Erythropoiesis-stimulating agent hyporesponsiveness was associated with worse survival of hemodialysis patients independent of the serum ferritin level.

INTRODUCTION: Ferritin level and erythropoiesis-stimulating agent (ESA) responsiveness are each associated with hemodialysis patient survival. We assessed interrelationships between these two vs. survival. METHODS: Patients in the Japan Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-2018) were included. All-cause mortality associations were assessed with progressive adjustment to evaluate covariate influence. RESULTS: During follow-up (median 2.6 years), 773 of 5154 patients died. After covariate adjustment, the mortality hazard ratio (HR) was 0.99 (95% CI: 0.81, 1.20) for low serum ferritin and 1.12 (CI: 0.89, 1.41) for high serum ferritin. By contrast, mortality risk with elevated ESA resistance index (ERI) persisted after covariate adjustment (HR 1.44, CI [1.17-1.78]). The serum ferritin and ERI interaction was not significant; p > 0.96 across all models. CONCLUSIONS: Japanese hemodialysis patients with high ERI experienced worse survival independent of serum ferritin levels, highlighting the importance of identifying and mitigating ESA hyporesponsiveness among dialysis patients.

Association of Nutritional Risk Index With Infection-Related Hospitalization and Death After Hospitalization in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVE: Patients undergoing dialysis frequently experience hospitalization due to cardiovascular disease (CVD) and infection. This population is also at high risk of rehospitalization and subsequent death. In addition to serious outcomes, hospitalization incurs substantial medical cost. Prevention of hospitalization is accordingly an urgent matter. Here, we examined whether nutritional disorder was associated with hospitalization and subsequent death. METHODS: The study was conducted under a prospective design using data from the Japanese Dialysis Outcomes and Practice Pattern Study. The exposure was the Nutritional Risk Index for Japanese Hemodialysis (NRI-JH), through which patients were divided into low-, medium-, and high-risk groups, with the low-risk group as referent. The primary outcome was CVD-related or infection-related hospitalization. Secondary outcome was all-cause mortality. For exploratory analyses, the associations of baseline or latest NRI-JH just before hospitalization, with death after hospitalizations, were examined. RESULTS: Of 4021 patients, 566 patients had CVD-related hospitalization and 375 had infection-related hospitalization during a median follow-up of 2.6 years. NRI-JH at baseline was significantly associated with infection-related hospitalization but not with CVD-related hospitalization, in multivariable Cox models (hazard ratio [HR] 1.46, 95% confidential interval [CI]: 1.09 to 1.97, P = .012 for medium-risk vs. low-risk group) (HR 2.46, 95% CI: 1.81 to 3.35, P < .001 for high-risk vs. low-risk group). NRI-JH was also associated with all-cause mortality. In addition, the baseline and latest high-risk NRI-JH groups were significantly associated with death after both CVD-related and infection-related hospitalizations. CONCLUSIONS: A higher nutritional risk as evaluated by NRI-JH was associated with infection-related hospitalization but not with CVD-related hospitalization. However, NRI-JH was significantly associated with death after both CVD-related and infection-related hospitalizations, suggesting that nutritional risk may be separately involved in hospitalization or subsequent death. NRI-JH may be useful in the planning of individual care to improve outcomes.

Association Between Disturbed Serum Phosphorus Levels and QT Interval Prolongation.

Introduction: QT interval prolongation is a risk factor for fatal arrhythmias and other cardiovascular complications. QT interval prolongation in patients on hemodialysis (HD) is not well understood. Hypocalcemia is a suspected, but poorly verified etiology in these patients, and the association between serum phosphorus levels and QT interval prolongation is unknown. We sought to determine the prevalence of QT interval prolongation in patients on HD and to verify the association between predialysis serum calcium (Ca) and phosphate (P) levels and QT interval prolongation. Methods: A cross-sectional study was conducted on adult patients on maintenance HD who were enrolled in the Japanese Society for Dialysis Therapy and Renal Data Registry 2019. After assessing patient characteristics, linear regression analysis was performed with predialysis serum Ca and P levels as exposures and a rate-corrected QT (QTc) interval as the outcome. Results: A total of 204,530 patients were analyzed with a mean QTc of 451.2 (standard deviation, 36.9) ms. After multivariable analysis, estimated change in QTc (coefficients; 95% confidence interval) per 1 mg/dl increase in serum Ca and P was -2.02 (-3.00 to -1.04) and 5.50 (3.92-7.09), respectively. In the restricted cubic spline curve, estimated change in QTc increased with lower values of serum Ca. The correlation between serum P and QTc showed a U-shaped curve. Conclusion: Decreased serum Ca levels and decreased and increased serum P levels may be associated with QT interval prolongation in patients on maintenance HD.

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 characterized 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 who received maintenance dialysis in 2018 as represented in the JSDT Renal Data Registry database (n = 227,136). EXPOSURE: Dialysis vintage categorized as: 0-<5 years, 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years. OUTCOME: 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, 5,510 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%, and the rate of being bedridden was 6.4%. Compared with<5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with frailty (APR, 1.06 [95% CI, 1.05-1.08], 1.10 [95% CI, 1.08-1.11], 1.14 [95% CI, 1.10-1.17], and 1.67 [95% CI, 1.60-1.73]), respectively. Compared with<5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with being bedridden (APR, 1.17 [95% CI, 1.13-1.22], 1.26 [95% CI, 1.20-1.31], 1.17 [95% CI, 1.08-1.26], and 1.66 [95% CI, 1.49-1.86], respectively. LIMITATIONS: Patients receiving short-term dialysis may have more unmeasured comorbidities compared with patients receiving long-term dialysis. CONCLUSIONS: Long-term dialysis therapy, particularly exceeding 30 years, is associated with deterioration of physical function and frailty. PLAIN-LANGUAGE SUMMARY: End-stage kidney disease increases the risk of frailty. Understanding how long-term dialysis affects physical function may help patients and caregivers plan their lives better. Our research explores the relationship between duration of maintenance dialysis and frailty. We found that longer durations of maintenance dialysis, especially longer than 30 years, were associated with a higher risk of frailty and being bedridden among Japanese patients. The factors responsible for these associations should be the focus of future research.

Current dialyzer classification in Japan and mortality risk in patients undergoing hemodialysis.

Dialyzers are classified into five types based on their ß2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a ß2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

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.