Japanese Hemodialysis Patients Research Articles

Development of a prognostic risk score to predict early mortality in incident elderly Japanese hemodialysis patients.

Information of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients. We analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study. Using the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (<20), yes = 2, no = 0; cancer, yes = 1, no = 0; dementia, yes = 3, no = 0; lower creatinine (<6.5 mg/dL), yes = 1, no = 0; lower albumin (<3.0 g/dL), yes = 3, no = 0; normal or high calcium (≥8.5 mg/dL), yes = 1, no = 0; and higher C reactive protein (>2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (p<0.001). We developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.

Anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine and associated factors in Japanese hemodialysis patients.

We assessed the anti-SARS-CoV-2 spike antibody response to the third dose of BNT162b2 mRNA COVID-19 vaccine in Japanese hemodialysis patients and determined factors associated with the anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine. Overall, 64 patients (37 males, 27 females; mean age 71.4 ± 11.7 years) were enrolled in this single-center, prospective, longitudinal study. Anti-SARS-CoV-2 spike antibody titers were compared between hemodialysis patients and 18 healthcare workers (8 males, 10 females; mean age 45.9 ± 12.2 years). Multiple linear regression analysis was used to identify factors associated with the anti-SARS-CoV-2 spike antibody titer after the third vaccination. There was no significant difference in anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination between hemodialysis patients and healthcare workers (18,500 [interquartile range, 11,000-34,500] vs. 11,500 [interquartile range, 7,918-19,500], all values in AU/mL; p = 0.17). Uric acid (standard coefficient [β] = -0.203, p = 0.02), transferrin saturation (β = -0.269, p = 0.003), and log-anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (β = 0.440, p < 0.001) correlated with the log-anti-SARS-CoV-2 spike antibody titer 4 weeks after the third vaccination. In contrast, only the log-anti-SARS-CoV-2 spike antibody titer 1 week before the third vaccination (β = 0.410, p < 0.001) correlated with the log-anti-SARS-CoV-2 spike antibody titer 12 weeks after the third vaccination. The anti-SARS-CoV-2 spike antibody titer after the third dose of COVID-19 vaccine was comparable between hemodialysis patients and healthcare workers. Uric acid concentration, transferrin saturation, and anti-SARS-CoV-2 spike antibody titer before the third dose were associated with the anti-SARS-CoV-2 spike antibody titer after the third dose in Japanese hemodialysis patients.

2429. Epidemiology and Risk Factors for Vascular Access-associated Infections in Japanese Hemodialysis Patients

Abstract Background Surveillance of vascular access-associated infections (VAIs) in patients on hemodialysis has been well established in the United States, but not so in other countries including Japan. Our group established a voluntary VAI surveillance scheme, Dialysis Surveillance Network Japan (DSNJ), which is in operation for over 10 years. The purpose of this study is to describe the epidemiology and identify risk factors for VAI in patients on hemodialysis in Japan. Methods Data collected through DSNJ from January 2008 to December 2021 were used. Incidence of VAI was calculated by the number of infection per 1,000 dialysis sessions. Potential risk factors analyzed in this study included type of access, diabetes, indication of catheter use and seasonality Results During the study period, 4,919,834 dialysis sessions were surveyed at 52 hospitals and 1,146 VAI were observed, with an overall incidence of 0.23 per 1,000 sessions. The incidence declined over time. The incidences by the type of access were 0.05 (203 VAI in 4,285,758 dialysis sessions) for arteriovenous fistula (AVF), 0.11 (17/157,754) for superficialization of brachial artery (SBA), 0.53 (127/240,289) for arteriovenous graft (AVG), 1.33 (219/164,195) for cuffed catheter (CC) and 8.07 (580/71,838) for non-cuffed catheter (NCC). NCC had significantly higher risk for VAI than any other type of access. The most frequently accountable pathogen was methicillin-susceptible Staphylococcus aureus. The risk of diabetes for VAI was not significant in patients with either NCC or CC (NCC: RR 1.18, 95%CI: 0.98-1.43, CC: RR0.86, 95%CI: 0.64-1.16). NCC inserted at the femoral site had significantly higher risk of VAI compared to that at internal jugular site (RR 1.47, 95%CI: 1.21-1.78). This was also true for CC (RR:2.41, 95%CI: 1.34-4.34). NCC used at the induction of hemodialysis was more likely to be complicated with VAI than NCC used as a temporary substitute (RR 1.50, 95%CI: 1.22-1.84). Fifty-five percent (634/1,146) of VAI occurred in summer (May to October), indicating a seasonal variation in the incidence of VAI. Conclusion Our surveillance scheme revealed epidemiology and risk factors for VAI in Japanese hemodialysis patients. These findings might lead to better control VAIs in patients on hemodialysis. Disclosures All Authors: No reported disclosures

Impact of nutrition and inflammation indicators on peritoneal dialysis initiation and management.

The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation. A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. The median age and follow-up period were 65years and 54months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively). Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD.

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.

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study.

Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT). A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52weeks; the starting dose was 50μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60-240pg/mL (target achievement rate) at week 18. A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5mg/dL recovered to ≥7.5mg/dL immediately after the interruption. In haemodialysis patients with SHPT, upacicalcet doses of 25-300μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.

Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia

Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels. Therefore, drugs with novel mechanisms of action that can be added to existing PBs to further lower serum phosphorus levels are desired. Tenapanor, a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporters, decreases passive phosphate absorption in the intestine, thereby decreasing serum phosphorus levels. This study evaluated the efficacy and safety of tenapanor treatment with up-titration when added to PBs among Japanese hemodialysis patients with hyperphosphatemia poorly controlled by PBs alone. In total, 169 patients taking PBs whose serum phosphorus level was≥6.1 and<10.0 mg/dl initiated the 8-week treatment (placebo+ PB, n= 85; tenapanor+ PB, n= 84). The least squares mean change from baseline to week 8 in serum phosphorus level was-0.24 and-2.00 mg/dl in the placebo and tenapanor groups, respectively, with a statistically significant difference between groups (-1.76 mg/dl; P< 0.0001). Diarrhea as a treatment-emergent adverse event (TEAE) occurred in 14.1% and 63.1% of patients in the placebo and tenapanor groups, respectively. All diarrhea events were mild or moderate. Tenapanor added to PBs improved serum phosphorus levels that could not previously be controlled by PBs alone, and no new safety concerns were raised.

Robust antibody response after the third mRNA coronavirus vaccination in Japanese hemodialysis patients

BackgroundHemodialysis patients have chronic kidney disease, are often elderly, and have many complications such as hypertension, type 2 diabetes, cardiac disease, and cerebrovascular disease. Therefore, hemodialysis patients infected with COVID-19 are prone to severe disease. Vaccination is the most promising means of preventing the onset and reducing the severity of COVID-19. However, many reports have found that anti-spike antibody titers after two doses of mRNA vaccine are lower in hemodialysis patients than in healthy controls. For this reason, a third vaccination is recommended for hemodialysis patients. In Japan, there are several reports of a third vaccination, especially for hemodialysis patients. In this study, we also examined the antibody response to COVID-19 vaccine in Japanese hemodialysis patients who received the third dose of the vaccine.MethodsStudy participants received a third vaccination (257 with BNT162b2 vaccine and 5 with mRNA-1273 vaccine) approximately 7–9 months after the second (BNT162b2 vaccine). Anti-SARS-CoV-2 spike IgG antibody titers were measured (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 healthcare workers approximately 2 weeks after the second vaccination and in 162 hemodialysis patients and 100 healthcare workers approximately 2 weeks after the third.ResultsFollowing the second vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 2728.7 AU/mL (IQR, 1024.2–7688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9346.1–2,4500 AU/mL) in the controls. Following the third vaccination, 99.4% of the hemodialysis group (only one person tested negative for the antibody) and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 20,000 AU/mL (IQR, 7729–37,000 AU/mL) in the hemodialysis group and 21,500 AU/ml (IQR, 14,000–32,250 AU/mL) in the control group. The factors involved in the low response to the BNT152b2 vaccine after the second vaccination included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders. However, in hemodialysis patients, the response after the third vaccination was excellent, and all factors associated with the suppressed response to these vaccines were no longer significant.ConclusionsThe humoral response of hemodialysis patients to two doses of mRNA vaccine was weaker than that of healthy controls. However, a third vaccination eliminated that difference.

#5269 THE NUTRITIONAL ASSESSMENT TOOLS TO IDENTIFY PATIENTS AT INCREASED SARCOPENIA RISK

Abstract Background and Aims Protein-energy wasting (PEW), debilitating nutritional and metabolic disorder marked by a systemic reduction in protein and energy store, is prevalent among patients with end stage renal disease (ESRD). The magnitude of malnutrition among patients undergoing hemodialysis has been positively associated with, the risk of all-cause mortality, particularly due to cardiovascular disease and infections. Additionally, inadequate nutritional status has been implicated in the development of sarcopenia, characterized by decreased muscle mass, weakened muscle strength, and impaired physical function. As such, routine management of nutritional status may be crucial aspect of care for these patients. In addition to the nutritional risk index for Japanese hemodialysis patients (NRI-JH), developed for the diagnosis of PEW, the geriatric nutritional risk index (GNRI) and mini nutritional assessment short-form (MNA-SF) are frequently utilized as nutritional indices in patients on hemodialysis. However, few studies have compared the magnitude of associations between these nutritional measure and sarcopenia in patients undergoing hemodialysis. This study aimed to evaluate the degree of association between nutritional assessments and sarcopenia in this patient population. Method The current cross-sectional study recruited outpatients receiving maintenance hemodialysis between June 2019 and December 2021. The study collected patient information, including age, gender, body mass index, dialysis duration, primary kidney diseases, 11 comorbid conditions, and laboratory parameters (such as serum albumin, serum creatinine, and total cholesterol), from medical records. Physical therapists assessed muscle mass (skeletal muscle index [SMI]), muscle strength (handgrip strength), and physical performance (short physical performance battery [SPPB]), and sarcopenia was diagnosed when patients presented with low muscle mass (SMI &amp;lt;7.0 kg/m2 for males, &amp;lt;5.7 kg/m2 for females) and low muscle strength (handgrip strength &amp;lt;28.0kg for males, &amp;lt;18 kg for females) or low physical performance (SPPB ≤9) based on the Asian Working Group for Sarcopenia 2019 criteria. The study employed the NRI-JH, GNRI, and MNA-SF as markers of nutritional status. The NRI-JH was calculated based on body mass index, serum albumin, serum creatinine, and total cholesterol. Logistic regression analysis was performed to examine the associations of NRI-JH, GNRI, and MNA-SF with sarcopenia among patients on hemodialysis. Results Sixty-five patients undergoing hemodialysis were analyzed in this study. The mean age of the patients was 78.3 ± 10.7 years, with 36.9% being female. The average duration of dialysis was 6.4 ± 3.9 years. The most frequently observed underlying kidney disease was diabetes mellitus, followed by hypertension. The prevalence of sarcopenia was found to be 60.0%. After adjustment for the effects of age, gender, dialysis duration, and comorbidity index, patients with a lower score on the NRI-JH were significantly more prone to sarcopenia (odds ratio per 1-point increase, 1.33; 95% confidence interval, 1.04–1.69). The NRI-JH was demonstrated to have a stronger association with sarcopenia compared to the others (Table 1). Conclusion The NRI-JH and GNRI were significantly associated with risk of sarcopenia. The NRI-JH demonstrated a stronger association with the risk of sarcopenia compared to the GNRI.

Malnutrition and Insulin Resistance May Interact with Metabolic Syndrome in Prevalent Hemodialysis Patients

We sought to determine the prevalence of metabolic syndrome (Mets) and whether 100 cm2 of visceral fatty area (VFA) measured by computed tomography (CT) validates the criteria of waist circumference (WC) in hemodialysis (HD) patients. The study comprised 141 HD patients. Mets was defined according to the criteria of Adult Treatment Panel III (ATP III) and the modified criteria of National Cholesterol Education Program (NCEP) that defines abdominal obesity as a WC of >=85 cm in men and >=90 cm in women. The prevalence of Mets was 31.9% in men and 13.6% in women. However, the prevalence of patients with a body mass index over 25 in all HD patients was only 11.2%. The visceral fatty area (VFA) measured by CT showed a strong positive correlation with WC. The patients with Mets, comparing with those without Mets, have significantly shorter duration of HD, higher high-sensitive C-reactive protein, and higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). In the patients with Mets, there was a significant negative correlation between HOMA-IR and serum albumin levels. Multivariate logistic regression analysis showed that HOMA-IR and short duration of HD were chosen as independent risk factors for Mets. Mets is more prevalent in HD patients. In Japanese HD patients, 100 cm2 of VFA corresponded to a WC of 85 cm in men and 90 cm in women, thus confirming the validity of the modified criteria. HOMA-IR and serum albumin were significantly correlated in HD patients with Mets.

Association of Hyperkalemia and Hypokalemia with Patient Characteristics and Clinical Outcomes in Japanese Hemodialysis (HD) Patients.

This study aimed to examine the characteristics and clinical outcomes of Japanese hemodialysis patients with dyskalemia. A retrospective study was conducted using a large Japanese hospital group database. Outpatients undergoing thrice-a-week maintenance hemodialysis were stratified into hyperkalemia, hypokalemia, and normokalemia groups based on their pre-dialysis serum potassium (sK) levels during the three-month baseline period. Baseline characteristics of the three groups were described and compared for the following outcomes during follow-up: all-cause mortality, all-cause hospitalization, major adverse cardiovascular events (MACE), cardiac arrest, fatal arrythmia, and death related to arrhythmia. The study included 2846 eligible patients, of which 67% were men with a mean age of 65.65 (SD: 12.63) years. When compared with the normokalemia group (n = 1624, 57.06%), patients in the hypokalemia group (n = 313, 11.00%) were older and suffered from malnutrition, whereas patients in the hyperkalemia group (n = 909, 31.94%) had longer dialysis vintage. The hazard ratios for all-cause mortality and MACE in the hypokalemia group were 1.47 (95% confidence interval [CI], 1.13-1.92) and 1.48 (95% CI, 1.17-1.86), respectively, whereas that of death related to arrhythmia in the hyperkalemia group was 3.11 (95% CI, 1.03-9.33). Thus, dyskalemia in maintenance hemodialysis patients was associated with adverse outcomes, suggesting the importance of optimized sK levels.

Humoral response after BNT162b2 vaccine in Japanese hemodialysis patients

BackgroundHemodialysis patients are more likely to be severely affected if infected by COVID-19. Contributing factors include chronic kidney disease, old age, hypertension, type 2 diabetes, heart disease, and cerebrovascular disease. Therefore, action against COVID-19 for hemodialysis patients is an urgent issue. Vaccines are effective in preventing COVID 19 infection. In hemodialysis patients, however, responses to hepatitis B and influenza vaccines are reportedly weak. The BNT162b2 vaccine has shown an efficacy rate of about 95% in the general population, but as far as we know there are only several reports of efficacy data in hemodialysis patients in Japan.MethodsWe assessed serum anti-SARS-CoV-2 IgG antibody (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 health care workers. The exclusion criterion was positivity for SARS-CoV-2 IgG antibody before vaccination. Adverse reactions to BNT162b2 vaccine were evaluated through interviews.ResultsFollowing vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of anti-spike antibody was 2,728.7 AU/mL (IQR, 1,024.2–7,688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9,346.1–2,4500 AU/mL) in the health care workers group. The factors involved in the low response to the BNT152b2 vaccine included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders.ConclusionsHumoral responses to BNT162b2 vaccine in hemodialysis patients are weaker than in a healthy control sample. Booster vaccination is necessary for hemodialysis patients, especially those showing a weak or non-response to the two-dose BNT162b2 vaccine.Trial registration UMIN, UMIN000047032. Registered 28 February 2022, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_reg_rec.cgi.

PS-C18-8: MEAN ANNUAL INTRADIALYTIC BLOOD PRESSURE DECLINE AND CARDIOVASCULAR EVENTS IN JAPANESE MAINTENANCE HEMODIALYSIS PATIENTS

Objective: A decline in the intradialytic systolic blood pressure (SBP), which defines intradialytic hypotension, is associated with a greater risk of intradialytic symptoms. Intradialytic SBP decline may be associated with higher all-cause mortality. However, this association has neither been studied in Japanese hemodialysis (HD) patients, nor has seasonal variations in intradialytic SBP decline been considered. We evaluated the association between the mean annual intradialytic SBP decline in Japanese HD patients and clinical outcomes, including major adverse cardiovascular events (MACEs). Design and method: This retrospective cohort study included 47,219 HD sessions in 307 patients undergoing HD over one year (April 2019 to March 2020) in three dialysis clinics. The mean annual intradialytic SBP decline (predialysis SBP-nadir intradialytic SBP) for each patient was determined. The association of the mean annual intradialytic SBP decline with clinical outcomes, including MACEs, was assessed from April 2020 until March 2022. MACEs included cardiovascular death, nonfatal myocardial infarction or unstable angina, stroke, heart failure, and other severe cardiovascular events requiring hospitalization. Results: The study participants included 202 males (66%). The mean patient age was 69.0 ± 12.4 years and the median duration of HD was 4.1 (2.0–7.7) years. The mean annual intradialytic SBP decline was 28.2 ± 14.8 mmHg. MACEs occurred in 77 cases (25%), death or hospitalization due to a decline in Activities of Daily Living (death or hospitalization) occurred in 56 (18%) cases, and all-cause hospitalization occurred in 184 cases (60%). A Cox regression analysis adjusted for age, sex, HD duration, Charlson comorbidity index, and the mean annual predialysis SBP and ultrafiltration rate, showed that a greater intradialytic SBP decline (per 10) was significantly associated with increased risk of MACEs (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.09–1.54). Moreover, the greater intradialytic SBP decline (per 10) was associated with increased risks of death or hospitalization (HR, 1.32; 95% CI, 1.08–1.62) and all-cause hospitalization (HR, 1.22; 95% CI, 1.07–1.39). Conclusions: In Japanese maintenance HD patients, a greater intradialytic SBP decline was associated with worse clinical outcomes, including increased risks of MACEs, death or hospitalization, and all-cause hospitalization. Further studies are warranted to investigate interventions to attenuate intradialytic SBP decline and improve the prognosis of Japanese HD patients.

Multifaceted Nutritional Disorders in Elderly Patients Undergoing Dialysis

Advances in medicine have resulted in increased longevity, which has consequently led to unexpected geriatric syndromes, such as frailty and sarcopenia. Patients with end-stage kidney disease, especially those receiving dialysis treatment, often show characteristic reductions in body protein and energy storage, termed protein energy wasting (PEW). Therefore, maintenance of nutritional condition has a key role in defending against both geriatric syndromes and PEW, which share several components in elderly individuals undergoing hemodialysis. To counteract the development of an undesirable condition, nutritional evaluation is indispensable. In addition to simple measurements of body mass index, and serum albumin and creatinine, a composite nutritional assessment including a malnutrition inflammation score is useful, although subjective elements are included and a well-trained examiner is required. On the other hand, the geriatric nutritional risk index and nutritional risk index for Japanese hemodialysis patients (NRI-JH) are objective tools, and easy to use in clinical settings. Undernutrition is closely related to infectious events and the results of an infection are often serious in elderly patients, even those with survival, with large medical costs incurred. Together with appropriate nutritional evaluation, it is necessary to clarify the underlying relationship of PEW with infection for improvement of prognosis in affected elderly individuals.

Cardiovascular events by different target hemoglobin levels in ESA-hyporesponsive hemodialysis patients: a multicenter, open-label, randomized controlled study

BackgroundThe incidence of cardiovascular (CV) events is high in hemodialysis (HD) patients and is associated with hyporesponsiveness to erythropoiesis-stimulating agents (ESAs). However, there are no recommended target hemoglobin ranges for ESA-hyporesponsive patients.MethodsWe randomly assigned 304 ESA-treated HD patients with ESA hyporesponsiveness to a proactive treatment group (target hemoglobin level 11 g/dL) or maintenance treatment group (target hemoglobin level 9–10 g/dL), both of which received epoetin beta pegol. The primary outcome was time to the first CV event. CV events included cardiac death, heart failure, and acute coronary syndrome requiring hospitalization. The patients were followed for 24 months.ResultsThe proactive and maintenance treatment groups had mean baseline hemoglobin levels of 9.34 and 9.32 g/dL, respectively. Mean hemoglobin levels during the observation period were 10.58 and 10.26 g/dL (P < 0.001), and mean durations of hemoglobin level > 10.5 g/dL were 11.5 and 8.6 months (P < 0.001), respectively. Cox proportional hazards analysis demonstrated a significantly lower risk of CV events in the proactive group (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19–0.96). This lower risk was driven by lower incidence of hospitalization-required congestive heart failure. A longer duration of hemoglobin level > 10.5 g/dL was associated with a lower risk of CV events (HR, 0.92/month; 95% CI, 0.87–0.98).ConclusionsTargeting hemoglobin levels of 11 g/dL with epoetin beta pegol reduces CV risk in Japanese HD patients with ESA hyporesponsiveness.Trial registration: University Hospital Medical Information Network (UMIN) database (UMIN000010138), registered on March 1, 2013.

Intradialytic parenteral nutrition using a standard amino acid solution not for renal failure in maintenance hemodialysis patients with malnutrition: a multicenter pilot study

BackgroundStandard amino acid solutions have recently been removed from the contraindications for use in dialysis patients in Japan. However, the details of their safety and efficacy in these patients are still not known. In this study, we investigated the safety and efficacy of intradialytic parenteral nutrition (IDPN) using ENEFLUID® injection containing standard amino acids, glucose, electrolytes, fats, and water-soluble vitamins in maintenance hemodialysis patients with malnutrition.MethodsThis clinical trial was designed as a multicenter, prospective, non-randomized, open-label, single-arm, observational pilot study. The participants were patients on maintenance hemodialysis who were in the nutritional high-risk group according to the Nutritional Risk Index for Japanese Hemodialysis Patients. One bag of ENEFLUID® injection was administered during every hemodialysis session for 12 weeks. The primary endpoint was change in serum transthyretin levels between before and after the 12-week period. As safety endpoints, we evaluated changes in body fluid volume and blood biochemical tests, including blood urea nitrogen and electrolytes, as well as blood glucose variability using flash glucose monitoring (FGM).ResultsThe mean age and body mass index of the 13 participants were 79.0 ± 10.7 years and 18.0 ± 1.7 kg/m2, respectively. No significant changes were observed in nutritional parameters, including serum transthyretin, between before and after the start of the study. After IDPN initiation, there was no obvious fluid overload or significant changes in blood biochemical tests, including electrolytes, and the treatment could be safely continued for 12 weeks. In the FGM analysis, asymptomatic hypoglycemia during hemodialysis was observed at the beginning of the study, but there was a trend toward improvement after 12 weeks (area over the curve < 70 mg/dl per dialysis session: 747.5 ± 1333.9 to 21.6 ± 54.3, P = 0.09).ConclusionsIDPN using ENEFLUID® injection can be safely continued, although it does not significantly improve markers of nutritional status. It also showed the potential to ameliorate asymptomatic hypoglycemia during hemodialysis sessions. More detailed studies of the improvement in nutritional indicators are needed.Trial registration: This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on May 9, 2021 (registration ID, UMIN000044051).

An investigation into possible sex differences in Association of Haemoglobin with survival among Haemodialysis patients in the J-DOPPS cohort.

Lower haemoglobin levels are common among females without kidney diseases. However, little is known about the sex-specific management of anaemia in haemodialysis patients. This prospective cohort study investigated the role of sex differences in the association between categorical baseline or time-varying haemoglobin levels and all-cause mortality via cox regression using data from 6890 patients in the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS, 2005-2015). Likelihood ratio tests were used to evaluate the effect modification of sex on the relationship between haemoglobin and mortality. A total of 781 patients died during the median follow-up of 31 months. Mortality risk, adjusted for case mix, varied between five haemoglobin categories, with the highest category (≥12 g/dL) having a hazard ratio of 0.73 (0.41-1.29) for females and 2.02 (1.03-3.95) for males versus 10-10.9g/dL. Despite this difference, the p-value comparing the overall among males versus females was.35. Similar associations were observed in models stratified by patient age (<75 years), time on dialysis (≤1year), and models lagging the haemoglobin exposure. The results based on this sample of Japanese haemodialysis patients did not support the hypothesis that the association between haemoglobin and survival differed by sex. We also could not conclude that the association was identical, as the parameter estimates are consistent with male patients having a relatively greater mortality risk than female patients at higher haemoglobin levels. More detailed investigations into the effects of higher haemoglobin levels by sex might help better understand strategies for anaemia management.

MO519: Ferric Citrate Hydrate Improves Levels of Transferrin Saturation in Hemodialysis Patients With Lower Levels of Transferrin Saturation

Abstract BACKGROUND AND AIMS Iron deficiency identified by transferrin saturation (TSAT) is reported as a risk factor for all-cause mortality and cardiovascular events in non-dialysis dependent (NDD) chronic kidney disease (CKD) [1, 2] and for all-cause mortality in hemodialysis patients [3]. Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in CKD patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan in 2021. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with NDD-CKD. FC or ferric citrate increased TSAT in patients with NDD-CKD and IDA [4]. However, a few data show that whether FC or ferric citrate has the similar effect in hemodialysis patients whose TSAT is &amp;lt;20%. Considering the additional indication of IDA in Japan, we investigated the FC's effect on TSAT by using the data obtained from the ASTRIO study [5], which was conducted in Japanese hemodialysis (HD) patients. METHOD We conducted a retrospective study using the data of ASTRIO study [5], which is a randomized, prospective, open-label, multicenter 24-week study to investigate the FC's effect on anemia management compared with non-iron-based phosphate binders (PBs) in Japanese HD patients with hyperphosphatemia. Ninety-three patients taking non-iron-based PBs were randomized 1:1 to continue PBs (control) or switch to FC. During 24-week study, serum phosphate and hemoglobin were controlled, 3.5–6.0 mg/dL and 10–12 g/dL, respectively. From 93 patients (FC, n = 48; control, n = 45), we extracted 41 patients (FC, n = 21; control, n = 20) whose TSAT at baseline was &amp;lt;20% and compared the levels of TSAT and other iron related parameters between FC group and control group. RESULTS In the ASTRIO study, the mean (SD) levels of TSAT (%) was 14.3 (4.0) at baseline and rapidly increased to 25.0 (11.1) at 4 weeks in the FC group. After that, the levels of TSAT were almost unchanged in the FC group, whereas, in the control group, the mean (SD) levels of TSAT were almost unchanged during the 24-week study. The mean (SD) levels of serum ferritin gradually increased until week 12 and subsequently showed to be stabilized in the FC group, whereas, in the control group, these were almost unchanged during the 24-week study (Table 1). CONCLUSION In Japanese HD patients whose TSAT was &amp;lt;20%, FC rapidly increased TSAT compared with control. We will also investigate the FC's effect on TSAT in HD patients from the post-marketing surveillance study, the prospective, multicenter and observational, up to maximum 2 years treatment.

Selenium Associates With Response to Erythropoiesis-Stimulating Agents in Hemodialysis Patients

IntroductionImpaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients.MethodsIn this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index.ResultsOf the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (β = −0.11, P < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 μg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables.ConclusionSerum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.