Visualization of intracellular ATP dynamics in different nephron segments under pathophysiological conditions using the kidney slice culture system.

ATP depletion plays a central role in the pathogenesis of kidney diseases. Recently, we reported spatiotemporal intracellular ATP dynamics during ischemia reperfusion (IR) using GO-ATeam2 mice systemically expressing an ATP biosensor. However, observation from the kidney surface did not allow visualization of deeper nephrons or accurate evaluation of ATP synthesis pathways. Here, we established a novel ATP imaging system using slice culture of GO-ATeam2 mouse kidneys, evaluated the ATP synthesis pathway, and analyzed intracellular ATP dynamics using an ex vivo IR-mimicking model and a cisplatin nephropathy model. Proximal tubules (PTs) were found to be strongly dependent on oxidative phosphorylation (OXPHOS) using the inhibitor oligomycin A, whereas podocytes relied on both OXPHOS and glycolysis using phloretin an active transport inhibitor of glucose. We also confirmed that an ex vivo IR-mimicking model could recapitulate ATP dynamics in vivo; ATP recovery in PTs after reoxygenation varied depending on anoxic time length, whereas ATP in distal tubules (DTs) recovered well even after long-term anoxia. After cisplatin administration, ATP levels in PTs decreased first, followed by a decrease in DTs. An organic cation transporter 2 inhibitor, cimetidine, suppressed cisplatin uptake in kidney slices, leading to better ATP recovery in PTs, but not in DTs. Finally, we confirmed that a mitochondria protection reagent (Mitochonic Acid 5) delayed the cisplatin-induced ATP decrease in PTs. Thus, our novel system may provide new insights into the energy dynamics and pathogenesis of kidney disease.

Knowledge of hepatitis B infection, hepatitis B vaccine, and vaccination status with its associated factors among healthcare workers in Kampot and Kep Provinces, Cambodia.

BACKGROUND: Healthcare Workers (HCWs) are susceptible to hepatitis B virus (HBV) infection and are advised to receive vaccination. However, vaccination rates remain low in developing countries. There is little data concerning Hepatitis B (HepB) vaccination and information regarding HBV knowledge among HCWs in Cambodia. This study aimed to evaluate the knowledge of HBV infection, HepB vaccine, and vaccination status with its associated factors among HCWs in Cambodia. METHODS: A Cross-sectional study was conducted among HCWs in Kampot and Kep Provinces, Cambodia, from September to October 2023 using a questionnaire survey. A total of 261 HCWs were recruited from 1,309 individuals working in all 83 health facilities using systematic random sampling methods. Statistical analyses including the χ2-test and multivariate logistic regression were conducted to identify factors associated with vaccination among the participants. RESULTS: Among 259 participants, 62.9% showed good knowledge of HBV infection, and 65.6% demonstrated good knowledge of the HepB vaccine. 59.8% of the participants had received the HepB vaccine, while 40.2% remained unvaccinated. Analysis showed that HCWs working at Provincial Health Department/Operational Districts and Provincial Referral Hospital/Referral Hospitals were more likely to be vaccinated compared to those at Health Centers [AOR = 6.5; CI = 1.1-39.5, p = 0.0403; AOR = 2.8, CI = 1.0-7.8, p = 0.0412], respectively. Furthermore, individuals with good knowledge of the HBV infection and vaccine were more likely to receive the vaccine compared to those with inadequate knowledge [AOR = 6.3; CI = 3.3-12.3, p < .0001; AOR = 3.7, CI = 1.9-7.4, p = 0.0001], respectively. Within the unvaccinated HCWs, 32% reported high vaccine costs as a barrier, 33% mentioned workplace vaccine was not for adults, and 59% reported insufficient education on adult HepB vaccination. CONCLUSIONS: The HepB vaccination coverage among HCWs is at 59.8%, which is below the World Health Organization's (WHO) recommendation rate of 100%. Knowledge of HBV infection and HepB vaccine were good predictive factors for vaccination. The high cost of vaccine, workplace vaccine not for adults, and insufficient education on adult vaccination were found as barriers to vaccination. This study underscores the importance of providing education to HCWs on HBV infection and the HepB vaccine. Furthermore, it highlights the need for a policy that ensures free vaccination for HCWs.

Physician approval for pregnancy in patients with systemic lupus erythematosus showing only serological activity: A vignette survey study.

OBJECTIVE: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity. METHODS: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios. RESULTS: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months. CONCLUSIONS: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses.

Which factors influence the decision to perform Hartmann's reversal in various causative disease situations? A retrospective cohort study between 2006 and 2021.

AIM: Our aim was to investigate the predictive factors for Hartmann's reversal and to describe the differences in the rates and timings of Hartmann's reversal for various causative diseases. METHOD: In this multicentre retrospective cohort study patients who underwent Hartmann's procedure (HP) between 2006 and 2018 were enrolled. To describe the demographic patterns of Hartmann's reversal through to 2021, we analysed the cumulative incidence rate of Hartmann's reversal over time based on the Kaplan-Meier failure estimate. Multivariable Cox proportional hazard analysis was performed with cluster-adjusted robust standard errors to calculate hazard ratios (HRs) for the assessment of variables associated with colostomy reversal. RESULTS: Of 250 patients who underwent the index HP and survived to discharge, 112 (45%) underwent subsequent Hartmann's reversal (36% for malignant and 51% for benign disease). The causative diseases with the highest probability of colostomy reversal were trauma (85%) and diverticular disease (73%). Conversely, colostomy reversal was performed in only 16% for colonic volvulus and 17% for bowel ischaemia. Home discharge after index HP (HR 5.22, 95% CI 3.31-8.23) and a higher body mass index (HR 1.03, 95% CI 1.01-1.04) were associated with a higher probability of Hartmann's reversal, whereas older age, malignant disease and a history of cardiovascular and psychoneurological diseases were independently associated with a lower probability of colostomy reversal. CONCLUSION: The probability and timing of Hartmann's reversal varied considerably with the surgical indications for colostomy creation. Our results could help surgeons counsel patients and their families regarding stoma closure surgery to set realistic expectations.

Trends in Cardiovascular Risk Factors by Income Among Japanese Adults Aged 30-49 Years From 2017 to 2020: A Nationwide Longitudinal Cohort Study.

OBJECTIVE: Income is a major social determinant of cardiovascular health. However, individual-level evidence regarding the trends in cardiovascular risk factors by income level among young working-age adults is limited. We thus aimed to examine the trends in cardiovascular risk factors among men and women aged 30-49 years by their income levels. METHODS: This nationwide longitudinal study included Japanese adults aged 30-49 years, who annually participated in the national health screening program from 2017 to 2020. Modified Poisson regression models were used to investigate trends in the prevalence of cardiovascular risk factors (obesity, hypertension, diabetes, and dyslipidemia) according to tertiles of individuals' annual income, adjusting for potential confounders. RESULTS: Among 58 814 adults, 50 024 (85%) were men; the mean (SD) age was 42.1 (5.4) years. Over the study period, the low-income group consistently showed a higher prevalence of obesity, hypertension, and diabetes than the high-income group. The difference in the prevalence of these diseases, particularly hypertension, across income groups increased from 2017 to 2020 among both men (low-income vs high-income: +5.73% [95% CI, 4.72-6.73] in 2017 and +8.26% [95% CI, 7.11-9.41] in 2020) and women (low-income vs high-income: +2.53% [95% CI, 0.99-4.06] in 2017 and +3.83% [95% CI, 1.93-5.73] in 2020). CONCLUSION: Among adults aged 30-49 years in Japan, a country with a universal healthcare coverage system, we found an increase in the gap of cardiovascular risk factors by income levels over the last 4 years. Careful monitoring of the increasing social disparities is needed to achieve cardiovascular health equity at this life stage.

Effect of Nudge-Based Intervention on Adherence to Physician Visit Recommendations and Early Health Outcomes among Individuals Identified with Chronic Kidney Disease in Screens.

BACKGROUND: Although CKD screening programs have been provided in many settings, little is known as to how we can effectively translate those screening programs into improved health. METHODS: We conducted a randomized clinical trial on national health screening for CKD in Japan between April 2018 and March 2019. A total of 4011 participants in CKD screening programs aged 40-63 years were randomly assigned to two interventions or the control, with a ratio of 2:2:1, respectively: (1) the nudge-based letter that contained a message on the basis of behavioral economics, (2) the clinical letter including general information about CKD risks, and (3) the control (informed only of the screening results). The main outcome was adherence to a recommended physician visit within 6 months of the intervention. The secondary outcomes were eGFR, proteinuria, and BP 1 year after the intervention. RESULTS: Compared with the control group, the probability of undergoing a recommended physician visit was higher among participants who received the nudge-based letter (19.7% for the intervention group versus 15.8% for the control; difference, +3.9 percentage points [pp]; 95% CI, +0.8 to +7.0; P=0.02) and the clinical letter (19.7% versus 15.8%; difference, +3.9 pp; 95% CI, +0.8 to +7.0; P=0.02). We found no evidence that interventions were associated with improved early health outcomes. CONCLUSIONS: The behavioral economics intervention tested in this large RCT had limited effect on changing behavior or improving health outcomes. Although the approach has promise, this study demonstrates the challenge of developing behavioral interventions that improve the effectiveness of CKD screening programs.Clinical Trial registry name and registration number: University Hospital Medical Information Network Clinical Trial Registry, UMIN000035230.

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients.

BACKGROUND: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. METHODS: Serial protocol biopsy samples (0 hour, 1, 6, and 12 months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. RESULTS: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy, and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared with patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pretransplantation rituximab treatment dramatically attenuated the development of stage II TLTs. CONCLUSIONS: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.

Lineage tracing analysis defines erythropoietin-producing cells as a distinct subpopulation of resident fibroblasts with unique behaviors.

Erythropoietin (Epo) is produced by a subpopulation of resident fibroblasts in the healthy kidney. We have previously demonstrated that, during kidney fibrosis, kidney fibroblasts including Epo-producing cells transdifferentiate into myofibroblasts and lose their Epo-producing ability. However, it remains unclear whether Epo-producing cells survive and transform into myofibroblasts during fibrosis because previous studies did not specifically label Epo-producing cells in pathophysiological conditions. Here, we generated EpoCreERT2/+ mice, a novel mouse strain that enables labeling of Epo-producing cells at desired time points and examined the behaviors of Epo-producing cells under pathophysiological conditions. Lineage-labeled cells that were producing Epo when labeled were found to be a small subpopulation of fibroblasts located in the interstitium of the kidney, and their number increased during phlebotomy-induced anemia. Around half of lineage-labeled cells expressed Epo mRNA, and this percentage was maintained even 16 weeks after recombination, supporting the idea that a distinct subpopulation of cells with Epo-producing ability makes Epo repeatedly. During fibrosis caused by ureteral obstruction, EpoCreERT2/+-labeled cells were found to transdifferentiate into myofibroblasts with concomitant loss of Epo-producing ability, and their numbers and the proportion among resident fibroblasts increased during fibrosis, indicating their high proliferative capacity. Finally, we confirmed that EpoCreERT2/+-labeled cells that lost their Epo-producing ability during fibrosis regained their ability after kidney repair due to relief of the ureteral obstruction. Thus, our analyses have revealed previously unappreciated characteristic behaviors of Epo-producing cells, which had not been clearly distinguished from those of resident fibroblasts.

No Healthcare Utilization and Death.

BACKGROUND: An inappropriately low frequency of healthcare utilization has been reported to be associated with poor control of chronic diseases, accelerating healthcare disparities. However, the evidence is limited regarding the association between no healthcare utilization and mortality. OBJECTIVES: To examine whether individuals without healthcare utilization have the increased risks of mortality among the US general population. DESIGN: Prospective cohort study PARTICIPANTS: Adults aged ≥ 20 years (n = 39,067) in the National Health and Nutrition Examination Survey (NHANES)1999-2014 linked to national mortality data through December 2015. MAIN MEASURES: The exposure was the number of visits to healthcare providers during the past year (healthcare utilization): none, 1-3 times (referent), 4-9 times, or ≥ 10 times. Cox hazard regression models were employed to estimate the adjusted hazard ratios (aHR) of all-cause, cardiovascular, and cancer mortality adjusting for socio-demographic characteristics and comorbidities. KEY RESULTS: During a median follow-up of 7.4 years, participants without visit over the past year showed higher risks of all-cause mortality (aHR [95% CI] = 1.16 [1.04-1.30]) and cardiovascular mortality (aHR [95% CI] = 1.62 [1.28-2.05]) than those who visited the office 1-3 times. We found no evidence of the association between no visit and cancer mortality. The association between no providers' office visit and all-cause mortality was stronger among males (aHR [95% CI] = 1.22 [1.06-1.40]) than females (aHR [95% CI] = 0.97 [0.79-1.19]; p-for-interaction = 0.01) and among uninsured individuals (aHR [95% CI] = 1.22 [0.98-1.51]) than insured individuals (aHR [95% CI] = 1.09 [0.95-1.25]; p-for-interaction = 0.04). CONCLUSION: No providers' office visit over a year was associated with increased risks of all-cause and cardiovascular mortality. Further investigations are warranted to identify the underlying reasons for the elevated mortality risks due to no healthcare utilization.

High variability in results and methodological quality among overlapping systematic reviews on the same topics in surgery: a meta-epidemiological study.

BACKGROUND: Redundant publication of systematic reviews and meta-analyses (SRs/MAs) on the same topic presents an increasing burden for clinicians. The aim of this study was to describe variabilities in effect size and methodological quality of overlapping surgery-related SRs/MAs and to investigate factors associated with their postpublication citations. METHODS: PubMed/MEDLINE was searched to identify SRs/MAs of RCTs on thoracoabdominal surgeries published in 2015. Previous SRs/MAs on the same topics published within the preceding 5 years (2011-2015) were identified and 5-year citation counts (through to 2020) were evaluated. Discrepancies in pooled effect sizes and their methodological quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR) among overlapping SRs/MAs were assessed. The SR/MA-level factors associated with 5-year citation counts were explored, using a mixed-effects regression model with a random intercept for surgical topics. RESULTS: A total of 57 surgery-related SRs/MAs (48 topics) published in 2015 were identified, and 146 SRs/MAs had overlapping publications on 29 topics (60.4 per cent of all topics) in the preceding 5 years. There was considerable variability in methodological quality of SRs/MAs and coverage probability for relevant RCTs, resulting in discrepant effect size estimates for the same topic. High quality (AMSTAR score 8-11) was independently associated with higher 5-year citation counts (coefficient = 32.82; 95 per cent c.i. 15.63 to 50.02; P < 0.001). CONCLUSION: Overlapping SRs/MAs with high variability in results and methodological quality were common in surgery. A high-quality SR/MA score was an independent predictor of more frequent citations. Researchers and journal editors should concentrate their efforts on limiting publications to higher-quality reviews.

Changes in Drug Utilization After Publication of Clinical Trials and Drug-Related Scandals in Japan: An Interrupted Time Series Analysis, 2005-2017.

BACKGROUND: Breaches of ethics undermine the practice of medicine. In Japan, two major scandals involving clinical research and drug marketing occurred after the publication of clinical trials. To study the effects of those scandals, we evaluated changes in the use of first-generation angiotensin II receptor blockers (ARBs) after publication of relevant clinical trials and also after the subsequent scandals. METHODS: We conducted a quasi-experimental design of an interrupted time series analysis (ITSA) on nationwide monthly drug-market data covering 12 years (2005 to 2017) in Japan. The main outcome was the use of first-generation ARBs (valsartan, candesartan, and losartan). The two exposures were the publication of ARB-related clinical-trial results (October 2006) and subsequent ARB-related scandals involving research and marketing (February 2013). A generalized estimating equation model was fitted for ITSA with a log link, Poisson distribution, robust variance estimators, and seasonality adjustment. RESULTS: The publication of clinical trials was associated with 12% increase in the use of first-generation ARBs in Japan, and the subsequent ARB-related scandals was associated with 19% decrease. The decrease in the use of first-generation ARBs after the scandals was greater than the increase in their use after the publication of clinical-trial results. The net effect of the two exposures was a 9% decrease in the use of first-generation ARBs. CONCLUSIONS: The scandals were associated with decrease in the use of first-generation ARBs, and that decrease was greater than the increase associated with the publication of "successful" clinical trials, making the net effect not zero but negative.

Sagittal imbalance and symptoms of depression in adults: Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS).

PURPOSE: With spinal deformities, mental health can deteriorate due to sagittal imbalance of the spine. The purpose of this study was to clarify the relationship between sagittal imbalance and symptoms of depression among local residents in the community. METHODS: This study used data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS) in 2010. The sagittal vertical axis (SVA) was identified as an indicator of sagittal imbalance. Symptoms of depression were assessed using the 5-item version of the Mental Health Inventory. Participants were classified into three categories based on the SVA balance as normal (< 40 mm), moderate imbalance (40-95 mm), and severe imbalance (> 95 mm). To evaluate the relationship between sagittal imbalance of the spine and symptoms of depression, the adjusted risk ratio (RR) and the 95% confidence interval (CI) were calculated using a generalized linear model with Poisson link. RESULTS: There were 786 participants included in the statistical analysis. Overall, the mean age was 68.1 y (standard deviation, 8.8 y), and 39.4% were men. The prevalence of symptoms of depression by SVA category was 18.6% for normal, 23.8% for moderate, and 40.6% for severe. On multivariate analysis, the RR of SVA for symptoms of depression compared to the normal category was 1.12 (95% CI 0.7-1.70) for the moderate category and 2.29 (95% CI 1.01-5.17) for the severe category. CONCLUSION: In local community residents, sagittal imbalance had a significant association with symptoms of depression.

Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis.

BACKGROUND: Depletion of ATP in renal tubular cells plays the central role in the pathogenesis of kidney diseases. Nevertheless, inability to visualize spatiotemporal in vivo ATP distribution and dynamics has hindered further analysis. METHODS: A novel mouse line systemically expressing an ATP biosensor (an ATP synthase subunit and two fluorophores) revealed spatiotemporal ATP dynamics at single-cell resolution during warm and cold ischemic reperfusion (IR) with two-photon microscopy. This experimental system enabled quantification of fibrosis 2 weeks after IR and assessment of the relationship between the ATP recovery in acute phase and fibrosis in chronic phase. RESULTS: Upon ischemia induction, the ATP levels of proximal tubule (PT) cells decreased to the nadir within a few minutes, whereas those of distal tubule (DT) cells decreased gradually up to 1 hour. Upon reperfusion, the recovery rate of ATP in PTs was slower with longer ischemia. In stark contrast, ATP in DTs was quickly rebounded irrespective of ischemia duration. Morphologic changes of mitochondria in the acute phase support the observation of different ATP dynamics in the two segments. Furthermore, slow and incomplete ATP recovery of PTs in the acute phase inversely correlated with fibrosis in the chronic phase. Ischemia under conditions of hypothermia resulted in more rapid and complete ATP recovery with less fibrosis, providing a proof of concept for use of hypothermia to protect kidney tissues. CONCLUSIONS: Visualizing spatiotemporal ATP dynamics during IR injury revealed higher sensitivity of PT cells to ischemia compared with DT cells in terms of energy metabolism. The ATP dynamics of PTs in AKI might provide prognostic information.

Developmental stages of tertiary lymphoid tissue reflect local injury and inflammation in mouse and human kidneys.

Tertiary lymphoid tissues (TLTs) are inducible ectopic lymphoid tissues in chronic inflammatory states and function as sites of priming local immune responses. We previously demonstrated that aged but not young mice exhibited multiple TLTs after acute kidney injury and that TLTs were also detected in human aged and diseased kidneys. However, the forms of progression and the implication for kidney injury remain unclear. To clarify this we analyzed surgically resected kidneys from aged patients with or without chronic kidney disease as well as kidneys resected for pyelonephritis, and classified TLTs into three distinct developmental stages based on the presence of follicular dendritic cells and germinal centers. In injury-induced murine TLT models, the stages advanced with the extent of kidney injury, and decreased with dexamethasone accompanied with improvement of renal function, fibrosis and inflammation. Kidneys from aged patients with chronic kidney disease consistently exhibited more frequent and advanced stages of TLTs than those without chronic kidney disease. Kidneys of patients with pyelonephritis exhibited more frequent TLTs with more advanced stages than aged kidneys. Additionally, TLTs in both cohorts shared similar locations and components, suggesting that TLT formation may not be a disease-specific phenomenon but rather a common pathological process. Thus, our findings provide the insights into biological features of TLT in the kidney and implicate TLT stage as a potential marker reflecting local injury and inflammation.

Quality of Care in Chronic Kidney Disease and Incidence of End-stage Renal Disease in Older Patients: A Cohort Study.

BACKGROUND: The quality of care received by a growing number of older patients with chronic kidney disease (CKD) has not been adequately examined. OBJECTIVE: The objective of this study was to assess the quality of CKD care among older patients and to clarify its association with the incidence of end-stage renal disease (ESRD). RESEARCH DESIGN: This was a population-based cohort study. SUBJECTS: Older (65 y and above) CKD patients diagnosed between October 2010 and September 2014 from the National Database of Health Insurance Claims of Japan. MEASURES: A composite quality score (QS) of 3 quality measures for CKD care during the 6 months after CKD diagnosis was computed. The validated quality measures included urine testing for proteinuria, nutritional guidance, and nonsteroidal anti-inflammatory drugs avoidance. To assess the association between the QS and ESRD incidence, we used instrumental variable analysis after stratification for the history of diabetes. RESULTS: Among the 890,773 older CKD patients, 2.9% progressed to ESRD (incidence rate of 12.5 per thousand person-years). In total, 59.9% underwent urine testing, 4.5% received nutritional guidance, and 91.2% avoided regular use of nonsteroidal anti-inflammatory drugs. An instrumental variable analysis revealed that a higher QS was associated with-lower ESRD incidence in patients diagnosed with diabetes (hazard ratio: 0.25, 95% confidence interval: 0.24-0.27 for each point higher score) but not in patients without a diagnosis of diabetes (hazard ratio: 0.99, 95% confidence interval: 0.92-1.05). CONCLUSION: Among older CKD patients, quality of CKD care varied between patients, and better quality of CKD care was associated with a lower ESRD incidence in patients with diabetes but not in nondiabetic patients.

Changes in Quality of Life in Older Hemodialysis Patients: A Cohort Study on Dialysis Outcomes and Practice Patterns.

BACKGROUND: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. METHODS: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009-2011) and 5 (2012-2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60-69, 70-79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. RESULTS: Hemodialysis patients aged 70-79 years and ≥80 years had lower PCS scores than those aged 60-69 years (median: 70-79 years = 43.1; interquartile range [IQR], 35.2-49.4; ≥80 years = 38.8; IQR, 31.6-43.8; 60-69 years = 45.4; IQR, 37.5-51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70-79 years = 45.6; IQR, 38.4-53.7; ≥80 years = 45.4; IQR, 36.9-55.1; 60-69 years = 46.8; IQR, 39.5-55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years' follow-up. CONCLUSIONS: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients.

Relationship between serum calcium or phosphate levels and mortality stratified by parathyroid hormone level: an analysis from the MBD-5D study.

INTRODUCTION: There is limited evidence about the association between calcium and phosphate levels and mortality stratified by intact parathyroid hormone (iPTH) level. METHODS: We investigated whether differences in iPTH level affect the relationship between calcium and phosphate levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism (SHPT). Calcium and phosphate levels were categorized as low (< 8.5 mg/dL, < 4.0 mg/dL), medium (≥ 8.5-< 9.5 mg/dL, ≥ 4.0-< 7.0 mg/dL), and high (≥ 9.5 mg/dL, ≥ 7.0 mg/dL), respectively. iPTH levels were grouped into < 300 or ≥ 300 pg/mL. Adjusted incidence rate ratios (aIRRs) were analyzed by weighted Poisson regression. RESULTS: For calcium, patients with higher iPTH (≥ 300 pg/mL) had significantly higher all-cause mortality rates in the high than in the medium category (aIRR 1.99, 95% confidence interval [CI] 1.16-3.42), and tended to have a higher mortality rate in the low category (aIRR 2.04, 95% CI 0.94-4.42). Patients with lower iPTH (< 300 pg/mL) had higher mortality rates in the high than in the medium category (aIRR 1.65, 95% CI 1.39-1.96). For phosphate, the mortality rate was significantly higher in the high than in the medium category in patients with higher and lower iPTH (aIRR 3.23, 95% CI 1.63-6.39 for iPTH ≥ 300 pg/mL; aIRR 1.58, 95% CI 1.06-2.36 for iPTH < 300 pg/mL). CONCLUSION: High calcium and phosphate levels were associated with increased risk of mortality irrespective of iPTH level.

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey.

AIM: After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. METHODS: We conducted a cohort study of residents aged 40-90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. RESULTS: Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03-1.86). CONCLUSION: This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

Length of hospital stay is associated with a decline in activities of daily living in hemodialysis patients: a prospective cohort study.

BACKGROUND: The impact of length of hospital stay on activities of daily living (ADLs) has not specifically been investigated among dialysis patients. Therefore, we attempt to verify the association between the length of hospital stay and the decline in ADLs among hemodialysis patients. METHODS: This prospective cohort study used data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS). We included 2442 hemodialysis patients aged ≥40 years from the J-DOPPS phase V (2012-2015) and subsequently excluded those who had already lost basic activities of daily living (BADLs) as demonstrated by dependency in at least three of the five BADLs at baseline and for whom changes in ADLs had been evaluated for less than 90 days. The main exposure was the cumulative length of hospital stay during the follow-up period. The primary outcomes were a decline in at least one of the five BADLs and eight instrumental activities of daily living (IADLs). We compared risk ratios (RRs) for 30-day increments for hospital stays with 10-year increments for age and having diabetes. RESULTS: A total of 849 patients were included in the statistical analysis. The cumulative length of hospital stay was significantly associated with a risk of decline in ADLs (adjusted RRs [95% confidence intervals] per 30-day increments: 1.42 [1.15 to 1.75] for BADLs, 1.38 [1.13 to 1.68] for IADLs). The adjusted RRs [95% CI] for 10-year increments in age were 1.20 [0.96 to 1.50] and 1.21 [1.00 to 1.47]. The adjusted RRs [95% CI] for having diabetes were 1.36 [0.97 to 1.91] for BADLs and 1.38 [1.04 to 1.84] for IADLs. CONCLUSION: The impact of a 30-day increment in the cumulative length of hospital stay on the decline in ADLs was comparable to that of a 10-year increase in age and having diabetes.

Changes in 3-month mineral and bone disorder patterns were associated with all-cause mortality in prevalent hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: There is limited evidence on the association between short-term changes in mineral and bone disorder parameters and survival in maintenance hemodialysis patients. METHODS: We investigated the association between changing patterns of phosphorus, calcium and intact parathyroid hormone levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism. Each parameter was divided into three categories (low [L], middle [M] and high [H]), and the changing patterns between two consecutive visits at 3-month intervals were categorized into nine groups (e.g., L-L and M-H). The middle category was defined as 4.0-7.0 mg/dL for phosphorous, 8.5-9.5 mg/dL for calcium and 200-500 pg/mL for intact parathyroid hormone. Adjusted incidence rates and rate ratios were analyzed by weighted Poisson regression models accounting for time-dependent exposures. RESULTS: For phosphorus, shifts from low/high to middle category (L-M/H-M) were associated with a lower mortality compared with the L-L and H-H groups, whereas shifts from middle to low/high category (M-L/M-H) were associated with a higher mortality compared with the M-M group. For calcium, shifts from low/middle to high category (L-H/M-H) were associated with a higher mortality compared with the L-L and M-M groups, whereas shifts from high to middle category (H-M) were associated with a lower mortality compared with the H-H group. For intact parathyroid hormone, shifts from low to middle category (L-M) were associated with a lower mortality compared with the L-L group. CONCLUSIONS: Changes in the 3-month patterns of phosphorus and calcium toward the middle category were associated with lower mortality. Our study also suggests the importance of avoiding hypercalcemia.