Prevalence and relevance of cachexia as diagnosed by two different definitions in patients undergoing hemodialysis: A retrospective and exploratory study.

OBJECTIVE: Cachexia is present in various chronic diseases and is associated with decreased quality of life and increased risk of morbidity and mortality. However, evidence regarding the association of cachexia with prognosis in patients undergoing hemodialysis is limited. We assessed cachexia using two definitions and compared prevalence, functional impairment, and prognostic impact in patients undergoing hemodialysis. METHODS: We enrolled outpatients undergoing hemodialysis at two centers retrospectively. We assessed cachexia using the conventional cachexia (Evans' criteria) and the Asian Working Group for Cachexia (AWGC) criteria. The study examined all-cause mortality and functional status (Clinical Frailty Scale and short physical performance battery). We used Cox proportional hazards model to examine the association with prognosis, and logistic regression analysis to examine the association with functional impairment. RESULTS: Among 367 patients (mean age, 67 years; 63 % male), cachexia prevalence, as defined by Evans' criteria and AWGC, was 21.3 % and 35.2 %, respectively. Cachexia as defined by Evans' criteria was associated with an increased risk of all-cause mortality (hazard ratio [HR], 95 % confidence interval [CI]: 1.81, 1.02-3.23). Also, cachexia as defined by AWGC criteria showed suggestive association with increasing mortality (HR, 95 % CI: 1.56, 0.90-2.70). Similar results were seen between cachexia and functional impairment. CONCLUSIONS: Among patients on hemodialysis, cachexia was highly prevalent and was associated with poor prognosis and functional impairment. Detecting cachexia in earlier stages may be useful for risk stratification in this population.

Prevalence of osteosarcopenia and its association with mortality and fractures among patients undergoing hemodialysis.

INTRODUCTION: Osteosarcopenia is an age-related syndrome characterized by the coexistence of osteoporosis and sarcopenia. Little is known about the clinical implications of osteosarcopenia among patients undergoing hemodialysis. This study investigated the prevalence of osteosarcopenia and its association with all-cause mortality and fractures in this population. MATERIALS AND METHODS: This retrospective cohort study included outpatients undergoing hemodialysis in Japan. Sarcopenia was defined according to the recommendations of the Asian Working Group for Sarcopenia 2019. Osteoporosis was defined as a T-score of the calcaneus bone < - 2.5. We divided patients into three groups: robust (no osteoporosis or sarcopenia), osteoporosis or sarcopenia alone (osteoporosis without sarcopenia or sarcopenia without osteoporosis), and osteosarcopenia (osteoporosis and sarcopenia). Cox proportional-hazard and negative binomial regression models were used to estimate the associations between osteosarcopenia and all-cause mortality and fractures. RESULTS: Among the 328 patients (mean age, 65.5 ± 11.3 years; men, 59.1%), the prevalence of osteosarcopenia was 22.9%. During the follow-up period (1972 person-years), 131 deaths and 113 fractures occurred. Patients with osteoporosis or sarcopenia alone (hazard ratio 1.36; 95% confidence interval 0.85-2.18) and osteosarcopenia (hazard ratio 2.13; 95% confidence interval, 1.23-3.68) showed a higher risk of all-cause mortality than the robust group. Similar results were observed for the risk of fractures in patients with osteosarcopenia. CONCLUSIONS: Patients undergoing hemodialysis showed a high prevalence of osteosarcopenia, and osteosarcopenia was associated with a poor prognosis in this patient population. Assessing osteosarcopenia may be useful for accurate prognostic stratification of patients undergoing hemodialysis.

Association between Physical Frailty and Sleep Disturbances among Patients on Hemodialysis: A Cross-Sectional Study.

INTRODUCTION: Among patients on hemodialysis (HD), physical frailty and sleep disturbances are not only common but also associated with adverse outcomes. The aim of this study was to evaluate the association between physical frailty and sleep disturbances in patients on HD. METHODS: This cross-sectional study was conducted from June 2017 to March 2021, with outpatients receiving HD 3 times a week at two dialysis facilities in Japan. Sleep disturbances were identified with the Athens Insomnia Scale (AIS). Physical frailty was defined using the Fried Frailty Phenotype. Patients were classified as "non-frailty (number of frailty components: 0-2)" or "frailty (3-5)." We examined the association of sleep disturbances with physical frailty and its components by performing a logistic regression analysis. RESULTS: We analyzed 360 patients (mean age 65.6 years; 62% men). Eighty-one patients (23%) were classified into the group with frailty, and the mean AIS score was 5.2 ± 4.2 points. After adjusting for clinical characteristics, increasing the AIS score per 1 point was associated with higher odds of physical frailty (odds ratio, 1.12; 95% confidence interval, 1.05-1.20; p < 0.01). As for the frailty components, exhaustion, low physical activity, and weak grip strength showed an association with sleep disturbances (all p < 0.05). CONCLUSIONS: Sleep disturbances were independently associated with physical frailty in patients on HD. Future studies are warranted to investigate the causality between physical frailty and sleep disturbances in this population.

The Association of Short Physical Performance Battery With Mortality and Hospitalization in Patients Receiving Hemodialysis.

OBJECTIVE: The Short Physical Performance Battery (SPPB) is recommended for evaluating physical performance in patients on hemodialysis (HD). However, the association between SPPB score and long-term health outcomes in these patients remains unclear. We examined the association of SPPB score with all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization in patients on HD. DESIGN AND METHODS: This retrospective cohort study included 326 patients (median age, 68 years; 62% men) who received outpatient HD therapy. These patients were divided into 2 SPPB groups: low (SPPB ≤9) and high (SPPB >9). We investigated the association of SPPB score and their change over time with health outcomes using Cox regression analysis. RESULTS: Low SPPB score was associated with a higher risk for all-cause mortality (hazard ratio [HR]: 3.19, 95% confidence interval [95% CI]: 1.89-5.38), all-cause hospitalization (HR: 2.01, 95% CI: 1.44-2.82), and cardiovascular hospitalization (HR: 2.20, 95% CI: 1.45-3.35). Additionally, change in SPPB score over 1 year was associated with health outcomes. CONCLUSIONS: Lower SPPB score was significantly associated with a higher risk for all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. The SPPB may be a valuable indicator for risk stratification in patients on HD. Additionally, preventive treatments may be an effective management strategy in limiting the high mortality and hospitalization rates in patients with decreased SPPB score.

Prevalence, overlap, and prognostic impact of multiple frailty domains in older patients on hemodialysis.

BACKGROUND: Frailty is a state of increased vulnerability owing to adverse health outcomes and is recognized as a multidimensional construct. There is limited evidence on the association between multiple domains of frailty and the risk of adverse events in patients undergoing hemodialysis. We aimed to report on the prevalence, degree of overlap, and prognostic impact of multiple frailty domains in older patients undergoing hemodialysis. METHODS: We retrospectively enrolled outpatients (aged ≥60 years) undergoing hemodialysis at two dialysis centers in Japan. The physical domain of frailty was defined as slow gait speed and low handgrip strength. The psychological and social domains of frailty were defined using a questionnaire to assess depressive symptoms and define social frailty status. The outcomes were all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. Cox proportional hazard and negative binomial models were used to examine these associations. RESULTS: Among the 344 older patients (mean age, 72 years; male, 61%), 15.4% had an overlap in all three domains. Patients with a higher number of frailty domains had a higher risk of all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization (P for trend = 0.001, 0.001, and 0.08, respectively). CONCLUSIONS: These results suggest that multiple-domain assessment of frailty is an important strategy to prevent adverse events in patients requiring hemodialysis.

Reserved gait capacity and mortality among patients undergoing hemodialysis.

BACKGROUND: Patients undergoing hemodialysis (HD) have difficulty increasing their gait speed in daily life. The extent of the increase from the usual gait speed (UGS) to the maximum gait speed (MGS) is considered the reserved gait capacity (RGC). Little is known regarding the implications of RGC. This study aimed to investigate the association between RGC and all-cause mortality in patients undergoing HD. METHODS: In this retrospective study, we assessed the usual and maximum 10-m walking speed of outpatients who underwent HD between October 2002 and August 2021. RGC was defined as the ratio of MGS to UGS. Patients were divided into three groups according to the tertiles of RGC (low, moderate and high). A Cox proportional hazards regression model was used to examine the association between RGC and all-cause mortality. RESULTS: Of the 496 (median age 66.0 years; men 59%) participants, 186 patients died during the follow-up (incident ratio of 62.0 per 1000 person-years). The patients with moderate [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.94] and high (HR 0.44, 95% CI 0.30-0.65) RGC had a lower risk of mortality than the low RGC group. Furthermore, even when restricted to a population with only UGS <1.0 m/s, the group with high RGC still had a lower risk of mortality than those with low RGC (HR 0.55, 95% CI 0.33-0.94). CONCLUSIONS: Lower RGC was independently associated with an increased risk of all-cause mortality among patients on HD; high RGC had a survival advantage even with a slow UGS.

Effects of anthropometric changes on hospitalization and mortality among patients on hemodialysis.

BACKGROUND: Low values for anthropometric indicators are risk factors for adverse clinical outcomes among patients on hemodialysis. Nonetheless, little is known about the association between the trajectory of anthropometric indicators and prognosis. We examined the association between a one-year change in anthropometric indicators and hospitalization and mortality in patients undergoing hemodialysis. METHODS: This retrospective cohort study collected data on five anthropometric indicators from patients undergoing maintenance hemodialysis: body mass index, mid-upper arm circumference, triceps skinfold, mid-arm muscle circumference, and calf circumference. We calculated their trajectories over one year. The outcomes were all-cause death and the number of all-cause hospitalizations. Negative binomial regressions were used to examine these associations. RESULTS: We included 283 patients (mean age, 67.3 years; 60.4% males). During the follow-up period (median, 2.7 years), 30 deaths and 200 hospitalizations occurred. Body mass index (incident rate ratio [IRR]: 0.87; 95% confidence interval [CI] 0.85-0.90), mid-upper arm circumference (IRR: 0.94; 95% CI 0.88-0.99), triceps skinfold (IRR: 0.92; 95% CI 0.84-0.99), and mid-arm muscle circumference (IRR: 0.99; 95% CI 0.98-0.99) increases over one year were associated with a lower risk of all-cause hospitalizations and death regardless of their value at any one point in time. However, the calf circumference trajectory was not associated with clinical events (IRR: 0.94; 95% CI 0.83-1.07). CONCLUSIONS: Body mass index, mid-upper arm circumference, triceps skinfold, and mid-arm muscle circumference trajectories were independently associated with clinical events. Routinely assessing these simple measures in clinical practice may provide additional prognostic information for managing patients undergoing hemodialysis.

Changes in body composition of patients undergoing hemodialysis during the coronavirus disease 2019 pandemic: a retrospective longitudinal study.

Background: The spread of coronavirus disease 2019 (COVID-19) has dramatically altered the lifestyles of many people worldwide. Several studies reported that body weight of young adults increased during the COVID-19 pandemic; however, weight loss has been observed in the elderly population. Therefore, trends in body composition due to the COVID-19 pandemic may vary depending on the characteristics of the population. This study aimed to investigate the changes in body mass index (BMI), muscle mass, and fat mass before and during the COVID-19 pandemic among patients undergoing hemodialysis. Methods: In this retrospective longitudinal study, we enrolled 115 clinically stable outpatients (mean age: 65.7 ± 11.2 years, 62.6% men) who underwent hemodialysis thrice a week. Baseline data were collected between April 2019 and March 2020, before the declaration of the COVID-19 emergency by the Japanese government. The follow-up measurements were performed between July 2020 and March 2021 during the COVID-19 pandemic. Patient characteristics, laboratory data, and BMI measurements were collected from the medical records. Muscle mass and fat mass were measured using bioelectrical impedance analysis. Results: BMI and fat mass among the study participants were significantly higher during the COVID-19 pandemic than before the pandemic (p < 0.01), but no significant change in muscle mass was observed. A restricted cubic spline function showed that the increase in BMI appeared to correlate well with fat mass, but not with muscle mass. Conclusions: BMI and fat mass of patients on hemodialysis significantly increased due to preventive measures against the COVID-19 pandemic in Japan. These findings may provide useful information in making nutritional management decisions for patients undergoing hemodialysis during and after the COVID-19 pandemic.

Physical function and physical activity in hemodialysis patients with peripheral artery disease.

INTRODUCTION: Peripheral artery disease (PAD) is commonly observed in patients undergoing hemodialysis. PAD impairs the vasculature and leads to pathophysiologic changes in the skeletal muscles, causing physical function impairment and physical inactivity in general. However, it is unclear whether PAD adversely affects physical function and physical activity in patients on hemodialysis. METHODS: We performed a cross-sectional study with a retrospective review of the data to determine whether PAD is associated with impaired physical function and physical activity in patients undergoing hemodialysis. The study population comprised 310 patients and 88 healthy subjects. PAD was diagnosed based on an ankle-brachial index of <1.00 in patients on hemodialysis. Measurements of physical function included maximum walking speed, muscle strength in the lower extremities, and balance while standing. FINDINGS: Of the 310 patients, 84 (27.1%) had PAD. When patients undergoing hemodialysis were divided into those without PAD and those with PAD, both groups had poorer physical function and physical activity than the healthy control subjects. After adjustments for potential confounders, it was found that patients on hemodialysis with PAD had slower walking speed, poorer standing balance, and less physical activity than those without PAD. However, there was no significant difference in lower extremity muscle strength between the two groups. DISCUSSION: PAD diagnosed based on an ankle-brachial index of <1.00 was independently associated with impaired physical function and reduced physical activity in patients undergoing hemodialysis.

Comparison of the association between six different frailty scales and clinical events in patients on hemodialysis.

BACKGROUND: Frailty is associated with adverse outcomes in patients undergoing hemodialysis (HD). However, no study has used various frailty assessments in patients on HD to examine their association with clinical events. In this study, we investigated the association between clinical events and six frailty scales. METHODS: Outpatients who underwent HD between 2018 and 2020 were retrospectively enrolled. Frailty was defined using the Fried Frailty Phenotype, Study of Osteoporotic Fractures (SOF) Index, Short Physical Performance Battery (SPPB), Frail Screening Index, FRAIL scale and Clinical Frailty Scale. Outcomes were clinical events, including a composite of multiple (i.e. recurrent) all-cause hospitalizations, fractures and/or all-cause mortality. The association of clinical events and the frailty scales were investigated using negative binomial regression analysis. RESULTS: Fried Frailty Phenotype [incident rate ratio (IRR), 1.62; 95% confidence interval (CI), 1.49-1.76], SOF Index (IRR, 1.42; 95% CI, 1.10-1.83), SPPB (IRR, 1.79; 95% CI, 1.11-2.88) and Clinical Frailty Scale (IRR, 1.65; 95% CI, 1.04-2.61) were significantly associated with clinical events. However, Frail Screening Index (IRR, 1.38; 95% CI, 0.60-3.18) and FRAIL scale (IRR, 1.30; 95% CI, 0.88-1.92) showed no significant association with clinical events. CONCLUSIONS: Objective frailty assessments (SPPB) and medical staff impression-based frailty (Clinical Frailty Scale) may be useful prognostic predictors for patients on HD. Questionnaire-based frailty assessment should be carefully considered when used as a measurement of frailty.

Trajectory of Serum Albumin Prior to Death in Patients Receiving Hemodialysis.

OBJECTIVE: Although some clinical expert guidelines recommend regular monitoring of serum albumin levels in patients undergoing maintenance hemodialysis, little is known about the serum albumin trajectory patterns over time, and it is unclear how the trajectory change before death. METHODS: We performed this retrospective study using data from 421 patients receiving hemodialysis in a dialysis facility. We divided patients into died and survived groups according to whether they died during the observation period. To compare the albumin trajectories during the observation period between the died and survived groups, linear mixed-effect models and a backward timescale from the year of death or study end were used. RESULTS: During the observation period (median, 5.1 years; maximum, 8.4 years), 115 patients receiving dialysis died. The serum albumin level showed steeper decline 3 years before death in the died group than in the survived group. The difference in albumin between the died and survived groups became apparent 3 years before death (difference, 0.08 g/dL; 95% confidence interval, 0.00-0.15 g/dL; P = .04), and the difference widened over time (difference at 1 year before death, 0.24 g/dL; 95% confidence interval, 0.14-0.33 g/dL; P < .001). Furthermore, in an analysis of albumin trajectories according to cause of death, the albumin level showed a downward trend regardless of the cause of death. CONCLUSION: The serum albumin trajectory differed between patients undergoing hemodialysis who died and who survived, supporting the importance of monitoring the albumin trajectory in clinical practice.

Simplified discriminant parameters for sarcopenia among patients undergoing haemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at an increased risk of developing sarcopenia, which can lead to various adverse health outcomes. Although the diagnosis of sarcopenia is essential for clinical management, it is not feasible in routine clinical practice for populations undergoing haemodialysis because it is time-consuming and resources are limited. Serum creatinine levels in patients with ESRD have been gaining attention as a screening parameter for sarcopenia because serum creatinine is a routinely measured byproduct of skeletal muscle metabolism. This study aimed to evaluate the discriminative ability of the creatinine-derived index for sarcopenia in patients undergoing haemodialysis. METHODS: We diagnosed sarcopenia according to the Asian Working Group for Sarcopenia (AWGS) 2 criteria in 356 clinically stable outpatients with ESRD enrolled from three dialysis facilities. We adopted the modified creatinine index as a simplified discriminant parameter for sarcopenia in addition to the calf circumference, SARC-F score, and combination of both (i.e. SARC-CalF score), which are recommended by the AWGS. Receiver operating characteristic analysis and logistic regression analysis were conducted to evaluate the discriminative ability of the modified creatinine index for sarcopenia. RESULTS: Of the study participants, 142 (39.9%) were diagnosed with sarcopenia. The areas under the curve of the modified creatinine index against sarcopenia in the male and female participants were 0.77 (95% confidence interval [CI]: 0.71 to 0.83) and 0.77 (95% CI: 0.69 to 0.85), respectively. All simplified discriminant parameters were significantly associated with sarcopenia, even after adjusting for patient characteristics and centre. In the comparison of the odds ratios for sarcopenia for 1-standard deviation change in the simplified discriminant parameters, the odds ratio of the modified creatinine index was 1.92 (95% CI: 1.15 to 3.19), which was lower than that of the calf circumference (odds ratio: 6.58, 95% CI: 3.32 to 13.0) and similar to that of the SARC-F (odds ratio: 1.57, 95% CI: 1.14 to 2.16) and SARC-CalF scores (odds ratio: 2.36, 95% CI: 1.60 to 3.47). CONCLUSIONS: This study revealed a strong association between the creatinine-derived index and sarcopenia in patients undergoing haemodialysis. The modified creatinine index was equal or superior to those of SARC-F and SARC-CalF score in discriminability for sarcopenia. However, the ability of the calf circumference to discriminate sarcopenia is extremely high, and further study is needed to determine whether it can be used to detect deterioration of muscle mass and function over time.

Associations between dynapenia, cardiovascular hospitalizations, and all-cause mortality among patients on haemodialysis.

BACKGROUND: Low muscle strength is associated with adverse clinical outcomes in patients undergoing haemodialysis (HD). No studies have reported the association between dynapenia, defined by both low handgrip strength (HGS) and quadriceps isometric strength (QIS), and long-term clinical outcomes in patients on HD. We examined the associations between dynapenia, cardiovascular (CV) hospitalizations, and all-cause mortality in the HD population. METHODS: This retrospective study used data from outpatients undergoing HD at two dialysis facilities between October 2002 and March 2020. We defined low muscle strength as an HGS of <28 kg for men and <18 kg for women and a QIS of <40% dry weight. Furthermore, we categorized dynapenia into three groups: robust ('high HGS and high QIS'), either low HGS or low QIS ('low HGS only' or 'low QIS only'), and dynapenia ('low HGS and low QIS'). The outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. Cox proportional hazards and negative binomial models were used to examine these associations. RESULTS: A total of 616 patients (mean age, 65.4 ± 12.2 years; men, 61%) were included in the analyses. During the follow-up (median, 3.0 years), a total of 163 deaths and 288 CV hospitalizations occurred. Patients with the either low HGS or low QIS [hazard ratio (HR), 1.75; 95% confidence intervals (CIs), 1.46-2.10] and dynapenia (HR, 2.80; 95% CIs, 2.49-3.14) had a higher risk of mortality than those in the robust group. When compared with the robust group, the either low HGS or low QIS [incidence rate ratio (IRR): 1.41, 95% CI: 1.00-1.99] and dynapenia (IRR: 2.04, 95% CI: 1.44-2.89) groups were associated with a significantly higher incident risk of CV hospitalizations. CONCLUSIONS: Dynapenia (muscle weakness in both upper and lower extremities) was associated with increased risks of all-cause mortality and CV hospitalizations among patients on HD. Screening for dynapenia using both HGS and QIS may be useful for prognostic stratification in the HD population.

Limitations of SARC-F as a Screening Tool for Sarcopenia in Patients on Hemodialysis.

INTRODUCTION: There are limited screening tools for sarcopenia in patients undergoing hemodialysis. This study aimed to investigate the reliability and validity of the SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls) questionnaire as a screening tool for sarcopenia (defined by the Asian Working Group for Sarcopenia [AWGS2019]) in patients undergoing hemodialysis. METHODS: This cross-sectional study enrolled 179 patients (mean age: 66.5 ± 12 years, 58% men) undergoing maintenance hemodialysis 3 times per week at a hemodialysis center in Japan. The SARC-F score, handgrip strength, usual gait speed, sit-to-stand test time, short physical performance battery (SPPB), and appendicular skeletal muscle mass were evaluated. The reliability and validity of the SARC-F were analyzed using receiver-operating characteristic curve, area under the curve (AUC), and sensitivity/specificity analyses. RESULTS: There were 49 (27.4%) patients with sarcopenia. Patients with SARC-F ≥4 (59 patients, 33.0%) had poorer grip strength, lower SPPB score, and slower gait speed than those with SARC-F <4, while the skeletal muscle mass index did not differ significantly between the two groups. The sensitivity and specificity values of the SARC-F for identifying sarcopenia were 42.9% and 70.8%, respectively, while those for identifying severe sarcopenia were 66.7% and 72.3%, respectively. The AUCs of SARC-F were 0.57 for sarcopenia and 0.70 for severe sarcopenia. DISCUSSION/CONCLUSION: The SARC-F alone is an inadequate screening tool for sarcopenia in patients undergoing hemodialysis. It should be used in combination with objective assessment measures, rather than as a first-step screening tool, to diagnose sarcopenia.

The effects of amino acid/protein supplementation in patients undergoing hemodialysis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: We evaluated the efficacy of the intervention consisting of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis. METHODS: This systematic review and meta-analysis identified potential studies through a systematic search of 4 electronic databases and references from eligible studies from database inception to August 2020. We included only randomized controlled trials reporting the efficacy of amino acid/protein supplementation on muscle mass, muscle strength and physical function in patients on hemodialysis. RESULTS: Of 6529 unique citation records, 4 studies including 243 participants were selected for inclusion in the meta-analysis. Although there were no significant differences in muscle mass and muscle strength between the intervention and control groups, amino acid/protein supplementation was shown to significantly improve physical function (shuttle walk, MD 32.7, 95% CI 21.7 to 43.7, P < 0.001; gait speed, MD 0.07, 95% CI 0.01 to 0.13, P = 0.02; timed up and go, MD -0.42, 95% CI -0.68 to -0.15, P = 0.002) in patients on hemodialysis. CONCLUSIONS: We confirmed the positive effect of amino acid/protein supplementation on physical function in people undergoing hemodialysis. However, there is still insufficient evidence, and more rigorously designed randomized controlled trials with high quality are needed.