Japanese Dialysis Patients Research Articles

Cellular and humoral immune responses to COVID-19 booster vaccination in Japanese dialysis patients.

Dialysis patients are susceptible to developing severe coronavirus disease 2019 (COVID-19) due to hypoimmunity. Antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) after the primary vaccinations are lower in hemodialysis (HD) patients than in healthy individuals. This study aimed to evaluate the effect of a SARS-CoV-2 booster vaccination in HD and peritoneal dialysis (PD) patients based on antibody titers and cellular and humoral immunity. Participants of the control, HD, and PD groups were recruited from 12 facilities. SARS-CoV-2 antigen-specific cytokine and IgG-antibody levels were measured. Regulatory T cells and memory B cells were counted using flow cytometry at 6months after primary vaccination with BNT162b2 and 3weeks after the booster vaccination in HD and PD patients and compared with those of a control group. Booster vaccination significantly enhanced the levels of antibodies, cytokines, and memory B cells in three groups. The HD group showed significantly higher levels of IgG-antibodies, IL-1β, IL-2, IL-4, IL-17, and memory B cells than those in the control group at 3weeks after the booster dose. The PD group tended to show similar trends to HD patients but had similar levels of IgG-antibodies, cytokines, and memory B cells to the control group. HD patients had significantly stronger cellular and humoral immune responses than the control 3weeks after the booster dose. Our findings will help in developing better COVID-19 vaccination strategies for HD and PD patients.

Impact of COVID-19 versus other pneumonia on in-hospital mortality and functional decline among Japanese dialysis patients: a retrospective cohort study

Coronavirus disease 2019 (COVID-19) affects both life and health. However, the differentiation from other types of pneumonia and effect of kidney disease remains uncertain. This retrospective observational study investigated the risk of in-hospital death and functional decline in ≥ 20% of Barthel Index scores after COVID-19 compared to other forms of pneumonia among Japanese adults, both with and without end-stage kidney disease (ESKD). The study enrolled 123,378 patients aged 18 years and older from a national inpatient administrative claims database in Japan that covers the first three waves of the COVID-19 pandemic in 2020. After a 1:1:1:1 propensity score matching into non-COVID-19/non-dialysis, COVID-19/non-dialysis, non-COVID-19/dialysis, and COVID-19/dialysis groups, 2136 adults were included in the analyses. The multivariable logistic regression analyses revealed greater odds ratios (ORs) of death [5.92 (95% CI 3.62–9.96)] and functional decline [1.93 (95% CI 1.26–2.99)] only in the COVID-19/dialysis group versus the non-COVID-19/non-dialysis group. The COVID-19/dialysis group had a higher risk of death directly due to pneumonia (OR 6.02, 95% CI 3.50–10.8) or death due to other diseases (OR 3.00, 95% CI 1.11–8.48; versus the non-COVID-19/non-dialysis group). COVID-19 displayed a greater impact on physical function than other types of pneumonia particularly in ESKD.

Perspectives on the optimal timing of advance care planning among Japanese patients undergoing dialysis and clinicians: a cross-sectional study.

The majority of dialysis patients and clinicians favor early advance care planning in our sample. Yet, there is a disconnect: only 11% of patients discussed future care with their clinicians. Our findings indicate Japanese dialysis patients and clinicians support proactive advance care planning at or before dialysis initiation. Little is known about the optimal timing of discussions about advance care planning among dialysis patients and clinicians engaged in dialysis care. We aimed to explore the preferred timing for advance care planning and assess actual participation in advance care planning among dialysis patients and their clinicians. A scenario-based survey on Japanese patients aged ≥65years on dialysis and clinicians involved in their dialysis care was performed. Participants were asked if they would feel prepared to engage in advance care planning with their clinicians, offering a choice among four hypothetical stages within the illness trajectory, extending from the initiation of dialysis to a later phase characterized by the patient's extreme frailty. Overall, 181 patients and 128 clinicians participated in the study. Among these, 131 (72%) patients, and 84 (66%) clinicians indicated that they would prefer to initiate advance care planning around the time of dialysis initiation. Only 20 patients (11%) indicated that they had participated in advance care planning with at least one clinician, including 11 (6%) who indicated that they had discussed their preferences around life-sustaining treatments and 8 (4%) who had discussed their preferences around dialysis continuation. While fewer than 11% of patients undergoing dialysis and their clinicians enrolled in our study had participated in advance care planning, most indicated that they would be comfortable initiating the discussion around the time of dialysis initiation. These findings suggest untapped opportunities to engage patients in advance care planning early in the course of their dialysis.

Serum oxalate concentration is associated with coronary artery calcification and cardiovascular events in Japanese dialysis patients

Coronary artery calcification (CAC) is associated with cardiovascular disease (CVD). CAC might contain calcium oxalate, and a high serum oxalate (SOx) concentration is associated with cardiovascular mortality in dialysis patients. We assessed the associations between SOx and CAC or CVD events in Japanese hemodialysis patients. This cross-sectional and retrospective cohort study was done in 2011. Seventy-seven hemodialysis patients’ Agatston CAC score was measured, and serum samples were collected. SOx concentrations were measured in 2021 by using frozen samples. Also, new-onset CVD events in 2011–2021 were retrospectively recorded. The association between SOx concentration and CAC score ≥ 1000, and new-onset CVD events were examined. Median SOx concentration and CAC score were 266.9 (229.5–318.5) µmol/L and 912.5 (123.7–2944), respectively. CAC score ≥ 1000 was associated with SOx [adjusted odds ratio (OR) 1.01, 95% confidence interval (CI), 1.00–1.02]. The number of new-onset CVD events was significantly higher in patients with SOx ≥ median value [hazard ratio (HR) 2.71, 95% CI 1.26–6.16]. By Cox proportional hazard models, new-onset CVD events was associated with SOx ≥ median value (adjusted HR 2.10, 95% CI 0.90–4.91). SOx was associated with CAC score ≥ 1000 and new-onset CVD events in Japanese hemodialysis patients.

Comparison of therapeutic strategies for aortic stenosis between transcatheter and surgical aortic valve implantation: a retrospective cohort study in Japanese dialysis patients

BackgroundAlthough transcatheter aortic valve implantation (TAVI) is assumed to be a less invasive therapy in high-risk patients with aortic valve stenosis (AS), there have been limited data suggesting its beneficial effects on cardiovascular mortality in Japanese patients receiving dialysis therapy.MethodsHemodialysis patients with severe AS underwent either TAVI (n = 33) or surgical aortic valve replacement (SAVR, n = 25). We compared the postoperative outcomes and perioperative complications, including dialysis-associated parameters [e.g., intradialytic hypotension (IDH)], between TAVI and SAVR.ResultsA 30-day and 1-year mortality rate was nearly the same among the TAVI and the SAVR group. Incidence of permanent pacemaker implantation or other events, including stroke, bleeding and vascular complications, in the TAVI group were not different from those in SAVR patients during the 30-day or 1-year postoperative period. The incidence of IDH was increased following SAVR (odds ratio (OR) = 11.29 [95% CI 1.29–98.89]) but was not affected by TAVI (OR = 1.55 [95% CI 0.24–9.94]). Among the patients aged 75 or older, the incidence of IDH was particularly conspicuous in the SAVR group (OR = 15.75 [95% CI 2.30–107.93]). Because there were differences in background data (age, EuroSCORE II, and dialysis duration) between these groups, propensity score-matched analysis was conducted and showed no difference in the composite event-free probability between the TAVI and the SAVR group over one year (p = 0.816).ConclusionsTAVI offers an alternative strategy to Japanese hemodialysis patients with severe AS, with nearly the same incidence of complications as SAVR during 1-year observation.

Efficacy of molnupiravir and sotrovimab in Japanese dialysis patients with COVID-19 in clinical practice during the Omicron (BA.1 and BA.2) pandemic.

In the present study, the efficacy of sotrovimab and molnupiravir in dialysis patients with COVID-19 was investigated using a registry of COVID-19 in Japanese dialysis patients. Dialysis patients with confirmed SARS-CoV-2 during the COVID-19 (Omicron BA.1 and BA.2) pandemic were analyzed. Patients were classified into four treatment groups: molnupiravir monotherapy (molnupiravir group), sotrovimab monotherapy (sotrovimab group), molnupiravir and sotrovimab combination therapy (combination group), and no antiviral therapy (control group). The mortality rates in the four groups were compared. A total of 1480 patients were included. The mortality of the molnupiravir, sotrovimab, and combination groups were significantly improved compared to the control group (p < 0.001). Multivariate analysis indicated that antiviral therapy improves the survival of dialysis patients with COVID-19 (hazard ratio was 0.184 for molnupiravir, 0.389 for sotrovimab, and 0.254 for combination groups, respectively). Sotrovimab showed efficacy in Omicron BA.1 but attenuated in BA.2. Molnupiravir also showed efficacy in BA.2, suggesting administration of molnupiravir would be important.

PS-C03-5: REAL-WORLD DATA OF BLOOD PRESSURE IN DIALYSIS PATIENTS WITH AND WITHOUT DIABETES IN JAPAN USING THE WEB-BASED DATABASE

Objective: Diabetic nephropathy was the most common primary disease among patients undergoing dialysis, and the number is growing each year. Despite advancements in dialysis technique, cardiovascular complications and mortality in dialysis patients with diabetes remain higher than in those without diabetes. Furthermore, hypertension is commonly known to contribute to the development of cardiovascular complications in dialysis patients, and we aimed to compare the systolic blood pressure (SBP) in dialysis patients with and without diabetes using the Web-based Analysis of Dialysis Data Archives (WADDA) system database. Design and Methods: From 2014 to 2020, we enrolled dialysis patients who had their predialysis SBP measured using the WADDA system 2.1. We classified SBP and evaluated its trends over time by gender, age, and presence of diabetes using the Japanese Society of Hypertension guidelines 2019 (JSH2019). Furthermore, we looked at the relationship between SBP and cardiovascular death in patients with and without diabetes. Results: Dialysis patients with diabetes (n = 168,227) had a mean age of 69.2 (11.7) years versus 69.4 (13.3) years, a mean predialysis history of 5.5 (5.3) years versus 9.4 (9.3 years), and a mean dialysis SBP of 156.6 (25.0) mmHg versus 147.9 (23.6) mmHg, respectively. Dialysis patients with diabetes had higher rates of cardiovascular complications than those without diabetes. From 2014 to 2020, the percentage and absolute values of hypertension were higher in dialysis patients with diabetes than across all age groups and in both men and women. Patients with cerebrovascular death had a higher rate of hypertension, but there was no difference in the rate of grade I and II hypertension between the two groups. Conclusion: We summarized the recent trends in SBP of Japanese dialysis patients with and without diabetes using the WADDA system. Dialysis patients with diabetes had higher SBP than those without diabetes in all age groups and in both men and women. As a result, optimal blood pressure management for dialysis patients with and without diabetes is important for the prevention of cerebrovascular death.

PS-C03-4: THE REAL WORLD TRENDS IN BLOOD PRESSURE OF DIALYSIS PATIENTS IN JAPAN USING THE WEB-BASED DATABASE

Objective: Hypertension is common in dialysis patients, which is frequent as well as poorly controlled. Blood pressure (BP) has a J curve relationship with cardiovascular disease and survival in dialysis patients; however, optimal BP is not well defined. We wanted to learn about the clinical characteristics of Japanese patients undergoing dialysis and the prevalence of cardiovascular death based on systolic blood pressure (SBP) using the Web based Analysis of Dialysis Data Archives (WADDA) system database. Design and Methods: We enrolled the patients undergoing dialysis who were recorded pre dialysis SBP from 2012 to 2020 using WADDA system 2.1. According to the Japanese Society of Hypertension guidelines 2019 (JSH 2019), we classified SBP and evaluated their trends over time by gender and age. Moreover, we evaluated the association between SBP and cardiovascular death. Results: Using the 2020 database, we looked at 336,759 Japanese patients undergoing dialysis (222,510 men and 114,249 women). The mean age was 69.4 ± 12.5 years, the mean dialysis history was 7.4 ± 7.7 years, and the mean pre dialysis SBP was 152.3 ± 24.7 mmHg. Among these patients, 72% had hypertension, 56.4% had diabetes, 28.9% had ischemic heart disease, and 25.4% had cerebrovascular disease. From 2012 to 2020, there was no change in the percentage of hypertension in each age group. The rate of grade II and III hypertension was predominantly male in the younger population (the twenties to fifties), but it shifted to females in the older population (over sixties). This gender disparity was more pronounced in the grade III hypertension group. Patients with cerebrovascular death had higher rates of hypertension (60.7 percent [gradeI; 26.2%, gradeII; 17.3%, gradeIII; 17.3%]) than those with heart failure death (32.9 percent [gradeI; 18.3%, gradeII; 8.4%, gradeIII; 6.2%]). Conclusion: Using the WADDA system, we summarized recent trends in BP of Japanese dialysis patients. We discovered that the rate of hypertension in patients undergoing dialysis has remained high (around 70%) and has not changed over the last decade. Furthermore, we discovered higher rates of hypertension, particularly in younger males, implying that optimal BP management for these populations may reduce cerebrovascular mortality.

Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients

ObjectivesThere is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined.MethodsBaseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients.ResultsThe maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL.ConclusionsThe presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

Toward Revision of the ‘Best Practice for Diabetic Patients on Hemodialysis 2012’

Diabetic nephropathy is the leading cause of dialysis therapy worldwide. The number of diabetes patients on dialysis in clinical settings has been increasing in Japan. In 2013, the Japanese Society for Dialysis Therapy (JSDT) published the “Best Practice for Diabetic Patients on Hemodialysis 2012”. While glycated hemoglobin (HbA1c) is used mainly as a glycemic control index for dialysis patients overseas, Japan is the first country in the world to use glycated albumin (GA) for assessment. According to a survey conducted by the JSDT in 2018, the number of facilities measuring only HbA1c has decreased compared with 2013, while the number of facilities measuring GA or both has significantly increased. Ten years have passed since the publication of the first edition of the guidelines, and several clinical studies regarding the GA value and mortality of dialysis patients have been reported. In addition, novel antidiabetic agents have appeared, and continuous glucose monitoring of dialysis patients has been adopted. On the other hand, Japanese dialysis patients are rapidly aging, and the proportion of patients with malnutrition is increasing. Therefore, there is great variation among diabetes patients on dialysis with respect to their backgrounds and characteristics. This review covers the indices and targets of glycemic control, the treatment of hyperglycemia, and diet recommendations for dialysis patients with diabetes.

Sex Differences in Cause-specific Mortality in Japanese Dialysis Patients.

Objective The survival advantage of females over males is lost in dialysis patients in many countries. Japanese female hemodialysis patients, however, have a survival advantage over their male counterparts. This study explored causes of death that contribute to sex differences in all-cause mortality in Japanese dialysis patients. Methods Data from the Japanese Society for Dialysis Therapy registry and National Vital Statistics from 2017 and 2018 were used. Standardized mortality ratios, male-to-female mortality rate ratios, and age-adjusted differences between sexes were calculated for all-cause, cardiovascular, and non-cardiovascular mortality, as well as cause-specific mortality, in dialysis patients and the general population. Results During the 2-year study period, 41,006 and 21,254 deaths occurred in 417,740 and 225,292 patient-years in male and female dialysis patients, respectively. The age-standardized all-cause mortality ratio was 1.21 (95% confidence interval, 1.20-1.23) for male patients compared to female patients. The male-to-female mortality rate ratio for cardiovascular disease was about 1.4 in younger age categories but closer to 1.0 in older age categories. Conversely, the ratio for non-cardiovascular disease was about 1.3 in older age categories but closer to 1.0 in younger age categories. Death from infectious disease, malignancy, and heart failure contributed to 38.4%, 22.7%, and 12.1%, respectively, of the male-to-female difference in all-cause mortality of dialysis patients. Conclusion Low cardiovascular mortality in younger age categories and low non-cardiovascular mortality in older age categories contributed to the survival advantage of female Japanese dialysis patients. Infectious disease was the greatest contributor to sex differences in all-cause mortality.

Impact of adherence to CKD-MBD guidelines on mortality among Japanese dialysis patients: an ecological study.

This study evaluated the association between prefecture-level achievement of chronic kidney disease-mineral and bone disorder (CKD-MBD) parameter targets and mortality in Japanese dialysis patients. We conducted an ecological study of all prefectures in Japan using data from the Japanese Society of Dialysis Therapy and National Vital Statistics between 2016 and 2017. We calculated adherence rates to recommend target ranges for CKD-MBD parameters, including phosphate, corrected calcium, and parathyroid hormone (PTH), and explored associations of these rates with prefecture-specific standardized mortality rates (SMRs) among the general population and among prevalent dialysis patients using bivariate association analysis and structural equation modeling. Prefecture-level adherence to the target phosphate range was significantly and negatively associated with prefecture-specific SMRs in men (standardized estimate (β) = -0.61, p < 0.001) and women (β = -0.41, p < 0.001). However, prefecture-level adherence to the target corrected calcium range was significantly and negatively associated with prefecture-specific SMRs only in men (β = -0.28, p = 0.01). Meanwhile, prefecture-level adherence to the target PTH range was significantly and positively associated with prefecture-specific SMRs in men (β = 0.23, p = 0.04). Prefecture-level SMRs of females in the general population had a significant impact on prefecture-level SMRs of female dialysis patients (β = 0.27, p = 0.03). The models explained 52% of variance in SMR for men and 33% for women. A higher prefecture-level achievement rate of the target phosphate range recommended by the Japanese CKD-MBD guidelines was associated with a lower prefecture-specific SMR in the Japanese dialysis population.

Increased Monocyte/Lymphocyte Ratio as Risk Marker for Cardiovascular Events and Infectious Disease Hospitalization in Dialysis Patients

Introduction: In dialysis patients, cardiovascular disease (CVD) and infectious disease contribute to poor clinical outcomes. We investigated if a higher monocyte/lymphocyte ratio (MLR) is associated with an increased risk of CVD events and infectious disease hospitalizations in incident dialysis patients. Methods: In an ongoing observational prospective cohort study, 132 Japanese dialysis patients (age 58.7 ± 11.7 years; 70% men) starting dialysis therapy were enrolled and followed up for a median of 48.7 months. Laboratory biomarkers, including white blood cell count and its differential count, were determined at baseline. Event-free time and relative risks (RRs) were calculated using the Kaplan-Meier curves and Cox models, respectively. Results: When divided into 2 groups according to median MLR (0.35 [range, 0.27–0.46]), the periods without CVD events were significantly shorter in the high MLR group than in the low MLR group (log-rank test = 5.60, p = 0.018). The RR of CVD events, after adjusting for age, sex, and diabetes, was 2.43 (1.22–4.84) in the high MLR group compared to the low MLR group. The periods without infections requiring hospitalization were also shorter (log-rank test = 4.16, p = 0.041). The RR of infections requiring hospitalization was 1.98 (1.02–3.83) after the same adjustments. The number of CVD events was higher in the high MLR group (18.6 events per 100 person-years at risk [pyr]) than the low MLR group (11.1 events per 100 pyr). The duration of infectious disease hospitalization was longer in the high MLR group (6.3 days per pyr) than in the low MLR group (2.8 days per pyr). Conclusion: A higher MLR is associated with increased risks of both CVD events and infectious disease hospitalization in dialysis patients.

One-year outcomes of the pivotal clinical trial of a balloon-expandable transcatheter aortic valve implantation in Japanese dialysis patients

BackgroundDialysis patients with aortic stenosis are generally considered as being at extreme or high surgical risk. Herein, the first clinical trial was conducted to investigate clinical safety and effectiveness of transcatheter aortic valve replacement (TAVR) using the balloon-expandable transcatheter aortic valve (SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) in Japanese dialysis patients. MethodsThe clinical trial is a single arm, prospective, open, non-randomized, Japanese multicenter study. The primary purpose of this trial is to evaluate the efficacy and safety of TAVR using SAPIEN 3 in 28 Japanese dialysis patients. ResultsMean age was 79.2 years and 67.9% were male (Mean STS score was 14.3%). Transfemoral and transapical approaches were performed in 25 (89.3%) and 3 patients (10.7%), respectively. All bioprostheses were successfully implanted. Median intensive care unit stay and hospital stay after TAVR were 1.4 days and 6.3 days, respectively. In-hospital mortality was 3.6% and freedom from all-cause mortality at 1 year was 89.3%. Disabling stroke and life-threatening bleeding at 1 year was 7.7% and 8.5%, respectively. There was no structural valve deterioration during follow-up. New York Heart Association functional status, six-minute walk test, and EuroQOL visual analogue scale score significantly improved through 1 year compared with baseline. ConclusionsTAVR using SAPIEN 3 is safe and effective for the treatment of Japanese dialysis patients with symptomatic severe aortic valve stenosis.

P1373ERYTHROPOETIN RESISTANCE IN PRE-DIALYSIS PERIOD AND ITS RELATION TO PROGNOSIS IN JAPANESE INCIDENT DIALYSIS PATIENTS

Abstract Background and Aims Erythropoiesis stimulating agents (ESA) are essential for better quality of life and longer life expectancy in end-stage kidney disease patients (ESKD). Resistance to ESA leads to worse prognosis in hemodialysis and peritoneal dialysis patients. Resistance to ESA exists in pre-dialysis period. We studied the clinical significance of pre-dialysis resistance to ESA by investigating the erythropoietin resistance index (ERI) in patients with ESKD prior to dialysis induction and its association with mortality and cause of death in three-year follow-up after dialysis initiation. Method Subjects included 1,420 patients in 17 centers participating in Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from Oct. 2011 to Sep. 2013. ESA responsiveness was estimated by using erythropoietin resistance index (ERI) (U/kg/week/g/dL), which was calculated as weekly weight-adjusted epoetin dose divided by the hemoglobin (Hb) concentration before starting dialysis. We excluded 302 patients because ERI was not available. Thus, 1,118 subjects were enrolled. Subjects were divided into four categories of ERI; ERI &amp;lt; 5, 5≤ ERI &amp;lt;10, 10≤ ERI &amp;lt;15 and 15≤ ERI. Cumulative survival rates from all-cause, cardiovascular disease (CVD), infection and malignancy were compared by Kaplan-Meier method according to ERI categories. Three-year mortality was analyzed by logistic regression analysis adjusted by age, gender, Charlson comorbidity index (CCI), and ERI categories. Results During three-year follow-up period, 191 (17.1%) patients died. Age and female gender share were higher in proportion to ERI. Diabetes, coronary artery disease (CAD), and values of albumin (Alb) and brain natriuretic peptide (BNP) were not correlated with ERI (Table 1). Kaplan-Meier survival curve showed that patients with the highest ERI (15≤ ERI) had a higher all-cause mortality (Log rank test p=0.002, Figure 1). Concerning the cause of death, mortality from infection (p=0.023, Figure 2) and malignancy (p=0.031) were high in the highest ERI category, however there was no significant difference in each ERI category regarding CVD mortality (p=0.33). According to multivariate analysis analyses by logistic regression model, all-cause (odd ratio [OD]: 1.65, 95% confidence interval [CI]: 1.14-2.38, p=0.008) and infection-related mortality (OR: 2.13, 95% CI: 1.08-4.11, p=0.029) were significantly correlated with the highest ERI category, but unexpectedly CVD mortality was not (OR: 1.04, 95% CI: 0.59-1.75, p=0.90). Mortality from malignancy did not reach the significant level (OR: 1.92, 95% CI: 0.96-3.73, p=0.063) and may require longer observation period for analysis. Conclusion Pre-dialysis ERI is a prognostic marker in Japanese dialysis patients and predicts the susceptibility to infection.

Inter-leg systolic blood pressure difference predicts cardiovascular events and mortality in incident hemodialysis patients.

High inter-arm blood pressure difference, a marker of vascular disease, may be difficult to assess in hemodialysis patients with arm arteriovenous fistulae. We investigated if high inter-leg systolic blood pressure difference associates with cardiovascular events and increased mortality in hemodialysis patients. Among 118 incident Japanese dialysis patients, bilateral leg blood pressure, arm blood pressure, brachial-ankle pulse wave velocity, and ankle-brachial index were measured, and the relative risk associated with inter-leg systolic blood pressure difference and other indices of vascular status was analyzed. During follow-up (median, 46 months), 18 deaths and 75 cardiovascular events occurred in 38 patients. Kaplan-Meier curves showed that higher inter-leg systolic blood pressure difference was associated with overall (log-rank 9.35, p = 0.002) and cardiovascular (log-rank 5.81, p = 0.02) mortality. The period from the start of dialysis therapy to the first cardiovascular event was shorter as inter-leg systolic blood pressure difference increased (log-rank 23.7, p < 0.0001). In Cox hazard models, inter-leg systolic blood pressure difference greater than median independently predicted deaths (relative risk, 3.8; 95% confidence interval, 1.3-13.9) and cardiovascular events (relative risk, 3.9; 95% confidence interval, 1.9-9.21) after adjustments for age, sex, nutritional status, and diabetes, whereas other indices were not related to the risks. For well-nourished, moderately malnourished, and severely malnourished patients, the cumulative number of cardiovascular events in the high-inter-leg systolic blood pressure difference patients were 4.96, 31.44, and 55.18 events per 100 patient-years. Higher inter-leg systolic blood pressure difference associated with increased risk of mortality and cardiovascular events suggesting that wider application of inter-leg systolic blood pressure difference measurements may be warranted in hemodialysis patients.

Legal policy challenges in withdrawal of dialysis treatment in Japan

Abstract Issue/problem In 2017, Japanese dialysis patients and kidney transplant cases numbered roughly 330,000 and 1,700, respectively. In March 2019, a patient died after a physician terminated her kidney dialysis at a hospital in Tokyo. The Tokyo Metropolitan Government and the Japanese Society for Dialysis Therapy (JSDT) investigated the case, questioning the patient’s terminal status and desire to withdraw her request to terminate dialysis. Description of the problem No Japanese law addresses treatment withdrawal, but several court decisions and the Ministry of Health, Labor and Welfare’s process guidelines and JSDT guidelines address treatment withdrawal from terminal patients. We examined relevant court decisions and guidelines, identifying three legal policy issues that may impact legal policy discussions on treatment withdrawal in other countries, regardless of the enactment status of such laws. Results First, the patient was not “terminally ill” as defined by the court rulings and guidelines. Second, a clear decision based on appropriate informed consent from the patient seemed absent, violating the court rulings and guidelines. Third, the physician’s judgment of patient competency for decision-making may have been missing. Lessons We considered problems beyond the court rulings and guidelines by focusing on the patient’s right to self-determination and treatment refusal in other countries. The Patient Self-Determination Act and the Patient’s Bill of Rights (US) as well as court rulings and the NHS Charter (UK) guarantee such rights, and collectively enable competent patients in the US, UK, and elsewhere to refuse dialysis even if they are not terminal. Japanese legislation does not guarantee such patient rights or the explicit allowance/prohibition of treatment withdrawal, regardless of the patient’s terminal status; enactment of such laws should be considered. Key messages We identified legal ambiguity due to a lack of the patient’s right to both self-determination and treatment refusal. This could impact the international discussion on dialysis treatment withdrawal.

Outcomes of cardiovascular surgery for chronic dialysis patients in current Japan.

Background The number of dialysis patients in Japan is rising, with an increasing number requiring cardiovascular surgery. Methods We investigated the short- and long-term outcomes in 70 dialysis patients among a total of 1124 who underwent cardiovascular surgery in our hospital between 2004 and 2016. We investigated outcomes following open surgery and identified factors that affected the prognosis. We also compared the long-term survival rate with the survival rate of the Japanese dialysis population. Results The long-term survival rate was 70.6%, 51.1%, and 19.2% after 3, 5, and 10 years, respectively. The causes of long-term death were heart disease in 8 patients, cerebrovascular disease in 7, cachexia in 3, infection in 2, and other causes in 3. The freedom from cardiac death was 88.7%, 77.9%, and 54.9% after 3, 5, and 10 years, respectively. Multivariate analysis using Cox’s proportional hazard model showed that a history of atherosclerosis obliterans (hazard ratio 5.4, p = 0.05) and mediastinitis (hazard ratio 10.2, p = 0.03) were risk factors for death in long-term follow-up, and a history of atherosclerosis obliterans was an independent risk factor for cardiac death in long-term follow-up (hazard ratio 5.3, p = 0.01). Five-year survival of the study subjects was comparable to that of the Japanese dialysis population. Conclusions The prognosis for dialysis patients after open surgery was equivalent to that of Japanese dialysis patients in general. A high proportion of late postoperative deaths were due to heart disease. Patients with atherosclerosis obliterans had a poor prognosis.

Current status of vascular access in Japan-from Dialysis Access Symposium 2017.

At the second Dialysis Access Symposium held in Nagoya, Japan, a proposal was made to investigate the differences in vascular access methods used in different countries. In this article, we describe the management of vascular access in Japan. The Japanese population is rapidly aging, and the proportion of elderly patients on dialysis is also increasing. There were 325,000 dialysis patients in Japan at the end of 2015, of whom 65.1% were aged 65 years or above. The number of patients with diabetic nephropathy or nephrosclerosis as the underlying condition is also increasing, whereas the number with chronic glomerulonephritis is steadily decreasing. The Japanese health insurance system enables patients to undergo medical treatment at almost no out-of-pocket cost. Percutaneous transluminal angioplasty suffers from a severe device lag compared with other countries, but although there are limitations on permitted devices, the use of those that have been authorized is covered by medical insurance. One important point that is unique to Japan is that vascular access is performed and managed by doctors involved in dialysis across a wide range of disciplines, including nephrologists, surgeons, and urologists. This may be one factor contributing to the good survival prognosis of Japanese dialysis patients.

Abstract P307: Additional Prognostic Value of Toe-Brachial Index Beyond Ankle-Brachial Index in Hemodialysis Patients

Background: Although ankle-brachial index (ABI) is considered the first-line diagnostic test for peripheral artery disease (PAD), ABI can be falsely elevated in some patients with uncompressible ankle arteries. In those patients, toe-brachial index (TBI) is recommended as an alternative test. However, whether TBI provides additional prognostic information beyond ABI is unknown. Methods: We examined data from 247 Japanese dialysis patients (mean age 66 years). ABI and TBI were measured bilaterally on the same day, and the lower values were used for analysis. We explored quartiles of ABI and TBI as well as three categories of low ABI (≤0.9), normal/high ABI (&gt;0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (&gt;0.6) (very few with low ABI and normal TBI). Multivariable Cox models were used to quantify the associations of ABI and TBI with all-cause mortality. Results: During a mean follow-up of 5.2 years, we observed 116 deaths. As anticipated, ABI showed a J-shaped association with mortality, with the higher risk seen in the lowest quartile (adjusted hazard ratio 2.70 [95% CI 1.38-5.30]) and the highest quartile (1.46 [0.73-2.90]) vs. the second highest quartile. In contrast, lower TBI showed a dose-response association with mortality (e.g., adjusted hazard ratios 2.41 [1.16-5.01] and 2.21 [1.04-4.71] in the lowest two quartiles vs. the highest quartile). When three categories by ABI and TBI were analyzed, low ABI showed worst prognosis, followed by normal/high ABI + low TBI and then normal/high ABI + normal TBI (Figure). Higher mortality risk in normal/high ABI + low TBI vs. normal/high ABI + normal TBI remained significant after accounting for potential confounders (adjusted hazard ratio 1.84 [1.04-3.25]). Conclusions: Lower TBI was independently associated with higher mortality risk in patients on dialysis and classified risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in dialysis patients.