The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study.

INTRODUCTION: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. METHODS: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. RESULTS: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57). CONCLUSIONS: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.

Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan.

INTRODUCTION: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. METHODS: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006-2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. RESULTS: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) - 1.30 (1.20-1.41), 1.56 (1.39-1.76), and 2.15 (1.77-2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. CONCLUSION: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.

Newspaper Campaign to Promote Deceased Organ Donation: Who Can Appeal to the General Japanese Population?

BACKGROUND: Various interventions are reportedly effective in promoting organ donor registration. However, the identity of those who best serve as presenters to appeal to the general public is not known. METHODS: A campaign for organ donor registration was conducted through a local newspaper advertisement in Japan. The advertisement appeared in 439,733 copies of the newspaper on January 9, 2021. In addition to the main message, 6 different presenters with photos of their faces and quick response codes were listed in the advertisement, namely a urologist, transplant physician, nephrologist, dialysis physician, ophthalmologist, and kidney transplant recipient who was a nephrologist himself (ie, a recipient and nephrologist). Newspaper readers watched each video about deceased organ donation via the quick response codes, and the number of video views acquired 30 days after the appearance was the main outcome, which was assessed using YouTube analytics. The proportions (95% CI) of people who watched each video among 439,733 newspaper readers were compared among the 6 presenters. RESULTS: The analyzed videos were viewed 262 times. The video produced by the recipient and nephrologist had the highest number of views among the 6 presenters (proportion: 0.019% [95% CI, 0.015-0.023]), followed by the one produced by the dialysis physician (0.011% [95% CI, 0.008-0.014]), the nephrologist (0.010% [95% CI, 0.007-0.014]), the urologist (0.008% [95% CI, 0.006-0.012]), the transplant physician (0.006% [95% CI, 0.004-0.009]), and the ophthalmologist (0.005% [95% CI, 0.004-0.008]). CONCLUSIONS: The appeal by the recipient and the nephrologist reached the highest proportion of people who watched the video about deceased organ donation in Japan.

Association between serum alkaline phosphatase and bacteraemia in haemodialysis outpatients: a multicentre retrospective cross-sectional study.

OBJECTIVES: Elevated baseline serum alkaline phosphatase (ALP) may correlate with higher medium-term to long-term mortality in the general population and in patients with chronic kidney disease. However, few data are available on the association between serum ALP and the short-term prognosis of patients on haemodialysis (HD). We verified the association of ALP levels and bacteraemia or death in maintenance HD patients suspected of bacteraemia in an outpatient setting. DESIGN: We analysed 315 consecutive HD patients suspected of having bacteraemia with two sets of blood culture drawn on admission. SETTING: Admission to two tertiary-care university medical centres from January 2013 to December 2015. PARTICIPANTS: Consecutive cases on maintenance HD aged≥18 years. Cases of hospitalised patients who had been transferred from another hospital, had a dialysis vintage<2 months, were also undergoing peritoneal dialysis, and/or were receiving HD less than once a week were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was bacteraemia and secondary outcome was in-hospital death. RESULTS: Among 315 cases included in the study, 187 had baseline-measured ALP levels, with a cut-off value on ROC analysis of 360 U/L (Area Under the Curve (AUC) 0.60, sensitivity 0.49, specificity 0.76). In multivariate analysis, there was a statistically significant association between a higher ALP in hospital visit and bacteraemia (OR: 2.37, 95% CI: 1.17 to 4.83). However, there were no statistically significant associations between higher ALP and in-hospital death (OR: 1.20, 95% CI: 0.57 to 2.54). A sensitivity analysis of 187 patients with no missing ALP values also demonstrated a significant association between elevated ALP and bacteraemia, but no significant association between ALP and in-hospital death. CONCLUSIONS: Elevated ALP is a predictor of bacteraemia. In HD patients suspected of bacteraemia in outpatient settings, increased ALP levels were associated with increased likelihood of confirmed disease.

Association between the transtheoretical model approach and sustained intradialytic pedaling exercise: A retrospective cohort study.

ABSTRACT: The transtheoretical model (TTM) is a promising approach to the promotion of behavior change, but it remains to be established whether there is an association between the TTM approach and intradialytic exercise among patients on hemodialysis (HD) with low motivation to exercise in a real-world setting.This retrospective cohort study, conducted in a regional hospital in Japan, included adult outpatients receiving HD 3 times per week who had never participated in intradialytic pedaling exercise despite the encouragement of the HD personnel. Patients were divided into 2 groups according to HD weekday. Patients undergoing HD on Tuesday, Thursday, and Saturday were encouraged by the HD unit team to exercise during HD based on the TTM (exposure group) and those receiving HD on Monday, Wednesday, and Friday were encouraged to exercise as usual (control group). The primary outcome was sustained intradialytic exercise using a leg ergometer, defined as a total of 72 sessions of 30-minute pedaling exercise (duration of at least 6 months).Overall, 85 patients were included in the analysis (mean age: 67.1 ±â€Š11.9 years, 22% female). Of 33 patients in the exposure group, 10 (30%) maintained intradialytic exercise, compared with 2 of 52 patients (4%) in the control group. Log-binomial regression models with stabilized inverse probability of treatment weighting showed a significant association between the TTM approach and sustained intradialytic exercise (adjusted risk ratio 9.23 [95% confidence interval 2.13-40.00]). There were no exercise-related cardiovascular events.Among patients with low motivation to exercise during HD, use of the TTM approach in clinical practice was associated with sustained intradialytic exercise compared with usual care.

Living-Donor Kidney Transplantation Performed in a Low-Volume Center by Visiting Surgeons From a High-Volume Center and Managed Clinically Solely by Nephrologists: 1-Year Outcomes.

BACKGROUND: Little is known about the outcome of living-donor kidney transplantation (LDKT) performed in low-volume centers lacking the services of full-time transplant surgeons. This retrospective cohort study assessed the outcome of LDKT performed in a low-volume center by visiting transplant surgeons from a high-volume center and managed perioperatively by transplant nephrologists. METHODS: We compared Japanese adult patients who had no donor-specific antibodies and underwent LDKT between 2006 and 2015 either in a low-volume (n = 31) or high-volume (n = 481) center. In the low-volume center, visiting transplant surgeons from the high-volume center conducted LDKT and transplant nephrologists managed the recipients peri- and postoperatively. The primary outcome was the composite of infection, cardiovascular disease, or cancer during 1-year follow-up. The outcomes of the low- and high-volume centers were compared using 1:2 propensity score matching. RESULTS: After matching, 9 of 29 patients in the low-volume center (31.0%) and 16 of 58 patients in the high-volume center (27.6%) experienced the primary composite outcome (risk ratio = 1.13; 95% confidence interval, 0.57-2.23). There were no significant differences between the 2 groups in graft function at 1 year, all-cause graft loss, biopsy-proven rejection, and urological complications. However, the median duration of post-LDKT hospitalization was significantly longer in the low-volume center than in the high-volume center (23 and 16 days, respectively). CONCLUSIONS: Among Japanese patients without preformed donor-specific antibodies, LDKT conducted at a low-volume center by visiting transplant surgeons from a high-volume center and managed clinically by transplant nephrologists was not associated with significantly higher risk of postoperative complications.

Added value of clinical prediction rules for bacteremia in hemodialysis patients: An external validation study.

INTRODUCTION: Having developed a clinical prediction rule (CPR) for bacteremia among hemodialysis (HD) outpatients (BAC-HD score), we performed external validation. MATERIALS & METHODS: Data were collected on maintenance HD patients at two Japanese tertiary-care hospitals from January 2013 to December 2015. We enrolled 429 consecutive patients (aged ≥ 18 y) on maintenance HD who had had two sets of blood cultures drawn on admission to assess for bacteremia. We validated the predictive ability of the CPR using two validation cohorts. Index tests were the BAC-HD score and a CPR developed by Shapiro et al. The outcome was bacteremia, based on the results of the admission blood cultures. For added value, we also measured changes in the area under the receiver operating characteristic curve (AUC) using logistic regression and Net Reclassification Improvement (NRI), in which each CPR was added to the basic model. RESULTS: In Validation cohort 1 (360 subjects), compared to a Model 1 (Basic Model) AUC of 0.69 (95% confidence interval [95% CI]: 0.59-0.80), the AUC of Model 2 (Basic model + BAC-HD score) and Model 3 (Basic model + Shapiro's score) increased to 0.8 (95% CI: 0.71-0.88) and 0.73 (95% CI: 0.63-0.83), respectively. In validation cohort 2 (96 subjects), compared to a Model 1 AUC of 0.81 (95% CI: 0.68-0.94), the AUCs of Model 2 and Model 3 increased to 0.83 (95% CI: 0.72-0.95) and 0.85 (95% CI: 0.76-0.94), respectively. NRIs on addition of the BAC-HD score and Shapiro's score were 0.3 and 0.06 in Validation cohort 1, and 0.27 and 0.13, respectively, in Validation cohort 2. CONCLUSION: Either the BAC-HD score or Shapiro's score may improve the ability to diagnose bacteremia in HD patients. Reclassification was better with the BAC-HD score.

Knowledge Does Not Correlate with Behavior toward Deceased Organ Donation: A Cross-Sectional Study in Japan.

BACKGROUND Although knowledge is an important factor that influences decisions regarding deceased organ donation, the associations of knowledge with attitude and behavior regarding organ donation remain uncertain in countries with low organ donation rates like Japan. MATERIAL AND METHODS We conducted a cross-sectional survey of hospital medical and non-medical staff in 15 Japanese medical facilities. The questionnaire included items on knowledge, attitude, and behavior toward deceased organ donation and transplantation. Participants were divided into 3 groups according to the tertile of knowledge score. Modified Poisson regression models were used for associations of knowledge score with organ donor registration and willingness to become an organ donor after death. RESULTS Of the 1967 staff, 1275 returned the questionnaires (response rate, 64.8%). There were 1190 study subjects with complete data for analysis. For the lowest (n=512), middle (n=428), and highest (n=250) tertile knowledge groups, the proportions of participants who registered and expressed willingness to donate organs were 20.1%, 23.4%, and 28.4% and 31.1%, 38.3%, and 44.0%, respectively. The adjusted proportion ratios for organ donor registration were 0.90 (95% CI, 0.73-1.10) for the middle and 1.00 (0.80-1.26) for the highest tertile of knowledge, compared with the lowest tertile. However, participants with the highest tertile of knowledge score expressed higher willingness for organ donation than the lowest tertile (adjusted proportion ratio, 1.37; 95% CI, 1.13-1.66). CONCLUSIONS For hospital staff in Japanese medical facilities, high knowledge about organ donation and transplantation was not associated with donor registration, but was associated with willingness to become an organ donor.

Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis.

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty-one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger's Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.

Author Reply to the Letter to the Editor: Antimicrobial stewardship without infectious disease physician.

We were pleased to read the letter to our article and decided to respond to the letter.

Antimicrobial stewardship without infectious disease physician for patients with candidemia: A before and after study.

BACKGROUND: Little is known about the effects of antimicrobial stewardship team (AST) without infectious disease physician (IDP) on clinical outcome in patients with candidemia. METHODS: We conducted a before and after study involving patients with hospital-acquired candidemia at a tertiary hospital without IDPs. The AST consisted of physicians, pharmacists, nurse, microbiologist, and administrative staff. A candidemia care bundle was developed based on the Infectious Disease Society of America (IDSA) guideline. The non-IDP AST provided recommendations to the attending physicians whose patients developed candidemia during hospitalization. The primary outcome was 30-day all-cause mortality, while the secondary outcomes were adherence to the IDSA guidelines regarding the management of candidemia. Data of up to 3 years of preintervention and 3 years of intervention period were analyzed. RESULTS: By 30 days, 11 of 46 patients (23.9%) in the intervention group and 7 of 30 patients (23.3%) in the preintervention group died (adjusted hazard ratio for the intervention group: 0.68 [95% CI 0.24-1.91]). The non-IDP AST was associated with appropriate empirical antifungal therapy (100% vs 60.0%; proportion ratio 1.67 [95% CI 1.24-2.23]), appropriate duration of treatment (84.7% vs 43.3%; 1.96 [1.28-3.00]), removal of central venous catheters (94.4% vs 70.8%; 1.33 [1.02-1.74]), and ophthalmological examination (93.5% vs 63.3%; 1.48 [1.12-1.96]). CONCLUSIONS: Although we found no significant difference in 30-day mortality, the non-IDP AST was associated with improved adherence to guidelines for management of candidemia.

Effects of structured education program on organ donor designation of nursing students and their families: A randomized controlled trial.

INTRODUCTION: Little is known about the effect of education programs on changing attitudes and behaviors of participants and their families toward deceased organ donation. METHODS: The subjects of this randomized trial were Japanese nursing students who were not previously designated organ donors. They were randomly assigned to either the education program or information booklet group. The program comprised a lecture followed by group discussion and information booklet. The primary outcome was self-reported organ donor designation. Outcomes were assessed by questionnaire. RESULTS: Data of 203 (99.0%) students were analyzed. At study end, seven of 102 students (6.9%) of the program group and one of 101 students (1.0%) of the booklet group consented to donate organs (proportion ratio 6.93 [95% CI 0.87-55.32]). There were significant between-group differences in willingness to consent for donation (54.9% vs 39.6%; proportion ratio 1.39 [95% CI 1.03-1.87]), family discussion (31.4% vs 15.9%; 1.98 [1.16-3.38]), and organ donor designation of family members (11.8% vs 2.0%; 5.94 [1.36-25.88]). No group differences were found in willingness for organ donation by students and family members. CONCLUSION: Although there were no significant between-group differences in organ donor designation, the program seems to indirectly promote consent to organ donation by their families.

Preferences of young physicians at community hospitals regarding academic research training through graduate school: a cross-sectional research.

BACKGROUND: Desire to attend graduate school for academic research training following the mandatory two-year clinical internship is unknown among young Japanese physicians who work at community hospitals after their internship. The aim of this study is to determine opinions and factors regarding pursuing higher education through graduate school among young physicians who work at community hospitals after their two-year internship. METHODS: This cross-sectional survey was conducted among young physicians working at community hospitals after their two-year internship. We examined the percentage of young physicians considering higher education through graduate school, the planned timing and field of enrollment among those wanting to enroll, and reasons for not continuing their education among those with no such plans. The association between desire to enroll in graduate school and background characteristics was examined using modified least-squares regression to estimate proportion difference. RESULTS: Among 127 (73.2% internal medicine specialists, median age 30 years) physicians in 33 hospitals, 71 (55.9%) stated that they wished to enroll in graduate school. The most frequently reported timing was 7-8 years after graduation from medical school. Those who stated no desire to attend graduate school cited concerns about the quality of training or not having enough knowledge to choose an appropriate laboratory or field, among other reasons. Increased number of years since graduating medical school [adjusted proportion difference (PD) -6.0%, 95% confidence interval (95% CI) -9.8 to -2.3%], being a woman with children [adjusted PD -53.4%, 95% CI -87.3 to -19.5% (vs. a man not having children)], and completing their two-year internship at both university and community hospitals [adjusted PD -40.3%, 95% CI -72.5 to -8.0% (vs. internship only at community hospitals)] were associated with a reduction in desire to enroll in graduate school. CONCLUSIONS: We identified a growing trend in desire among young physicians to attend graduate school. Attracting those young physicians who express no desire to attend graduate school, however, will require establishment of more flexible graduate school programs which address their concerns.

Effect of an educational program on attitudes towards deceased organ donation.

BACKGROUND: Organ shortage for transplantation remains a serious global issue. We assessed the effects of an educational program on changing attitudes of medical students towards deceased organ donation. MATERIAL AND METHODS: We conducted a non-randomized trial involving medical students who had not previously signed a donor card. Third-year medical students (n=86, program group) received an information pamphlet followed by a 60-min classroom lecture by a transplant physician who was himself a kidney transplant recipient and finally another information pamphlet containing a donor card. First-year students (n=87, control group) received the same two pamphlets only. The primary outcome was signing a donor card. The secondary outcomes included willingness to sign a donor card, willingness to donate organs, family discussion about deceased organ donation, and knowledge. Outcomes were measured by questionnaires before and after the intervention. RESULTS: A higher proportion of students of the program group signed a donor card than the pamphlet group (8.1% vs. 0%, respectively). After propensity score adjustment, the program was associated with higher proportion of willingness to sign a donor card (91.9% vs. 73.6%; adjusted proportion ratio 1.28 [95% CI 1.11-1.48]), family discussion (18.6% vs. 6.9%; 2.85 [1.15-7.03]), and increased knowledge. There were no significant differences between the two groups in willingness to donate organs after brain death (64.0% vs. 60.9%; 1.12 [0.90-1.40]) and cardiac death (77.9% vs. 71.3%; 1.11 [0.93-1.33]). CONCLUSIONS: The educational program delivered by a transplant physician and a recipient may alter the attitudes of medical students towards deceased organ donation.

High incidence of Aggregatibacter actinomycetemcomitans infection in patients with cerebral infarction and diabetic renal failure: a cross-sectional study.

BACKGROUND: Recent epidemiological studies suggest that periodontitis is a major risk factor for renal failure and cerebral infarction. The aim of this study was to evaluate the association among periodontitis, renal failure, and cerebral infarction, focusing on microbiological and immunological features. METHODS: Twenty-one patients treated with hemodialysis (HD) were enrolled in this study. They were 8 with diabetic nephropathy and 13 with non-diabetic nephropathy. Blood examination, periodontal examination, brain magnetic resonance image (MRI), and dental radiography were performed on all patients. Subgingival plaque, saliva, and blood samples were analyzed for the periodontal pathogens, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that the patients with diabetic nephropathy had more A. actinomycetemcomitans compared with non-diabetic nephropathy (P = 0.038) in dental plaque. Furthermore, the patients with diabetic nephropathy showed a significantly higher incidence of cerebral infarction compared with those with non-diabetic nephropathy (P = 0.029). Clinical oral and radiographic scores tended to be higher among patients in the diabetic nephropathy group than in the non-diabetic nephropathy group. CONCLUSIONS: Periodontal pathogens, particularly A. actinomycetemcomitans, may play a role, at least a part, in the development of cerebral infarction in Japanese HD patients with diabetic nephropathy.