.

Data regarding the status of physical activity or understanding of the importance of exercise, such as barriers of exercise or enablers of exercise, in dialysis patients were insufficient. This study aimed to evaluate the status of physical activity and the understanding of the importance of exercise in Korean dialysis patients. The study participants were recruited from 27 hospitals or dialysis centers (n = 1611). Physical activity was evaluated using the Korean version of the International Physical Activity Questionnaire-Short Form. High physical activity was defined as ≥ 600 metabolic equivalent of task (MET). Knowledge about the importance of exercise, enabler for regular exercise, benefits of exercise, and barrier to exercise was evaluated. Health-related quality of life (HRQoL) was assessed by the Kidney Disease Quality of Life version 1.3. The number of participants in the hemodialysis (HD) and peritoneal dialysis (PD) groups was 1247 and 364, respectively. The intensity of physical activity did not differ between the two modalities. The time of physical activity was longer in HD patients than in PD patients, which resulted in greater MET values and the number of high physical activity. There were 762 (61.1%) HD patients and 281 (77.2%) PD patients who heard of the importance of exercise (P < 0.001). In both HD and PD patients, dialysis staff played the most significant role as educators on the importance of exercise and enablers of exercise. The most important barriers to exercise were poor motivation and fatigue in both modalities. HD patients exhibited greater differences in HRQoL scales across two physical activity levels, compared to PD patients. Our study showed that the barrier to exercise and the enablers of exercise were poor motivation/fatigue and encouragement from dialysis staff, respectively.

Association Between the Normal-Density Psoas Muscle Index and Handgrip Strength or Gait Speed in Maintenance Hemodialysis Patients.

Introduction: This study aimed to evaluate the association between the psoas muscle (PM) index with or without fatty infiltration and various indices associated with muscle mass in hemodialysis (HD) patients. Methods: We included stable HD patients (n = 83). The collected data included subjective global assessment (SGA) score, ASM/Ht2 (appendicular skeletal muscle mass divided by the squared height in meters), gait speed (GS; m/s), and handgrip strength (HGS; kg). The abdominal computed tomography (CT) image was obtained using a CT scanner. The PM and normal-density PM (NPM) indices (mm2/m2) were calculated using the whole PM area or the area with an attenuation range of 35-100 HU divided by the squared height in meters. Results: Correlation coefficients for the SGA score, ASM/Ht2, HGS, and GS were greater for the NPM index than for the PM index. The linear regression analysis showed that, on multivariate analysis, the NPM index was significantly associated with the SGA score, ASM/Ht2, and GS. However, the PM index was significantly associated with the SGA score and ASM/Ht2 but not with HGS or GS. For calculating the low GS, the area under the receiver operating characteristic curve area was significantly greater for the NPM index than for the PM index (P = 0.012). Conclusion: The present study suggested that the NPM index excluding fatty infiltration may be an early and useful indicator for detecting muscle strength and physical performance among HD patients.

Myostatin/Appendicular Skeletal Muscle Mass (ASM) Ratio, Not Myostatin, Is Associated with Low Handgrip Strength in Community-Dwelling Older Women.

BACKGROUND/AIMS: Elevated levels of serum myostatin have been proposed as a biomarker for sarcopenia. Recent studies have shown that elevated level of serum myostatin was associated with physical fitness and performance. This study aimed to examine the significance of myostatin in the association between muscle mass and physical performance in the elderly. METHODS: This cross-sectional study is based on the Korean Frailty and Aging Cohort study involving 1053 people aged 70 years or over. Anthropometric, physical performance, and laboratory data were collected. RESULTS: The mean age of the participants was 75.8 years, and 50.7% of them were female. Serum myostatin levels in men (3.7 ± 1.2 vs. 3.2 ± 1.1 ng/mL, p < 0.001) were higher compared with that in women. Serum myostatin level was associated with appendicular skeletal muscle mass (ASM) index and eGFR by cystatin C. Serum myostatin/ASM ratio was associated with handgrip strength in women. CONCLUSION: Higher serum myostatin levels were related with higher muscle mass and better physical performances in the elderly. Serum myostatin/ASM ratio may be a predictor for physical performance rather than myostatin.

Association Between Alkaline Phosphatase and Muscle Mass, Strength, or Physical Performance in Patients on Maintenance Hemodialysis.

Introduction: Alkaline phosphatase (ALP) is an indicator for checking liver or bone disorders, but recent studies have shown the possibility of an additive indicator beyond the simple mineral-bone status in dialysis patients. The aim of the study was to evaluate the ALP level and various indicators for malnutrition, physical performance, or hospitalization in patients on hemodialysis (HD). Methods: This study was an observational study (n = 84). We included all patients undergoing HD with the following criteria: age ≥ 20 years, duration of dialysis ≥ 6 months, ability to ambulate without an assistive device, ability to communicate with the interviewer, and no hospitalization within the last 3 months before enrollment. Furthermore, none of the patients had liver disease. We recommended abstinence of alcohol for ≥ 1 month for the duration of the study. The patients were divided into tertiles based on the ALP level. Muscle mass [appendicular muscle mass index using dual-energy X-ray absorptiometry (ASM/Ht2), thigh muscle area index using computed tomography (TMA/Ht2)], strength [handgrip strength (HGS)], and physical performance [gait speed (GS), sit-to-stand for 30-s test (STS30), 6-min walk test (6-MWT), or Short Physical Performance Battery test (SPPB)] were evaluated. The number of hospitalizations was also evaluated. Results: The ALP level in the low, middle, and high tertiles was 50.5 ± 7.5, 69.8 ± 5.4, and 113.3 ± 47.3 IU/l, respectively. The high tertile group showed the poorest trends in ASM/Ht2, TMA/Ht2, HGS, GS, STS30, and 6-MWT compared to the other tertile groups. Logistic regression analysis showed that the high tertile group for low HGS, low GS, or low SPPB had a higher odds ratio compared to the other tertiles. Subgroup analyses according to age, sex and diabetes mellitus showed similar trends as in the total cohort. Hospitalization-free survival rates after 300 days in the high tertile and the other tertiles were 53.8 and 77.2%, respectively (P = 0.105). Conclusion: The present study demonstrated that ALP is associated with muscle mass, strength, and physical performance in patients on maintenance HD. In addition, the trend showed better hospitalization-free survival in the low or middle tertiles than in the high tertile. ALP can be considered as a simple and useful indicator to detect malnutrition, physical performance, or hospitalization in patients on HD.

The relationship between disability and clinical outcomes in maintenance dialysis patients.

BACKGRUOUND: Dialysis patients are prone to having disabilities. We aimed to evaluate the association between disability and various clinical outcomes in Korean dialysis patients. METHODS: This study consisted of 1,615 dialysis patients from 27 centers. We evaluated disability by using four questions on the activities of daily living (ADLs) concerning whether help was needed for feeding, dressing/undressing, getting in/out of bed, or taking a bath/shower. We divided the patients into three groups: no disability (Non-D, none of the four ADL domains required help; n=1,312), mild disability (Mild-D, one ADL domain required some/full help; n=163), or moderate to severe disability (MS-D, two or more ADL domains required some/full help; n=140). We evaluated falls, frailty, health-related quality of life (HRQoL), mortality, and hospitalization. RESULTS: The numbers of participants with a fall during the last 1 year were 199 (15.2%), 42 (25.8%), and 44 (31.4%) in the Non-D, Mild-D, and MS-D groups, respectively (p<0.001). The numbers of participants with frailty in the Non-D, Mild-D, and MS-D groups were 381 (29.0%), 84 (51.5%), and 93 (66.4%), respectively (p<0.001). In both univariate and multivariate analyses, the physical component scale and mental component scale scores decreased as the grade of disability increased (p<0.001 for both scores). Hospitalization-free survival rate at 500 days was 64.2%, 56.7%, and 51.1% in the Non-D, Mild-D, and MS-D, respectively (p=0.001 for trend). Patient survival rate at 500 days was 95.3%, 89.5%, and 92.3% in the Non-D, Mild-D, and MS-D, respectively (p=0.005 for trend). CONCLUSION: Disability was associated with falls, frailty, HRQoL scales, and survival trends in Korean dialysis patients.

Association between Vitamin D Level and Muscle Strength in Patients Undergoing Hemodialysis.

INTRODUCTION: Identification of the risk factors and treatment of the decrease in muscle mass or strength are important to improve the prognosis of patients undergoing hemodialysis (HD). Previous studies have investigated the association between vitamin D level and muscle mass or strength in patients undergoing HD. However, there are conflicting results regarding this association. OBJECTIVE: To evaluate the association between vitamin D level and muscle mass indices, strength, or physical performance in patients undergoing HD. METHODS: This study was performed in a tertiary medical center. We included patients undergoing HD aged ≥20 years. A total of 84 patients were enrolled. The patients were divided into tertiles based on the 25-hydroxy (25-OH) vitamin D level as follows: lowest tertile (Lowest T, n = 28), middle tertile (Middle T, n = 28), and highest tertile (Highest T, n = 28). We evaluated the association between the tertiles and clinical outcomes including nutritional status, muscle mass, muscle function, handgrip strength (HGS), physical performance, and health-related quality of life (HRQoL) scales. RESULTS: There were no significant differences in the muscle mass indices and nutritional markers according to tertiles of 25-OH vitamin D level. However, 25-OH vitamin D level as a continuous variable or the tertile of 25-OH vitamin D level as a categorical variable was positively associated with HGS. Logistic and linear regression analyses showed a consistent superiority of the Highest T in HGS compared with the Lowest or Middle T. Although the statistical significance was weak, the scores of various physical performance tests and the HRQoL scales were highest in the Highest T among the 3 tertiles. CONCLUSION: The present study demonstrated that serum vitamin D level is associated with HGS in patients undergoing HD regardless of muscle mass indices or nutritional status.