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Abstract Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into “iron-based”, “only non-iron-based”, and “no use”. The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate.

Introduction Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population.Methods and analysis This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse.Ethics and dissemination The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals.Trial registration number jRCTs041220126.

Objectives: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular–renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. Methods: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular–renal events. Results: During the median follow-up period of 109 months, 221 patients developed cardiovascular–renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular–renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81–3.72) and 2.27 (95% CI, 1.82–2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23–29.42) of cardiovascular–renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p

Objectives: To examine the differences in antimicrobial selection outcomes in nursing and healthcare-associated pneumonia (NHCAP) patients with and without risk factors for drug-resistant pathogen (RDRP) infection, and to identify the cause of in-hospital death after improvement of NHCAP. Methods: We conducted a retrospective analysis of the medical records of hospitalized adult patients with NHCAP. NHCAP patients were divided into the RDRP and non-RDRP groups. The RDRP group was further classified into the narrow and broad subgroups according to the type of empirical antimicrobial agent selected. The difference in mortality between these subgroups was then examined. The cause of all in-hospital deaths was also evaluated. Results: We evaluated 220 patients with NHCAP. There was no difference in mortality between the narrow and broad subgroups (11.8% vs. 15.4%, p=0.655). Among the group with improved NHCAP, 11.3% (n=23/203) died in hospital before discharge. Although the causes of death in patients who improved after NHCAP were diverse, the most common was recurrence of pneumonia. Conclusions: Empirical antimicrobial therapy for NHCAP may not always require selection of broad-spectrum antimicrobial agents, as has been previously reported. Patients with NHCAP may die from other causes, even after NHCAP has improved.

Abstract Background Aortic valve stenosis (AS) has a high prevalence and poor prognosis in patients who receive maintenance dialysis. However, few large-scale observational studies in Japan have investigated patients with AS who underwent dialysis. In this study, we investigated the prevalence and factors associated with AS in Japanese patients who underwent dialysis. Methods In this cross-sectional analysis, we enrolled patients who underwent dialysis and transthoracic echocardiography between July 1, 2017 and June 30, 2018. Patients with a maximum aortic jet velocity (Vmax) ≥ 2.0 m/s, pressure gradient (PG) between the left ventricle and ascending aorta (mean PG) ≥ 20 mmHg, or aortic valve area (AVA) ≤ 1.0 cm2 were categorized into the AS group (G1). Patients with Vmax ≥ 3.0 m/s, mean PG ≥ 20 mmHg, or AVA ≤ 1.0 cm2 were categorized into the moderate and severe AS groups (G2). We performed multivariate logistic regression analysis and compared G1 and G2 with the non-AS group to determine the risk factors for AS. We also investigated the risk factors for aortic valve calcification, which is a pre-stage for AS. Results Of the 2,786 patients investigated, 555 (20.0%) and 193 (6.9%) were categorized into G1 and G2, respectively. Multivariate logistic regression analysis revealed that age, long-term dialysis, and elevated serum phosphorus levels were associated with AS in both the groups (p 6.0 mg/dL showed a higher risk of AS than those with serum phosphorus levels measuring

Summary: Galactose (Gal)-deficient IgA1 (Gd-IgA1) is involved in IgA nephropathy (IgAN) pathogenesis. To reflect racial differences in clinical characteristics, we assessed disease- and race-specific heterogeneity in the O-glycosylation of the IgA1 hinge region (HR). We determined serum Gd-IgA1 levels in Caucasians (healthy controls [HCs], n = 31; IgAN patients, n = 63) and Asians (HCs, n = 20; IgAN patients, n = 60) and analyzed profiles of serum IgA1 HR O-glycoforms. Elevated serum Gd-IgA1 levels and reduced number of Gal residues per HR were observed in Caucasians. Reduced number of N-acetylgalactosamine (GalNAc) residues per HR and elevated relative abundance of IgA1 with three HR O-glycans were common features in IgAN patients; these features were associated with elevated blood pressure and reduced renal function. We speculate that the mechanisms underlying the reduced GalNAc content in IgA1 HR may be relevant to IgAN pathogenesis.

Abstract Background Patients with chronic kidney disease often experience metabolic acidosis. Whether oral sodium bicarbonate can reduce mortality in patients with metabolic acidosis has been debated for years. Hence, this study was conducted to evaluate the utility of sodium bicarbonate in patients who will undergo dialysis therapy. In this study, we investigated the effect of oral sodium bicarbonate therapy on mortality in patients with end-stage kidney disease (ESKD) initiated on dialysis therapy. Methods We conducted an observational study of patients when they started dialysis therapy. There were 17 centres participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis. Data were available on patients’ sex, age, use of sodium bicarbonate, drug history, medical history, vital data, and laboratory data. We investigated whether patients on oral sodium bicarbonate for more than three months before dialysis initiation had a better prognosis than those without sodium bicarbonate therapy. The primary outcome was defined as all-cause mortality. Results The study included 1524 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 1030 were men and 492 women, with a mean age of 67.5 ± 13.1 years. Of these, 677 used sodium bicarbonate and 845 did not; 13.6% of the patients in the former group and 21.2% of those in the latter group died by March 2015 (p

Objectives: Vascular calcification is common in patients with advanced chronic kidney disease (CKD) and contributes to cardiovascular disease. Accumulating evidence indicates that CKD patients often acquire subclinical vitamin K deficiency, which is associated with vascular calcification. Methods: This prospective, randomized, parallel group, multicenter trial (UMINID000011490) will include 200 dialysis patients in an open-label, two-arm design. After baseline computed tomography of the abdominal aorta, patients will be randomized to two groups that will either (1) continue receiving standard care or (2) receive additional oral supplementation with menatetrenone (45 mg/day). The treatment duration will be 24 months, and the computed tomography scan will be repeated after 12 and 24 months. The primary endpoint is the progression of abdominal aortic calcification, which is calculated as absolute changes based on the Agatston score. The secondary endpoints are the decrease in bone mineral density (measured by dual-energy X-ray absorptiometry), the biomarkers associated with vitamin K, vitamin K intake (evaluated by the food frequency questionnaire), and the biomarkers associated with vascular calcification. Conclusions: This study aims to confirm whether vitamin K has inhibitory effects on calcification that can be clinically determined. Trial registration: UMINID000011490.

Abstract The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m2. The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.

Background The benefits of vitamin D receptor activators (VDRAs) for patients with chronic kidney disease are well recognized. However, the optimal criteria for patient selection, dosage forms, and duration providing the highest benefit and the least potential risk remain to be confirmed. Materials and methods The study population was derived from the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis, a multicenter prospective cohort study of 1520 incident dialysis patients. According to the VDRA usage status in March 2015 (interim report), the 967 patients surviving after March 2015 were classified into three groups: without VDRA (NV, n = 177), oral VDRA (OV, n = 447), and intravenous VDRA (IV, n = 343). Mortality rates were compared using the log-rank test, and factors contributing to all-cause mortality were examined using both univariate and multivariate Cox proportional hazard regression analyses. Results There were 104 deaths (NV, n = 27; OV, n = 53; IV, n = 24) during the follow-up period (1360 days, median), and significant differences in cumulative survival rates were observed between the three groups (p = 0.010). Moreover, lower all-cause mortality was associated with IV versus NV (hazard ratio, 0.46 [95% confidence interval 0.24–0.89]; p = 0.020). Conclusion This study demonstrated the impact of the VDRA dosage form on the short-term survival of incident hemodialysis patients during the introduction period. Our results suggest that relatively early initiation of intravenous VDRA in patients beginning hemodialysis may have some clinical potential.

Abstract Background The present study aimed to investigate associations between long-term renal function, whether IgG4-related tubulointerstitial nephritis (TIN) was diagnosed by renal biopsy at initial examination, chronic kidney disease (CKD) stage, and histological stage in patients with IgG4-related TIN. Methods This study used a retrospective cohort design including almost all patients who underwent renal biopsy at Fujita Health University Hospital and Nagoya University or its affiliated hospitals in Aichi between April 2003 and March 2015 (n = 6977 renal biopsies). The primary outcome was longitudinal changes in eGFR. Main exposures were whether IgG4-related TIN was diagnosed by renal biopsy at the initial examination, CKD stage, and its histological stage. Linear mixed models were performed to examine associations. Results Of the 6977 samples, there were 24 patients (with 201 records due to repeated measures) with IgG4-related TIN (20 men, mean age, 68.7 ± 9.7 years). They were followed up 6.6 ± 2.8 years after the renal biopsy and underwent glucocorticoid treatment. We found significant increase in eGFR from the baseline to 2 and 6 months after treatment initiation, which was maintained until 60 months. Patients initially diagnosed with IgG4-related TIN had higher eGFR from the baseline (at the start of treatment) to 60 months than those who were not. Compared with patients with CKD stage 3, patients with CKD stages 4 and 5 had lower eGFR at the baseline and other time points. Patients with histological stage B had comparatively lower eGFR at each point than stage A patients. Those mean differences of eGFR were stable from the baseline to 60 months. Conclusions After the treatment initiation, renal function rapidly improved and maintained for a long period, even with advanced CKD stage. We showed importance of early diagnosis of IgG4-related TIN in maintaining eGFR.

Abstract Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

Introduction There are few studies on the association between serum uric acid (UA) level and mortality in incident dialysis patients. We aimed to clarify whether the serum UA level at dialysis initiation is associated with mortality during maintenance dialysis. Methods We enrolled 1486 incident dialysis patients who participated in a previous multicenter prospective cohort study in Japan. We classified the patients into the following five groups according to their serum UA levels at dialysis initiation: G1 with a serum UA level

IntroductionDegenerative aortic valve stenosis (AS) is a chronic progressive disease that resembles atherosclerosis development. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is reportedly associated with accelerated atherosclerosis. This study aimed to examine the development of AS in patients with myeloperoxidase-AAV (MPO-AAV) with renal involvement at more than 1 year after the onset of vasculitis.MethodsWe performed a retrospective review of clinical records of MPO-AAV patients with renal involvement without AS at the onset of vasculitis who were treated in three hospitals and three dialysis clinics.ResultsThe study included 97 MPO-AAV patients with renal involvement and 230 control patients with chronic kidney disease (CKD). Among them, 64 patients had AS. The prevalence rates of AS were 28.9% and 15.7% in MPO-AAV and control patients, respectively (p = 0.006). The multivariable logistic regression analysis showed that MPO-AAV, dialysis dependence, and hypertension were independently associated factors for AS. In MPO-AAV patients, systolic blood pressure was positively significantly associated with AS, whereas glucocorticoid dose of induction therapy was negatively significantly associated. The use of cyclophosphamide tended to be negatively associated with AS. The survival rate was significantly lower for patients with AS than for those without AS.ConclusionsThe AS prevalence rate was significantly higher in MPO-AAV patients at more than 1 year after the onset of vasculitis than in control CKD patients. Therefore, regular monitoring of echocardiography during MPO-AAV treatment is suggested.

Objectives Patients with peripheral artery disease (PAD) are reported to have a poorer prognosis than those without PAD. PAD is sometimes found at dialysis initiation, but its influence on the prognosis in these patients has not been investigated. We aimed to compare the mortality rate between patients with PAD at the time of dialysis initiation and those without PAD.Design We undertook an observational prospective multicenter study of patients starting dialysis treatment. Data were collected on patients’ sex, age, presence of PAD, medication, medical history and clinical and laboratory data.Setting Seventeen centers participated in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis.Participants A total of 1524 patients with chronic kidney disease started dialysis from October 2011 to September 2013. The patients were followed-up until March 2015. During this time, there were two patients who lost the follow-up.Primary and secondary outcome measures The primary outcome was defined as all-cause mortality. The secondary outcomes were defined as each cause of mortality.Results This study included 1030 men and 492 women with a mean age of 67.50±13.10 years. Of these, 71 had PAD and 1451 did not have PAD. After a median follow-up of 814.5 days, 33.80% of the former group and 17.00% of the latter group had died in March 2015 (p=0.001). After adjusting for confounding factors, PAD at dialysis initiation remained an independent risk factor for mortality (p

With the global problem of aging, it has become more difficult to improve the prognosis of older dialysis patients. Extended-hours hemodialysis offers longer treatment time compared to conventional hemodialysis regimen and provides favorable metabolic status, hemodynamic stability, and increased dietary intake. Despite prior studies reporting that in-center extended-hours hemodialysis can reduce the mortality rate, the treatment impact on elderly patients remains unclear. Therefore, we examined the association between extended-hours hemodialysis compared to conventional hemodialysis and all-cause mortality. Survival analyses using Cox proportional hazard model with multivariable adjustments and propensity-score based method were performed to compare mortality risk between 198 consecutive patients who started in-center extended-hours hemodialysis (Extended-HD) and 1407 consecutive patients who initiated conventional hemodialysis. The median age was 67.1 years in the Extended-HD group and 70.7 years in the conventional hemodialysis group. Extended-HD was associated with lower all-cause mortality in overall patients and the subgroup >70 years (adjusted hazard ratios of 0.60 [95% CI, 0.39-0.91] and 0.35 [95% CI, 0.18-0.69], respectively). There was a significant interaction between age >70 years and Extended-HD. In conclusion, extended-hours hemodialysis was associated with a lower mortality rate, especially in elderly patients.

Artificial intelligence is increasingly being adopted in medical fields to predict various outcomes. In particular, chronic kidney disease (CKD) is problematic because it often progresses to end-stage kidney disease. However, the trajectories of kidney function depend on individual patients. In this study, we propose a machine learning-based model to predict the rapid decline in kidney function among CKD patients by using a big hospital database constructed from the information of 118,584 patients derived from the electronic medical records system. The database included the estimated glomerular filtration rate (eGFR) of each patient, recorded at least twice over a period of 90 days. The data of 19,894 patients (16.8%) were observed to satisfy the CKD criteria. We characterized the rapid decline of kidney function by a decline of 30% or more in the eGFR within a period of two years and classified the available patients into two groups-those exhibiting rapid eGFR decline and those exhibiting non-rapid eGFR decline. Following this, we constructed predictive models based on two machine learning algorithms. Longitudinal laboratory data including urine protein, blood pressure, and hemoglobin were used as covariates. We used longitudinal statistics with a baseline corresponding to 90-, 180-, and 360-day windows prior to the baseline point. The longitudinal statistics included the exponentially smoothed average (ESA), where the weight was defined to be 0.9*(t/b), where t denotes the number of days prior to the baseline point and b denotes the decay parameter. In this study, b was taken to be 7 (7-day ESA). We used logistic regression (LR) and random forest (RF) algorithms based on Python code with scikit-learn library (https://scikit-learn.org/) for model creation. The areas under the curve for LR and RF were 0.71 and 0.73, respectively. The 7-day ESA of urine protein ranked within the first two places in terms of importance according to both models. Further, other features related to urine protein were likely to rank higher than the rest. The LR and RF models revealed that the degree of urine protein, especially if it exhibited an increasing tendency, served as a prominent risk factor associated with rapid eGFR decline.

Introduction: As glomerular filtration rate (GFR) decreases, serum phosphate level increases. Previous reports indicated that serum phosphate level was associated with mortality in patients on dialysis. However, few reports have examined the association using dialysis initiation as the baseline period. Methods: This was a multicenter prospective cohort analysis including 1492 patients. Patients were classified into four quartiles based on the serum phosphate level at dialysis initiation, with Q1 being the lowest and Q4 the highest. All-cause mortality after dialysis initiation was compared using the log-rank test. The propensity score represented the probability of being assigned to group Q1 or Q2–4. All-cause mortality was compared in propensity score-matched patients by using the log-rank test for Kaplan–Meier curves. All-cause mortality of Q1 was compared with that for Q2–4 using multivariate Cox proportional hazard regression analysis. All-cause mortality was also determined among stratified groups with or without use of phosphate binders. Results: Significant differences in cumulative survival rates were observed between the four groups (p

IgA1 with galactose (Gal)-deficient hinge-region (HR) O-glycans (Gd-IgA1) plays a key role in IgA nephropathy (IgAN), and the serum level of Gd-IgA1 is elevated in the majority of IgAN patients. To characterize the involvement of IgA1 in the development and progression of IgAN, O-glycan micro-heterogeneity and attachment sites need to be analyzed, as each HR has nine potential sites for O-glycosylation. We have developed an on-line liquid chromatography (LC) hybrid quadrupole mass filter/linear ion trap/orbitrap mass spectrometry (MS) protocol, which was used to analyze IgA1 from a patient with IgAN. LC-MS profiling provided the overall O-glycan micro-heterogeneity distribution of IgA1 HR O-glycoforms. The LC-extracted ion chromatogram (XIC) of HR O-glycoforms containing Gal-deficient O-glycans indicated that the Gal-deficient O-glycans attached at specific sites. Structural isomers based on changes in the amino acid position of the attached glycans were identified in relation to the IgA1 HR O-glycoforms containing Gal-deficient O-glycans. To identify the predominant O-glycoforms in the serum IgA1 from IgAN patients as candidate biomarkers, O-glycan micro-heterogeneity and attachment sites, including isomeric structures, need to be analyzed. Our MS-based approach is useful in this respect and should prove a valuable tool for the development of biomarkers for IgA1 HR O-glycosylation in IgAN.

Abstract Background Aortic stenosis (AS) is common in patients on dialysis as well as in the general population. AS leads to difficulty with dialysis therapy because of unstable conditions such as intradialytic hypotension due to low cardiac output. However, the precise morbidity rates and risk factors of AS in patients on dialysis are unknown. Moreover, there are no large-scale observational studies regarding the association between AS in patients on dialysis and mortality. Therefore, we will investigate whether morbidity of AS in patients on dialysis is associated with mortality. Methods This is a multicenter prospective cohort analysis in the Tokai region of Japan. The 75 participating centers in this study will enroll approximately 2400 patients during 12 months, with or without AS. We started enrollment in July 2017 and will follow patents until June 2023. Transthoracic echocardiography will be performed to evaluate aortic valve. Parameters used for evaluation of aortic valve are mean pressure gradient between left ventricle and ascending aorta, aortic valve area, and maximum aortic jet velocity. We will diagnose AS using the criteria based on the 2014 American Heart Association/ American College of Cardiology Guideline. We will also perform transthoracic echocardiography at 12, 24, 36, 48, and 60 months. Survival prognosis and CV events will be determined at the end of June 2019, 2020, 2021, 2022, and 2023. Development of AS will be also evaluated as new onset or annual change in AS parameters. We will classify patients based on the presence or absence of AS and the stages of AS and will compare outcomes. Study outcomes will include the following: 1) all-cause mortality rates; 2) incidence of cardiovascular (CV) events; 3) CV-related mortality rates; 4) infection-related mortality rates; 5) new onset or development of AS. Discussion We will consider the following hypotheses in this study, among others: The prevalence of AS is higher in dialysis patients; new onset and development of AS are associated with factors that are specific for dialysis, such as hyperphosphatemia, hyperparathyroidism, and medication; and outcomes in AS patients are poorer than in patients without AS at baseline. Trial registration UMIN000026756, Registered March 29 2017.

Abstract Background Patients with late referral and positive history of volume overload may have a poor prognosis after initiating dialysis due to insufficient and/or inadequate management of complications of renal failure and the lack of better dialysis preparation. Little is known about the influence of the relationship between history of volume overload and late referral on prognosis. Methods We analyzed 1475 patients who had initiated dialysis for the first time from October 2011 to September 2013. late referral was defined as referral to a nephrologist

Abstract Background The Geriatric Nutritional Risk Index (GNRI) is a nutritional screening method primarily developed for elderly people; it is also reported to be useful for predicting mortality in patients on maintenance dialysis. However, it is unclear whether it is useful at the time of dialysis initiation, which is accompanied by large weight fluctuations and unstable nutritional status. Methods The study included 1524 patients with chronic kidney disease who commenced dialysis therapy at 17 centers. Patients commenced dialysis between October 2011 and September 2013 and were followed up until March 2015. Results We analyzed 1489 patients whose GNRI could be calculated and whose prognosis was clear. The mean GNRI was 87.60 (median 87.86). We divided patients based on the median value into a high (H) and low (L) group. The H group included 728 patients (mean GNRI 95.2 ± 4.9, mean age 65.8 ± 13.2 years, 69.3% men), and the L group included 761 patients (mean GNRI 80.3 ± 6.1, mean age 69.1 ± 12.8 years, 66.0% men). Mortality was significantly higher in the L group (L, 22.2% vs. H, 12.6%, P

Abstract Background Sepsis is a systemic inflammatory response syndrome caused by infectious disease. Severe sepsis and septic shock are extremely serious conditions with poor prognoses. It is reported that cytokines are deeply involved in the disease mechanism. Continuous hemodiafiltration (CHDF) using a poly(methyl methacrylate) (PMMA) membrane is reported to adsorb various cytokines and improve the status of patients with sepsis. Recently, another cytokine-adsorbing hemofilter, acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane, has become available for CHDF in patients with sepsis. However, the clinical efficacy of this membrane remains unclear. Therefore, in this study, we compared the efficacy of AN69ST and PMMA membranes. Methods This retrospective study included patients with severe sepsis or septic shock who underwent CHDF for at least 24 h in the intensive care unit from January 2013 to August 2016. Results This study included 49 patients who underwent CHDF, 32 using an AN69ST membrane and 17 using a PMMA membrane. In the AN69ST and PMMA groups, average age was 71.1 ± 11.4 years and 74.7 ± 9.4 years, respectively, and percentage of men was 71.9 and 88.2%, respectively. Severity of sepsis and vital signs were not significantly different between groups at the start of CHDF. In addition, 28-day mortality was not significantly different between groups (43.8 vs. 35.3%, P = 0.1625). However, heart rate in the AN69ST group decreased significantly early in the course of CHDF (6, 12, and 24 h, P

Some variables including age, comorbidity of diabetes, and so on at dialysis initiation are associated with patient prognosis. Cardiovascular (CV) events are a major cause of death, and adequate models that predict prognosis in dialysis patients are warranted. Therefore, we created models using some variables at dialysis initiation. We used a database of 1,520 consecutive dialysis patients (median age, 70 years; 492 women [32.4%]) from a multicenter prospective cohort study. We established the primary endpoint as a composite of the incidence of first CV events or all-cause death. A multivariable Cox proportional hazard regression model was used to construct a model. We considered a complex and a simple model. We used area under the receiver operating characteristic curve (AUROC) to assess and compare the predictive performances of the prediction models and evaluated the improvement in discrimination using the complex model versus the simple model using net reclassification improvement (NRI). We then assessed integrated discrimination improvement (IDI) to evaluate improvements in average sensitivity and specificity. Of 392 deaths, 152 were CV-related. Totally, 506 CV events occurred during the follow-up period (median 1,285 days). Finally, 692 patients reached the primary endpoint. Baseline data were set at dialysis initiation. AUROC for the primary endpoint was 0.737 (95% confidence interval [CI], 0.712-0.761) in the simple model and 0.765 (95% CI, 0.741-0.788) in the complex model. There were significant intergroup differences in NRI (0.44; 95% CI, 0.34-0.53; p < 0.001) and IDI (0.02; 95% CI, 0.02-0.03; p < 0.001). We prepared a Shiny R application for each model to automatically calculate the predicted occurrence probability (https://statacademy.shinyapps.io/App_inaguma_20190717/). The complex model made more accurate predictions than the simple model. However, the intergroup difference was not significant. Hence, the simple model was more useful than the complex model. The tool was useful in a real-world clinical setting because it required only routinely available variables. Moreover, we emphasized that the tool could predict the incidence of CV events or all-cause mortality for individual patients. In the future, we must confirm its external validity in other prospective cohorts.

IntroductionProteinuria is a potent predictor of adverse events in general, although a few large studies have reported a J-shaped association between proteinuria and mortality in individuals with glomerular filtration rate MethodsAmong 1,380 Japanese patients who initiated dialysis, we quantified the association of pre-dialysis dipstick proteinuria (negative/trace, 1+, 2+, and ≥3+) with mortality using Cox models adjusting for potential confounders, such as age, gender, clinical history of hypertension, diabetes, and cardiovascular disease.ResultsMean age of study participants was 67.4 (SD 13.0) years, and 67.6% were men. The most common dipstick proteinuria category was ≥3+ (55.4%), followed by 2+ (31.2%), 1+ (9.9%), and negative or trace (3.5%). Patients with lower proteinuria level were older than those with higher proteinuria. Lower proteinuria was significantly associated with a higher risk of all-cause mortality, even after accounting for potential confounders (p for trend ConclusionsIn incident dialysis patients, pre-dialysis proteinuria was inversely associated with mortality risk. Although future studies are needed to identify mechanisms, our findings suggest the need to carefully interpret proteinuria in patients with incident dialysis.