Frailty and Duration of Maintenance Dialysis: A Japanese Nationwide Cross-Sectional Study.

RATIONALE & OBJECTIVE: Prolonged end-stage kidney disease (ESKD) is a risk factor for frailty and the number of patients in Japan receiving maintenance dialysis for more than 20 years is large and growing. This study aimed to characterize the association of dialysis vintage and frailty among patients receiving dialysis in Japan. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Patients with ESKD aged over 50 years of age who received maintenance dialysis in 2018 as represented in the JSDT Renal Data Registry database (n=227,136). EXPOSURES: Dialysis vintage categorized as: 0-<5 years, 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years. OUTCOMES: The frailty and bedridden status were defined as graded ≥2 and graded 4, respectively, according to the Eastern Cooperative Oncology Group Performance Status scale. ANALYTICAL APPROACH: Poisson regression models with robust error variance adjusted for potential covariates were used to estimate the adjusted prevalence ratios (aPRs) for frailty and bedridden status. Clinical characteristics of patients undergoing dialysis for ≥ 30 years were also described. RESULTS: Among the study cohort, 5510 patients (2.4%) had been undergoing dialysis for 30 years or more. The prevalence of frailty in the group with over 30 years of dialysis history was 36.2%, while the rate of being bedridden was 6.4%. Compared to <5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with frailty (aPRs [95% confidence intervals]: 1.06 [1.05-1.08], 1.10 [1.08-1.11], 1.14 [1.10-1.17], and 1.67 [1.60-1.73]), respectively. Compared to <5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with being bedridden (aPRs [95% confidence intervals]: 1.17 [1.13-1.22], 1.26 [1.20-1.31], 1.17 [1.08-1.26], and 1.66 [1.49-1.86], respectively. LIMITATIONS: Patients receiving short-term dialysis may have more unmeasured comorbidities compared to patients receiving long-term dialysis. CONCLUSIONS: Long-term dialysis therapy, particularly exceeding 30 years, is associated with deterioration of physical function and frailty.

Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study.

BACKGROUND: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. METHODS: Study design: cohort study. SETTING: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. PREDICTOR: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. OUTCOMES: all-cause mortality and hospitalization during the mean 2.8-year follow-up. MEASUREMENTS: hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. RESULTS: The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. CONCLUSIONS: PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.

Synergic Impact of Body Mass Index, Diabetes, and Age on Long-Term Mortality in Japanese Incident Hemodialysis Patients: A Cohort Study on a Large National Dialysis Registry.

OBJECTIVES: The relationships among body mass index (BMI), diabetes, age, and all-cause mortality in hemodialysis patients remain unclear. We examined BMI-stratified relationships between diabetes, age, and the risk of long-term mortality in incident hemodialysis patients. METHODS: This is a cohort study. Data were obtained from the national dialysis registry in Japan 2007 that included 35,415 incident hemodialysis patients and 6,061 patients aged ≥20 years with BMI data. Patients were divided into 6 categories according to baseline BMI (low: <18.5, normal: 18.5-25, Obesity: ≥25) and the presence or absence of diabetes. The primary outcome was all-cause mortality during a 5-year follow-up. Hazard ratios were estimated using Cox's model for the relationships among diabetes, BMI categories, and all-cause mortality, and adjusted for potential confounders. Patients with a normal BMI and non-diabetic were the reference category. We also examined the effects of age on these relationships. RESULTS: A total of 6,061 patients, including 3,239 with diabetes, were enrolled. During the follow-up, 31.0% and 30.7% of all and diabetic patients, respectively, died. Cox's regression analysis showed that low BMI, but not obesity, was independently associated with an increased risk of all-cause death in patients with and without diabetes. When patients were divided into 2 groups-younger and older than 60 years-the risk of mortality in both groups was increased in low BMI with diabetes. CONCLUSIONS: Among Japanese incident hemodialysis patients, low BMI increases the risk of all-cause mortality. The markedly high mortality rate in diabetic patients with low BMI regardless of age warrants attention.

Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study.

BACKGROUND/AIMS: Uric acid (UA) levels are affected by changes in dialysis; however, the relationship between the pre- and postdialysis UA difference (UAD) and mortality remains unclear. METHODS: A total of 1,073 patients receiving maintenance hemodialysis (HD) were enrolled in this cohort study and followed up for 5 years. Patients were divided into quartile categories according to baseline UAD. Cox's regression analyses were used to investigate the relationship between UAD categories and all-cause and cardiovascular (CV) mortalities while adjusting for potential confounders. RESULTS: A total of 280 patients died of all causes, including 121 CV deaths, during the follow-up. In the analysis for all-cause mortality, hazard ratios were significantly higher in the lowest UAD group (< 4.7 mg/dL) than in the highest UAD group (> 6.2 mg/dL). A correlation was not observed with CV mortality. CONCLUSION: UAD correlated with all-cause mortality. UAD may be the most appropriate reference for controlling UA in HD patients.

N-terminal-pro-B-type-natriuretic peptide associated with 2-year mortality from both cardiovascular and non-cardiovascular origins in prevalent chronic hemodialysis patients.

N-terminal-pro-B-type-natriuretic peptide (NT-proBNP) was a predictive marker of cardiovascular disease (CVD)-related death in chronic dialysis patients. NT-proBNP was also correlated with markers of inflammation, malnutrition and protein-energy wasting. We hypothesized whether NT-proBNP was also associated with non-CVD death in chronic dialysis patients. A prospective observational study for incidence of death in chronic dialysis patients was conducted. Prevalent chronic dialysis patients (n = 1310) were enrolled and followed for 24 months. One hundred forty-four deaths were recorded. Area under the curve using ROC analysis for NT-proBNP showed: all causes of death (0.761), CVD-related (0.750), infection and malignancy-related (0.702) and others and unknown (0.745). After adjusting for age, sex, hemodialysis vintage, cardiothoracic ratio, mean pre-dialysis systolic blood pressure, dry weight and basal kidney disease, the hazard ratios (95% confidence intervals) per 1-log NT-proBNP calculated using multivariate Cox analysis were: all causes of death, 3.83 (2.51-5.85); CVD-related, 4.30 (2.12-8.75); infection and malignancy-related, 2.41 (1.17-4.93); and others and unknown origin, 5.63 (2.57-12.37). NT-proBNP was significantly associated not only with CVD-relate but also with non-CVD-related deaths in this population of prevalent chronic dialysis patients.

Risk of Cerebral Infarction in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study (MID study).

BACKGROUND/AIMS: Predictors including the preventive effects of antiplatelet and anticoagulant drugs on cerebral infarction (CI) events have not yet been clarified in dialysis patients. The aim of the present study was to examine the risk of CI and preventive effects of these drugs in Japanese hemodialysis patients. METHODS: Patients receiving maintenance hemodialysis (n=1,551, median age (interquartile range), 69.0 (59.0-78.0) years; 41.5% female) were enrolled in the Miyazaki Dialysis Cohort Study and prospectively followed-up for 3 years. Kaplan-Meier and Cox's regression analyses were used to clarify the risk of CI. RESULTS: Eighty-four patients developed CI at an incidence of 21.5/1000 patients per year. The presence of a previous history of CI, atrial fibrillation (AF), and diabetes mellitus in addition to age were also identified as predictive factors for new CI, whereas no relationship was observed between antiplatelet and/or anticoagulant usage and CI. Furthermore, no significant difference was noted in the frequency of CI events between patients with AF who received warfarin and those who did not. CONCLUSIONS: The incidence of CI was higher in dialysis patients with a previous history of CI and AF; however, the preventive effects of antiplatelet/anticoagulant drugs on the development of CI were not evident.

Glycaemic control is a predictor of infection-related hospitalization on haemodialysis patients: Miyazaki Dialysis Cohort study (MID study).

AIM: Although infection is the second leading cause of death in maintenance haemodialysis patients, the effects of glycaemic control on infection in diabetic haemodialysis patients have not yet been examined in detail. We examined the relationship between diabetes or glycemic control and infection-related hospitalization (IRH) in haemodialysis patients. METHODS: Patients receiving maintenance haemodialysis (n = 1551, 493 diabetic patients) were enrolled in this prospective cohort study in December 2009 and followed-up for 3 years. IRH during the follow-up period was abstracted from medical records. Kaplan-Meier and Cox regression analyses were used to investigate the relationship between diabetes or glycaemic control and IRH. RESULTS: The Kaplan-Meier analysis revealed that the risk of IRH was significantly higher in haemodialysis patients with diabetes, particularly in those with poorly controlled HbA1c levels (HbA1c ≥ 7.0%), than in haemodialysis patients without diabetes. When patients with ≥HbA1c 7.0% were divided into two groups using a median value of HbA1c, the risk of IRH was significantly higher in those with the poorest glycaemic control (HbA1c ≥ 7.4%), an older age, or lower albumin levels. The multivariable-adjusted hazard ratio for the risk of IRH was not higher in the second criteria of HbA1c (HbA1c 7.0-7.3%), but was significantly higher in the group with the poorest glycaemic control (HbA1c ≥ 7.4%) than in those in the good control criterion (HbA1c < 7.0%). CONCLUSIONS: Although diabetes is a risk factor for IRH among maintenance haemodialysis patients, the relationship between glycaemic control and the risk of infection is not linear. Therefore, the risk of infection may increase in a manner that is dependent on the glycaemic control threshold.

Prognostic Implication of Three-Dimensional Mitral Valve Tenting Geometry in Dilated Cardiomyopathy.

BACKGROUND AND AIM OF THE STUDY: Functional mitral regurgitation (FMR) is a clinically important complication of left ventricular (LV) dysfunction, occurring as a result of geometric deformity in the mitral valve (MV) complex. The study aim was to determine whether tenting parameters derived from real-time three-dimensional echocardiography (RT3DE) can predict the long-term prognosis for patients with dilated cardiomyopathy (DCM). METHODS: Mitral valve tenting morphology, LV volume and function, and papillary muscle positions were monitored using transthoracic RT3DE in 75 subjects (66 with DCM, nine controls). The maximum tenting sites of the leaflet (maxTS) were also mapped from the reconstructed 3D images, to determine if the 3D tenting parameters correlated to long-term outcome. RESULTS: Follow up information was collected from 62 patients with DCM over a mean period of 42 +/- 31 months. Cardiovascular events occurred in 30 patients (48%), including 13 cardiac deaths (21%). The patients were allocated to an Event group (n = 30) or a Non-event group (n = 32). The LV volumes were significantly larger and LV ejection fraction was lower in the Event group compared to the Non-event group. The 3D tenting volumes were significantly larger in the Event group than the Non- event group (p = 0.05). The maxTS were positioned mostly in the middle portion of the anterior mitral leaflet in the Non-event group (maxTS-mid AML), but in the Event group they were mostly found in the MV coaptation region of the leaflet (maxTS-coapt) (p <0.001). Patients with maxTS-coapt had a worse prognosis compared to those with maxTS-mid AML. On multivariate Cox regression analysis, maxTS was the strongest predictor of event-free survival. CONCLUSION: The 3D tenting pattern, assessed with RT3DE, would be an important clinical parameter in predicting long-term prognosis in patients with DCM.

A randomized control study on the procedure for switching epoetin beta (EPO) to epoetin beta pegol (CERA) in the treatment of renal anemia in maintenance hemodialysis patients.

BACKGROUND/AIMS: We investigated the method of switching EPO to CERA that does not cause a decrease in the Hb level. METHODS: Fifty EPO-treated patients were randomly divided into two groups in which CERA was administered every two weeks (Q2W) or every four weeks (Q4W). After 8 weeks of treatment, the frequency of administration was changed to Q4W in the former. Follow-up was performed for 24 weeks. RESULTS: There was no difference in the Hb level between the two groups until 6 weeks. In the Q2W group, the Hb maintained a stable level throughout a study period. However, in the Q4W group, the Hb level was significantly lower than in the Q2W group at weeks 9, 11, and 13. CONCLUSION: EPO switching to CERA without a decrease in the Hb level could be achieved by administering CERA every two weeks, but not every four weeks, for a specific period after switching.

[Clinical characteristics of patients with IgA nephropathy and long-term survival after dialysis therapy].

BACKGROUND AND OBJECTIVES: Little is known about the treatment and clinical status of patients with biopsy-proven IgA nephropathy (IgAN) during long-term maintenance dialysis. METHODS: Fifty-two of 433 patients with IgAN who had favorable survival rates of 93.3% and 65.1% at 10 and 20 years, respectively, in a previous study and had reached end-stage kidney disease were followed up for 11.1 ± 6.2 years. Forty of the 52 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) at the final observation in February 2012 were eligible for entry in this study. Laboratory findings, treatments and complications during the long-term follow-up were analyzed. RESULTS: Mean age at starting dialysis (HD, n = 39; PD, n = 1) was 44.2 ± 13.1 years. Vascular access was achieved through an arteriovenous fistula in 95% of the 39 patients. Prescription rates of anti-hypertensive agents (68%), anti-platelet agents (35%), and statins (15%) were relatively low. The cardiothoracic ratio was well-controlled (< 50%) in about 60% of all patients and mean values for hemoglobin (10.6 ± 1.31 g/dL), adjusted calcium (9.56 ± 0.81 mg/dL), phosphate(5.89 ± 1.64 mg/dL), and intact-PTH (186 ± 221 pg/mL) were within the treatment goals recommended by Japanese guidelines. Complications during follow-up comprised cardiovascular events (n = 11), malignancy (n = 4), diabetes (n = 2), and arterial fibrillation (n = 2). Patients who remained on dialysis for > 10 years (n = 22) had started dialysis when they were significantly younger, and had a higher rate of onset of malignancy and of intact PTH values than those who were on dialysis for < 10 years (n = 18). CONCLUSIONS: Patients with IgAN who remain on dialysis over the long-term can maintain stable and favorable clinical findings although the occurrence of malignant complications and bone mineral metabolic disorder should be monitored.

Effect of atherosclerosis on the relationship between atrial fibrillation and ischemic stroke incidence among patients on hemodialysis.

In patients undergoing hemodialysis, the impact of atrial fibrillation (AF) through cardiac thromboembolism on the development of ischemic stroke may be influenced by the severity of atherosclerosis present. However, there are no large-scale reports confirming whether the severity of atherosclerosis influences the relationship between AF and stroke development in patients requiring hemodialysis. We aimed to investigate the effects of atherosclerotic disease on the relationship between AF and new-onset ischemic stroke. This nationwide longitudinal study based on dialysis facilities across Japan used data collected from the Japanese Renal Data Registry at the end of 2019 and 2020. The exposure was AF at the end of 2019, identified using a resting 12-lead electrocardiography. The primary outcome was the incidence of cerebral infarction (CI) after 1 year. To examine whether the number of atherosclerotic diseases modified the association between AF and the outcome, we estimated the odds ratios (ORs) using a logistic regression model and then assessed the presence of global interaction using Wald test. Following the study criteria, data from 151,350 patients (mean age, 69 years; men, 65.2%; diabetic patients, 48.7%) were included in the final analysis. A total of 9841 patients had AF (prevalence, 6.5%). Between 2019 and 2020, 4967 patients (3.2%) developed ischemic stroke. The adjusted OR of AF for new-onset CI was 1.5, which showed a decreasing trend with an increasing number of atherosclerotic diseases; the interaction was not significant (P = 0.34). While age, diabetes mellitus, smoking, systolic blood pressure, and serum C-reactive protein concentration were positively associated with CI, intradialytic weight gain, body mass index, and serum albumin level were negatively associated. While we demonstrated the association between AF and new-onset CI among Japanese patients on hemodialysis, we failed to demonstrate the evidence that the association was attenuated with an increasing numbers of atherosclerotic complications.

Impact of Dysmagnesemia on Atrial Fibrillation in Maintenance Hemodialysis Patients: A Nationwide Study.

INTRODUCTION: The dose-response relationship between serum magnesium (sMg) and atrial fibrillation (AF) and the contribution of dysmagnesemia to AF among hemodialysis patients remain unknown. Hence, we examined the dose-response correlation between sMg and AF and estimated the extent of the contribution of dysmagnesemia to AF in this population. METHODS: This was a nationwide cross-sectional study on the Japanese Society for Dialysis Therapy registry, also known as Japanese Renal Data Registry (JRDR), encompassing a nationwide population of dialysis centers, as of the end of 2019. Eligible participants were adult patients undergoing hemodialysis three times per week. The main exposure was sMg, categorized into seven categories (≤1.5, >1.5-≤2, >2-≤2.5, >2.5-≤3, >3-≤3.5, >3.5-≤4, and ≥4.0 mg/dL). The outcome was AF reported by dialysis facilities. The independent contribution to AF was assessed via logistic regression to generate population-attributable fractions, assuming a causal relationship between sMg and AF. RESULTS: Total 165,926 patients from 2,549 facilities were investigated. AF prevalence was 7.9%. Compared with the reference (>2.5-≤3 mg/dL), lower sMg was associated with increased AF (adjusted odds ratios (ORs) (95% confidence interval, CI) of 1.49 (1.19-1.85), 1.24 (1.17-1.32), and 1.11 (1.06-1.16) for sMg of ≤1.5, >1.5-≤2.0, and >2.0-≤2.5 mg/dL categories, respectively). Elevated sMg was associated with fewer AF (adjusted OR 0.87 [95% CI, 0.79-0.96] for sMg of >3.0-≤3.5 mg/dL). The adjusted population-attributable fraction of lower sMg and higher and lower sMg for AF was 7.4% and 6.9%, respectively. An association did indeed exist between lower sMg and AF, with the lowest percentages of AF at sMg levels above the reference range for the general population. CONCLUSION: Dysmagnesemia may be an important contributor to AF among adult hemodialysis patients. Further, longitudinal studies are warranted to determine whether sMg correction reduces the AF incidence.

Trust, Multidimensional Health Literacy, and Medication Adherence among Patients Undergoing Long-Term Hemodialysis.

BACKGROUND: Basic health literacy and trust in physicians can influence medication adherence in patients receiving dialysis. However, how high-order health literacy is associated with medication adherence and how trust in physicians mediates this association remain unclear. We assessed the inter-relationships between health literacy, trust in physicians, and medication adherence. We investigated the mediating role of trust in physicians in the relationship between health literacy and medication adherence. METHODS: This multicenter cross-sectional study included Japanese adults receiving outpatient hemodialysis at six dialysis centers. Multidimensional health literacy was measured using the 14-item Functional, Communicative, and Critical Health Literacy scale. Trust in physicians was measured using the five-item Wake Forest Physician Trust scale. Medication adherence was measured using the 12-item Adherence Starts with Knowledge scale. A series of general linear models were created to analyze the associations between health literacy and Adherence Starts Knowledge scores with and without trust in physicians. Mediation analysis was performed to determine whether trust in physicians mediated this association. RESULTS: In total, 455 patients were analyzed. Higher functional and communicative health literacies were associated with less adherence difficulties (per 1-point higher: -1.79 [95% confidence interval (CI): -2.59 to -0.99] and -2.21 [95% CI: -3.45 to -0.96], respectively), whereas higher critical health literacy was associated with greater adherence difficulties (per 1-point higher: 1.69 [95% CI: 0.44 to 2.94]). After controlling for trust in physicians, the magnitude of the association between health literacies and medication adherence decreased. Trust in physicians partially mediated the association between functional or communicative health literacy and medication adherence (especially beliefs) and completely mediated the association between critical health literacy and medication adherence (especially behaviors). CONCLUSIONS: Functional and communicative health literacies were positively associated with medication adherence, whereas critical health literacy was negatively associated with it. Each association was mediated by trust in physicians.

Long-term survival of patients with IgA nephropathy after dialysis therapy.

BACKGROUND/AIMS: How dialysis affects the survival of patients with biopsy-proven IgA nephropathy (IgAN) is not fully understood. The present long-term cohort study quantifies the survival rates and incidence of cardio-cerebrovascular diseases (CCVDs) among such patients in Japan. METHODS: Fifty-two of 433 patients with IgAN who had reached end-stage kidney disease underwent renal replacement therapy (RRT) between 1981 and 2010. The overall survival rate and incidence of CCVDs in these patients were evaluated during follow-up for 11.3 ± 6.4 years. RESULTS: The mean age at starting RRT was 42.8 ± 13.3 years. Only seven patients died during follow-up (mortality rate, 1.2/100 person-years) and Kaplan-Meier analysis revealed favorable survival rates of 93.3% and 65.1% at 10 and 20 years, respectively, compared with that of patients with glomerulonephritis in the registry of the Japanese Society for Dialysis Therapy who required RRT. Malignancy and CCVDs were causes of death at 13.6 ± 4.8 and 3.9 ± 1.3 years, respectively, after starting RRT. Fatal and non-fatal CCVDs developed in 15 (incidence, 2.7/100 person-years) patients and acute coronary syndrome and cerebral hemorrhage developed relatively soon after starting RRT. Cox proportional hazards models revealed that age at the time of starting RRT was a significant factor affecting the onset of CCVDs. Meanwhile, a history of having had corticosteroid as an initial treatment did not affect the onset of events. CONCLUSION: Although the survival of patients with IgAN is favorable after dialysis, the onset of CCVDs during the early phase of dialysis should be carefully monitored.

Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study.

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI-estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI-all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.

Effects of Bovine Lactoferrin on the Maintenance of Respiratory and Systemic Physical Conditions in Healthy Adults-A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: We investigated the effects of bovine lactoferrin (LF) on the maintenance of the respiratory and systemic physical conditions. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Healthy adults at Kyushu University of Health and Welfare ingested a placebo or bovine LF (200 mg/day) for 12 weeks. The primary endpoints were the total respiratory and systemic symptom scores. The secondary endpoint was the activity of plasmacytoid dendritic cells (pDCs) in peripheral blood. RESULTS: A total of 157 subjects were randomized (placebo, n = 79; LF, n = 78), of whom, 12 dropped out. The remaining 145 participants were included in the full analysis set (placebo group, n = 77; LF group, n = 68). The total scores for respiratory and systemic symptoms during the intervention were significantly lower in the LF group than in the placebo group. The expression of CD86 and HLA-DR on pDCs was significantly higher in the LF group than in the placebo group at week 12. Adverse events were comparable between the groups, and no adverse drug reactions were observed. CONCLUSIONS: These results suggest that orally ingested LF supports the normal immune system via maintaining pDC activity, and maintains respiratory and systemic physical conditions in healthy adults.

Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study.

BACKGROUND: Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out. METHODS: After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses. RESULTS: The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease. CONCLUSION: LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

Takotsubo cardiomyopathy after vaccination for coronavirus disease 2019 in a patient on maintenance hemodialysis.

Coronavirus disease-2019 (COVID-19) has affected more than 220 million individuals since the global pandemic began. There is an urgent need for safe and effective vaccines, and vaccinations, such as mRNA vaccines, have been initiated worldwide. However, the adverse effects of these vaccines remain unclear. We herein present a case of an 80-year-old female on maintenance hemodialysis who developed takotsubo cardiomyopathy 4 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. There was no obvious trigger for the onset of takotsubo cardiomyopathy other than the COVID-19 vaccination, which was the most significant event preceding her presentation. Echocardiograms obtained during her admission allowed us to monitor and show the recovery of left ventricular wall motion. We confirmed the diagnosis of takotsubo cardiomyopathy based on the findings, including transient left ventricular dysfunction, electrocardiographic abnormalities, an elevated troponin level, and the absence of occlusive coronary artery disease. In the present case, the vaccination may have triggered emotional or physical stress. Although difficulties are associated with proving the causal relationship in the present case, the temporal relationship between the vaccination and the onset of takotsubo cardiomyopathy is highly suggestive. The adverse effects associated with the vaccine are typical of COVID-19 vaccines administered to date, most of which are acceptable. Therefore, despite our experience of the present case, we still recommend the vaccination for COVID-19 because takotsubo cardiomyopathy induced by the COVID-19 vaccine is extremely rare and the prognosis of the patient was good. We herein present the first case of a patient on hemodialysis who developed takotsubo cardiomyopathy after receiving COVID-19 vaccination.

Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients.

BACKGROUND: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. METHODS: This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. RESULTS: Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. CONCLUSION: Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.