Sex estimation from maxillofacial radiographs using a deep learning approach.

The purpose of this study was to construct deep learning models for more efficient and reliable sex estimation. Two deep learning models, VGG16 and DenseNet-121, were used in this retrospective study. In total, 600 lateral cephalograms were analyzed. A saliency map was generated by gradient-weighted class activation mapping for each output. The two deep learning models achieved high values in each performance metric according to accuracy, sensitivity (recall), precision, F1 score, and areas under the receiver operating characteristic curve. Both models showed substantial differences in the positions indicated in saliency maps for male and female images. The positions in saliency maps also differed between VGG16 and DenseNet-121, regardless of sex. This analysis of our proposed system suggested that sex estimation from lateral cephalograms can be achieved with high accuracy using deep learning.

Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients with Non-Dialysis-Dependent Chronic Kidney Disease (RADIANCE-CKD Study).

INTRODUCTION: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. We hypothesized that the prediction of ESA resistance during ESA administration would be very useful in deciding on a treatment plan. METHODS: Patients enrolled in a randomized controlled trial to evaluate renal prognosis in anemic patients with non-dialysis-dependent chronic kidney disease with hyporesponsiveness to ESA were included; the patients had different target hemoglobin levels. A landmark analysis was performed at 3 months into the study. To construct a predictive model for the severe ESA hypo-responder group, in which there was no increase in hemoglobin even with active treatment, background factors and serum test items that affect anemia at study entry were included in a logistic regression model, the area under the curve (AUC) and 95% confidence intervals (CI) were estimated, and sensitivity and specificity were calculated. This study was a post hoc sub-analysis of a randomized controlled trial. RESULTS: The AUC for the 19 existing risk factors as predictors was 0.783 (95% CI: 0.711-0.855). Among the 19 risk factors, the combination of six factors (hemoglobin level, systolic blood pressure, weight, gender, smoking status, and hypertensive retinopathy) with the largest χ2 statistics were selected by multiple logistics regression. The AUC for these 6 predictors was 0.716 (95% CI: 0.634-0.799). To the six existing risk factors, five serum test items that affect anemia (vitamin B12, vitamin B6, folic acid, parathyroid hormone, and 25-hydroxyvitamin D) were added, for a total of 11 risk factors, with a similar AUC of 0.736 (95% CI: 0.655-0.817), sufficient to predict ESA resistance. CONCLUSIONS: Our results suggest that existing risk factors and serum test items can be used to predict ESA resistance in patients with non-dialysis-dependent chronic kidney disease on ESA.

Randomized, double-blind, placebo-controlled phase 3 study of bardoxolone methyl in patients with diabetic kidney disease: design and baseline characteristics of the AYAME study.

BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD), but currently available treatments do not improve kidney function or prevent the initiation of dialysis/kidney replacement therapy. A previous study demonstrated that bardoxolone methyl improves the estimated glomerular filtration rate (eGFR), but the study was prematurely terminated because of an imbalance in heart failure between treatment groups. The subsequent phase 2 TSUBAKI study demonstrated no incidence of heart failure and an improved eGFR and GFR as determined by inulin clearance in DKD patients. METHODS: This randomized, double-blind, placebo-controlled multicentre phase 3 study was designed to assess the efficacy and safety of bardoxolone methyl in DKD patients with an eGFR ≥15.0-<60.0 ml/min/1.73 m2 and a urinary albumin:creatinine ratio (UACR) ≤3500 mg/g but without risk factors for heart failure. The primary endpoint is the time to onset of a ≥30% decrease in the eGFR or ESKD. Randomized patients (1:1) have been under treatment with once-daily oral bardoxolone methyl (5, 10 or 15 mg by intrapatient dose adjustment) or placebo for at least 3 years. RESULTS: The mean age of the 1013 patients is 65.9 years, 21.5% are female, the mean eGFR is 37.84 ml/min/1.73 m2 and the median UACR is 351.80 mg/g. CONCLUSIONS: Appropriate patients are enrolled in this study. This study will investigate the long-term efficacy and safety of bardoxolone methyl in DKD patients covering a wider range of eGFR (≥15.0-<60.0 ml/min/1.73 m2) and albuminuria (≤3500 mg/g) compared with previous studies.

Hyporesponsiveness to erythropoiesis-stimulating agent in non-dialysis-dependent CKD patients: The BRIGHTEN study.

Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.

Renal prognoses by different target hemoglobin levels achieved by epoetin beta pegol dosing to chronic kidney disease patients with hyporesponsive anemia to erythropoiesis-stimulating agent: a multicenter open-label randomized controlled study.

BACKGROUND: There is no evidence regarding appropriate target hemoglobin levels in chronic kidney disease (CKD) patients with an erythropoiesis-stimulating agent (ESA)-hyporesponsiveness. Therefore, we conducted a randomized controlled study in non-dialysis dependent CKD (NDD-CKD) patients with ESA-hyporesponsiveness, comparing results of intensive versus conservative treatment to maintain hemoglobin levels. METHODS: This was a multicenter, open-label, randomized, parallel-group study conducted at 89 institutions. Among NDD-CKD patients, those with ESA-hyporesponsive renal anemia were randomly assigned to an intensive treatment group, to which epoetin beta pegol was administered with target hemoglobin level of 11 g/dL or higher, or conservative treatment group, in which the hemoglobin levels at enrollment (within ± 1 g/dL) were maintained. The primary endpoint was the time to the first kidney composite event defined as (1) transition to renal replacement therapy (dialysis or renal transplantation); (2) reduction of estimated glomerular filtration rate (eGFR) to less than 6.0 mL/min/1.73 m2; or (3) reduction of eGFR by 30% or more. Secondary endpoints were kidney function (change rate in eGFR), cardiovascular (CV) events, and safety. RESULTS: Between August 2012 and December 2015, 385 patients were registered, and 362 patients who met the eligibility criteria were enrolled. There was no significant difference in kidney survival or in CV events between the two groups. However, the incidences of the 3 types of kidney composite events tended to differ. CONCLUSIONS: In NDD-CKD patients with ESA-hyporesponsive renal anemia, the aggressive administration of ESA did not clearly extend kidney survival or result in a significant difference in the incidence of CV events.

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan.

BACKGROUND: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN. METHODS: Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed. RESULTS: The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 µg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). CONCLUSIONS: Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.

Low transferrin saturation (TSAT) and high ferritin levels are significant predictors for cerebrovascular and cardiovascular disease and death in maintenance hemodialysis patients.

Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (≥100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low ß2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term.

Randomized Clinical Trial on the Effect of Bardoxolone Methyl on GFR in Diabetic Kidney Disease Patients (TSUBAKI Study).

INTRODUCTION: Bardoxolone methyl significantly increases estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD). However, the phase 3 study, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: the Occurrence of Renal Events (BEACON), was terminated prematurely because bardoxolone methyl increased the risk for early-onset fluid overload in patients with identifiable risk factors for heart failure (elevated baseline B-type natriuretic peptide levels >200 pg/ml and prior history of hospitalization for heart failure). The Phase 2 Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) study aimed to determine if patients without risk factors can mitigate the risk for fluid overload and whether changes in eGFR with bardoxolone methyl reflect true increases in GFR. METHODS: This phase 2, randomized, multicenter, double-blind, placebo-controlled study enrolled patients with type 2 diabetes and stage 3-4 CKD. Patients were randomized 1:1 to bardoxolone methyl (n = 41) or placebo (n = 41) (cohort G3), or 2:1 to bardoxolone methyl (n = 24) or placebo (n = 14) (cohort G4), administered orally once daily for 16 weeks using a dose-titration scheme. The primary efficacy endpoint was change from baseline in GFR measured by inulin clearance at week 16 in the cohort G3. RESULTS: A total of 40 patients were evaluated for the prespecified primary efficacy analysis. Mean change (95% confidence interval [CI]) from baseline in GFR was 5.95 (2.29 to 9.60) and -0.69 (-3.83 to 2.45) ml/min per 1.73 m2 for patients randomized to bardoxolone methyl and placebo, respectively, with a significant intergroup difference of 6.64 ml/min per 1.73 m2 (P = 0.008). Increases in the albumin/creatinine ratio were observed in the bardoxolone methyl group vs the placebo group. The most common adverse events (≥15% in either group) were viral upper respiratory tract infection, increased alanine aminotransferase, increased aspartate aminotransferase, increased γ-glutamyltransferase, and constipation. Peripheral edema was reported by 4 patients receiving bardoxolone methyl and by 1 patient receiving placebo; all events were mild and self-limiting. No patient died or experienced heart failure. The study discontinuation rate was higher in the bardoxolone methyl group (cohort G3, n = 8; cohort G4, n = 7) than the placebo group (cohort G3, n = 1; cohort G4, n = 0). CONCLUSION: Bardoxolone methyl significantly increased measured GFR, and further investigation is ongoing to evaluate whether it provides clinical benefit without major safety concerns in selected patients with CKD.

Risk stratification based on J-ACCESS risk models with myocardial perfusion imaging: Risk versus outcomes of patients with chronic kidney disease.

BACKGROUND: This study aimed to validate the accuracy of major-event risk models created in the multicenter J-ACCESS prognostic study in a new cohort of patients with chronic kidney disease (CKD). METHODS AND RESULTS: Three multivariable J-ACCESS risk models were created to predict major cardiac events (cardiac death, non-fatal acute coronary syndrome, and severe heart failure requiring hospitalization): Model 1, four variables of age, summed stress score, left ventricular ejection fraction and diabetes; Model 2 with five variables including estimated glomerular filtration rate (eGFR, continuous); and Model 3 with categorical eGFR. The validation data used three-year (3y) cohort of patients with CKD (n = 526, major events 11.2%). Survival analysis of low (< 3%/3y), intermediate (3% to 9%/3y), and high (> 9%/3y)-risk groups showed good stratification by all three models (actual event rates: 3.1%, 9.9%, and 15.9% in the three groups with eGFR ≥ 15 mL/min/1.73 m2, P = .0087 (Model 2). However, actual event rates were equally high across all risk groups of patients with eGFR < 15 mL/min/1.73 m2. CONCLUSION: The J-ACCESS risk models can stratify patients with CKD and eGFR ≥ 15 mL/min/1.73 m2, but patients with eGFR < 15 mL/min/1.73 m2 are potentially at high risk regardless of estimated risk values.

Resistance to Erythropoiesis-Stimulating Agents in Pre-Dialysis and Post-Dialysis Mortality in Japanese Incident Hemodialysis Patients.

BACKGROUND/AIMS: There is lack of definitive evidence about the association between erythropoiesis-stimulating agent (ESA) responsiveness in the pre-dialysis phase and mortality. Therefore, we conducted a hospital-based, retrospective, cohort study to assess the predictive value of ESA response for prognosis in incident hemodialysis patients. METHODS: A total of 108 patients without preexisting cardiovascular disease who had been started on maintenance hemodialysis were studied. ESA responsiveness just before starting dialysis was estimated using an erythropoietin resistance index (ERI). The endpoint was defined as all-cause death. RESULTS: During a mean follow-up period of 3.1 ± 1.6 years, 18 (17%) patients died. Overall, the multivariate Cox regression analysis revealed that the log-transformed ERI remained an independent predictor of all-cause death after adjustment using a propensity score (hazard ratio 2.25, 95% CI 1.25-4.06). CONCLUSIONS: Among incident hemodialysis patients, hyporesponsiveness to ESA may be associated with mortality.

Prognostic study of cardiac events in Japanese patients with chronic kidney disease using ECG-gated myocardial Perfusion imaging: Final 3-year report of the J-ACCESS 3 study.

BACKGROUND: Myocardial perfusion imaging (MPI) is considered useful for risk stratification among patients with chronic kidney disease (CKD), without renal deterioration by contrast media. METHODS AND RESULTS: The Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS 3) is a multicenter, prospective cohort study investigating the ability of MPI to predict cardiac events in 529 CKD patients without a definitive coronary artery disease. All patients were assessed by stress and rest MPI with 99mTc-tetrofosmin and data were analyzed using a defect scoring method and QGS software. Major cardiac events were analyzed for 3 years after registration. The mean eGFR was 29.0 ± 12.8 (mL/minute/1.73 m2). The mean summed stress/rest/difference (SSS, SRS, SDS) scores were 1.9 ± 3.8, 1.1 ± 3.0, and 0.8 ± 1.8, respectively. A total of 60 cardiac events (three cardiac deaths, six sudden deaths, five nonfatal myocardial infarctions, 46 hospitalization cases for heart failure) occurred. The event-free survival rate was lower among patients with kidney dysfunction, higher SSS, and higher CRP values. Multivariate Cox regression analysis independently associated SSS ≥8, eGFR <15 (mL/minute/1.73 m2), and CRP ≥0.3 (mg/dL) with cardiac events. CONCLUSIONS: Together with eGFR and CRP, MPI can predict cardiac events in patients with CKD.

Association of Circulatory Iron Deficiency With an Enlarged Heart in Patients With End-Stage Kidney Disease.

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.

Biological variation of procalcitonin levels in hemodialysis patients.

BACKGROUND: There is no obvious evidence regarding biological variation of procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The aim of this study was to determine the within- and between-person biological variation of PCT levels in HD patients without infections. METHODS: A multicenter, prospective, cohort study enrolled 123 HD patients without any signs of infectious disease. Baseline PCT levels were determined pre- and post-HD, and then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and 24 weeks after baseline blood-sampling, regardless of the presence or absence of infectious disease. Analytical variation (CVa), the within-person biological variation (CVi), between-person biological variation (CVb), individual index (II), and the reference change value (RCV) were calculated. RESULTS: The mean age was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD was 87 months. The median value for baseline pre-HD PCT was 0.23 ng/mL, which is much higher than the reference level for healthy individuals. PCT levels decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II was 0.46, and RCV was calculated as 96.4% with 99% probability. CONCLUSIONS: The PCT level was significantly higher in stable HD patients without manifest bacterial infection. CVb was more variable than CVi in HD patients, which indicates that relative change is more important than absolute PCT levels for diagnosing bacterial infection, and doubling or more of the baseline PCT level may imply the presence of a bacterial infection in HD patients.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Dry weight targeting: The art and science of conventional hemodialysis.

Fluid volume overload is common and is associated with adverse outcomes in hemodialysis patients. Practicing physicians individually manage fluid volume balance in their dialysis patients according to blood pressure, interdialytic weight gain, cardiac function, nutritional status, and other comorbidities. However, accurate assessment of fluid volume status remains a concern. Indicators of dry weight target have been explored further with newer concepts and technologies. In general, total body water comprises approximately 50%-60% of adult body weight (range, 45%-75%), and water comprises 73.3% of lean body mass. The standard hydration status between intracellular water and extracellular water is maintained at a ratio of 62:38 in healthy adults, which, however, is influenced universally by body cell volume driven by age and muscle mass. Fluid volume imbalance in dialysis patients also is characterized primarily by decreased body cell mass associated with aging and muscle attenuation, as well as excess extracellular water content associated with sodium retention, which may be associated with the reserve capacity for volume overload. Indeed, dialysis patients with a leaner body mass have a higher prevalence of hypertension, poorer hypertension control, and greater left ventricular hypertrophy. Understanding of these body composition changes by aging and sarcopenia can aid clinical decision making in the dry weight assessments in dialysis patients. Advising patients with consistently high interdialytic weight gain to practice salt restriction and providing appropriate nutritional support for malnourished patients with downward trajectory in their dry weight would be of great help to achieve optimal fluid volume status.

Rationale and design of oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN Trial).

BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.

Thallium-201 washout rate of stress myocardial perfusion imaging as a predictor of mortality in diabetic kidney disease patients initiating hemodialysis: an observational, follow-up study.

BACKGROUND: Thallium-201 washout rate of stress myocardial perfusion imaging (MPI) has been reported to correlate with coronary flow reserve which is a parameter of myocardial microcirculation. However, the evidence for its use in diabetic kidney disease (DKD) has been lacking, and the association between thallium-201 washout rate and adverse outcomes including death is unknown. Therefore, the present study was conducted to evaluate the predictive ability of thallium-201 washout rate for mortality in DKD patients initiating hemodialysis. METHODS: A total of 96 patients with type 2 diabetes who had been started on maintenance hemodialysis undergoing stress MPI with thallium-201 within 1 year, 72 men and 24 women, with a median age of 67 years, were studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: During the mean follow-up period of 3.4 ± 2.1 years, 18 (18.8%) deaths occurred. Cumulative survival rates during the follow-up period, with thallium-201 washout rate levels in the lowest tertile (3.1-36.2%), the middle tertile (36.5-46.3%), and the highest tertile (46.4-66.2%), were 51.0, 86.5, and 85.3%, respectively. Overall, the multivariate Cox regression analysis revealed that thallium-201 washout rate remained an independent predictor of death after adjusting by confounding variables (HR 0.91, 95% CI 0.85-0.97). CONCLUSIONS: Among DKD patients initiating hemodialysis, thallium-201 washout rate seems to be useful for predicting death.

Point of care assessment of cardiac troponin T level in CKD patients with chest symptom.

We challenged to identify the cutoff value of cTnT in chronic kidney disease (CKD) patients by point of care assessment way. A single center, prospective cross-sectional study was planned and performed. 201 consecutive patients who were visited emergency room for chest symptoms were enrolled in this study. All patients were performed routine practice for differential diagnosis of chest symptom by cardiologist. Simultaneously, semiquantitative measurement of cTnT was performed using same blood sampling on the blind condition to cardiologists for this study. Study patients were divided into four groups according to the estimated glomerular filtration rate (eGFR), CKD1-2, CKD3, CKD4-5, and CKD5D. Usefulness of semiquantitative measurement for diagnosing ACEs was investigated in each group. 77 (38%) of total patient was diagnosed as acute coronary events (ACEs). About 50% of patients were showing cTnT level less than 0.03 ng/mL. The cTnT level over 0.1 ng/mL was found in 30% of total subjects. Mean quantitative value of cTnT was 0.29 ± 0.57 ng/mL in total subjects. Estimated cutoff value in CKD3 patients was 0.088 ng/mL with a sensitivity of 59.3% and specificity of 80.0%. Interestingly, the cutoff values of CKD1-2, CKD4-5, and CKD5D were 0.047, 0.18, and 0.27 respectively, which are half, two times, and three times of CKD3 cutoff value 0.088. The specificities of four cutoff values in each CKD group were showing over 80%, which is higher than sensitivity, respectively. In CKD patients, semiquantitative, point of care assessment of cTnT could be a useful tool for screening for ACEs.