Publications by authors named "Eiichiro Kanda"

92 Publications

High-performance dialyzers and mortality in maintenance hemodialysis patients.

Sci Rep 2021 Jun 10;11(1):12272. Epub 2021 Jun 10.

The Committee of Renal Data Registry, The Japanese Society for Dialysis Therapy, Tokyo, Japan.

Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β-microglobulin clearance rates of < 10, < 30, < 50, < 70, and ≥ 70 mL/min, respectively. We investigated the relationship of the 5 dialyzer types with 1-year mortality. This nationwide cohort study used data collected at the end of 2008 and 2009 by the Japanese Society for Dialysis Therapy Renal Data Registry. We enrolled 203,008 patients on maintenance hemodialysis who underwent hemodialysis for at least 1 year and were managed with any of the 5 dialyzer types. To evaluate the association of dialyzer type with 1-year all-cause mortality, Cox proportional hazards models and propensity score-matched analyses were performed. After adjustment of the data with clinicodemographic factors, the type I, II, and III groups showed significantly higher hazard ratios (HRs) than the type IV dialyzers (reference). After adjustment for Kt/V and β-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.
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http://dx.doi.org/10.1038/s41598-021-91751-wDOI Listing
June 2021

Cardiovascular and Renal Outcomes Associated With Hyperkalemia in Chronic Kidney Disease: A Hospital-Based Cohort Study.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 19;5(2):274-285. Epub 2021 Jan 19.

Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca KK, Osaka, Japan.

Objective: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease.

Patients And Methods: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score-matched hyperkalemic patients and normokalemic controls.

Results: Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was -5.75 and -1.79 mL/min/1.73 m, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively.

Conclusion: Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105529PMC
April 2021

Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia.

PLoS One 2021 11;16(5):e0251554. Epub 2021 May 11.

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.

Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152). The primary outcome was defined as end-stage kidney disease (ESKD) or death and was examined over a 1-year observation period. Overall, the mean Zn level was 59.6 μg/dl and the median eGFR was 20.3 ml/min/1.73 m2. The incidence of the primary outcome was higher in the low-Zn group (p<0.001). Various Cox proportional hazards models adjusted for baseline characteristics showed higher risks of the primary outcome in the low-Zn group than in the high-Zn group. Competing risks analysis showed that low Zn levels were associated with ESKD but not with death. Moreover, in propensity score-matched analysis, the low-Zn group showed a higher risk of the primary outcome [adjusted hazard ratio 1.81 (95% confidence interval 1.02, 3.24)]. Furthermore, an interaction was observed between Zn and serum albumin levels (interaction p = 0.026). The results of this study indicate that zinc deficiency is a risk factor for CKD progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251554PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112700PMC
May 2021

Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study.

Clin Kidney J 2021 May 27;14(5):1436-1442. Epub 2020 Oct 27.

Division of Nephrology, Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Background: Beta-2 microglobulin (β2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves β2M removal, yet β2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum β2M, evaluated trends in β2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of β2M on mortality.

Methods: We studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998-2018 ( = 23 976), and analysis of β2M and mortality in centers routinely measuring β2M spanned 2011-18 ( = 5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression.

Results: Median β2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011-18 (P = 0.87). Highest β2M tertile patients (>2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55-3.76) to 0.23 (0.13-0.42) per 100 patient-years. Compared with the lowest β2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94-1.43) and 1.38 (1.13-1.69) for the middle and highest tertiles. Mortality risk increased monotonically with β2M modeled continuously, with no indication of a threshold.

Conclusions: DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum β2M remains positively associated with mortality, even in the current high-flux HD era.
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http://dx.doi.org/10.1093/ckj/sfaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087125PMC
May 2021

Methods and Nutritional Interventions to Improve the Nutritional Status of Dialysis Patients in JAPAN-A Narrative Review.

Nutrients 2021 Apr 21;13(5). Epub 2021 Apr 21.

Blood Purification Unit, Hamamatsu University Hospital, Hamamatsu, Shizuoka 431-3192, Japan.

Patients receiving dialysis therapy often have frailty, protein energy wasting, and sarcopenia. However, medical staff in Japan, except for registered dietitians, do not receive training in nutritional management at school or on the job. Moreover, registered dietitians work separately from patients and medical staff even inside a hospital, and there are many medical institutions that do not have registered dietitians. In such institutions, medical staff are required to manage patients' nutritional disorders without assistance from a specialist. Recent studies have shown that salt intake should not be restricted under conditions of low nutrition in frail subjects or those undergoing dialysis, and protein consumption should be targeted at 0.9 to 1.2 g/kg/day. The Japanese Society of Dialysis Therapy suggests that the Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) is a useful tool to screen for older patients with malnutrition.
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http://dx.doi.org/10.3390/nu13051390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142969PMC
April 2021

A novel automated immunoassay for serum NY-ESO-1 and XAGE1 antibodies in combinatory prediction of response to anti-programmed cell death-1 therapy in non-small-cell lung cancer.

Clin Chim Acta 2021 Apr 15;519:51-59. Epub 2021 Apr 15.

Immuno-Oncology, Kawasaki Medical School, Okayama 701-0192, Japan. Electronic address:

Background: Anti-programmed cell death-1 (PD-1) antibodies (Abs) are key drugs in non-small-cell lung cancer (NSCLC) treatment; however, clinical benefits with anti-PD-1 monotherapy are limited. We reported that serum Abs against cancer-testis antigens NY-ESO-1 and XAGE1 predicted clinical benefits. We aimed to develop a fully automated immunoassay system measuring NY-ESO-1/XAGE1 Abs.

Methods: Sera from 30 NSCLC patients before anti-PD-1 monotherapy were reacted with recombinant NY-ESO-1 protein- or synthetic XAGE1 peptide-coated magnetic beads. ALP-conjugated Ab and chemiluminescent substrate were added and luminescence measured. These procedures were automated using high sensitivity chemiluminescent enzyme immunoassay (HISCL™). NY-ESO-1/XAGE1 Ab stability was tested under various conditions. Response prediction accuracy was evaluated using area under receiver operating curve (AUROC).

Results: HISCL detected specific serum NY-ESO-1/XAGE1 Abs, which levels in ELISA and HISCL were highly correlated. The Ab levels in HISCL were stable at four temperatures, five freeze/thaw cycles, and long-term storage; the levels were not interfered by common blood components. The Ab levels in 15 NSCLC responders to anti-PD-1 monotherapy were significantly higher than those in non-responders and healthy donors. The AUROC was the highest (0.91; 95% CI, 0.78-1.0) in combinatory prediction with NY-ESO-1/XAGE1 Abs.

Conclusion: Our immunoassay system is useful to predict clinical benefits with NSCLC immune-checkpoint therapy.
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http://dx.doi.org/10.1016/j.cca.2021.04.008DOI Listing
April 2021

Pre-dialysis Hyponatremia and Change in Serum Sodium Concentration During a Dialysis Session Are Significant Predictors of Mortality in Patients Undergoing Hemodialysis.

Kidney Int Rep 2021 Feb 29;6(2):342-350. Epub 2020 Dec 29.

Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan.

Background: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease.

Methods: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models.

Results: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05-1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01-1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05-1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137-140 mEq/L) and the lowest ΔSNa (≤2 mEq/L).

Conclusions: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.
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http://dx.doi.org/10.1016/j.ekir.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879213PMC
February 2021

Association between anemia and mortality in hemodialysis patients is modified by the presence of diabetes.

J Nephrol 2021 Jun 8;34(3):781-790. Epub 2021 Feb 8.

Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.

Background: The prevalence and severity of anemia differ between diabetic and non-diabetic patients. We investigated whether the effect of hemoglobin (Hb) on patient outcome was affected by the presence or absence of diabetes among Japanese patients receiving chronic hemodialysis (HD).

Methods: We enrolled 149,308 patients from a nationwide dialysis registry in Japan at the end of 2012 (mean age, 67.6 ± 12.3 years; male, 61.7%; diabetes, 43.5%; median dialysis duration, 65 months) who underwent three HD sessions weekly. One-year all-cause and cardiovascular (CV) mortality were assessed using Cox regression analysis and competing-risks regression analysis. We used multiple imputation to deal with missing covariate data.

Results: Baseline Hb and serum ferritin levels were independently associated with all-cause and CV mortality. In non-diabetic patients, a significantly higher risk for all-cause mortality compared to the reference group (10 to 11 g/dL) was observed in patients with Hb < 8 g/dL (hazard ratio (HR): 1.266; 95% confidence interval (CI) 1.097-1.460) and 8 to  9 g/dL(HR: 1.153; 95% CI 1.030-1.290). On the other hand, diabetic HD patients in the same Hb category group did not have increased risk of all-cause mortality.

Conclusions: We found that non-diabetic HD patients had an increased risk of all-cause mortality if they had lower Hb levels, whereas the effect of Hb levels on mortality was attenuated in diabetic HD patients. These data suggest that the association between Hb levels and mortality rate could be different between diabetic and non-diabetic HD patients.
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http://dx.doi.org/10.1007/s40620-020-00879-xDOI Listing
June 2021

The combination of malnutrition-inflammation and functional status limitations is associated with mortality in hemodialysis patients.

Sci Rep 2021 Jan 15;11(1):1582. Epub 2021 Jan 15.

Arbor Research Collaborative for Health, Ann Arbor, MI, USA.

The identification of malnutrition-inflammation-complex (MIC) and functional status (FS) is key to improving patient experience on hemodialysis (HD). We investigate the association of MIC and FS combinations with mortality in HD patients. We analyzed data from 5630 HD patients from 9 countries in DOPPS phases 4-5 (2009-2015) with a median follow-up of 23 [IQR 11, 31] months. MIC was defined as serum albumin < 3.8 g/dL and serum C-reactive protein > 3 mg/L in Japan and > 10 mg/L elsewhere. FS score was defined as the sum of scores from the Katz Index of Independence in Activities of Daily Living and the Lawton-Brody Instrumental Activities of Daily Living Scale. We investigated the association between combinations of MIC (+/-) and FS (low [< 11]/high [≥ 11]) with death. Compared to the reference group (MIC-/high FS), the adjusted hazard ratios [HR (95% CI)] for all-cause mortality were 1.82 (1.49, 2.21) for MIC-/low FS, 1.57 (1.30, 1.89) for MIC+/high FS, and 3.44 (2.80, 4.23) for MIC+/low FS groups. Similar associations were observed with CVD-related and infection-related mortality. The combination of MIC and low FS is a strong predictor of mortality in HD patients. Identification of MIC and poor FS may direct interventions to lessen adverse clinical outcomes in the HD setting.
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http://dx.doi.org/10.1038/s41598-020-80716-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811014PMC
January 2021

Postoperative recurrence of chronic subdural hematoma is more frequent in patients with blood type A.

J Neurosurg 2021 Jan 1:1-5. Epub 2021 Jan 1.

Departments of1Neurosurgery and.

Objective: Because of an aging society, the incidence of chronic subdural hematoma (CSDH) is increasing. This lesion is treated with simple burr hole irrigation, but one of the major issues is that CSDH frequently recurs. ABO blood type may be associated with a bleeding tendency and inflammation. However, its association with the recurrence of CSDH remains unknown. Therefore, the authors of the present study aimed to retrospectively investigate the association between ABO blood type and CSDH recurrence.

Methods: The authors retrospectively analyzed symptomatic CSDHs in 425 cerebral hemispheres of 376 patients who had undergone surgical treatment with irrigation of the hematoma via burr holes at their institution from January 2011 to September 2019. Among these were 366 CSDHs in 320 patients whose ABO blood type had been determined and who were included in this study.

Results: In the study, 307 patients with CSDHs in 350 hemispheres were followed up postoperatively until the disappearance of the CDSH or for at least 3 months. Recurrence of CSDH was observed in 37 patients (10.6%) after surgical treatment. Blood type A was found to be significantly associated with CSDH recurrence compared to non-A blood types: 24 of 153 CDSHs (15.7%) versus 13 of 197 CDSHs (6.6%) (p = 0.008). In the multivariable regression analysis, blood type A, in addition to thrombocytopenia, was a significant independent predictor of the recurrence of CSDH.

Conclusions: The study results showed that blood type A is an independent risk factor for the postoperative recurrence of CSDH and that careful follow-up in these patients may be needed.
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http://dx.doi.org/10.3171/2020.7.JNS202330DOI Listing
January 2021

Clinical and Economic Burden of Hyperkalemia: A Nationwide Hospital-Based Cohort Study in Japan.

Kidney Med 2020 Nov-Dec;2(6):742-752.e1. Epub 2020 Oct 17.

Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan.

Rationale & Objective: Hyperkalemia is a common electrolyte abnormality of chronic kidney disease and heart failure associated with increased mortality and morbidity. We aimed to assess the long-term economic burden of hyperkalemia.

Design: Observational cohort study using a Japanese nationwide hospital claims database (April 1, 2008, to September 30, 2018).

Setting & Population: : Patients 18 years or older with at least 1 serum potassium value (N = 1,208,894).

Exposures: Hyperkalemia defined with the presence of at least 2 serum potassium values ≥ 5.1 mmol/L.

Outcome Measures: Direct health care costs and resource use in patients with hyperkalemia within and after 12 months from first hyperkalemia episodes.

Analytical Approach: Health care costs and resource use were compared with propensity score-matched or nonmatched normokalemic controls. Multivariable regression analysis was performed to examine factors associated with health care costs.

Results: 27,534 patients with hyperkalemia and 233,098 normokalemic controls were studied. Mean ± SD age was 73±13 years in patients with hyperkalemia; among them, 59% and 35% had chronic kidney disease and heart failure, respectively. In the propensity score-matched cohort (n = 5,859 in each group), average numbers of hospitalizations per patient per year in patients with hyperkalemia within and after 12 months were 1.2 and 1.6 times higher, respectively, compared with those in patients with normokalemia. The total cost per patient in patients with hyperkalemia was higher than for controls, with mean differences of $8,611 (95% CI, $8,046-$9,175) within 12 months and $5,150 (95% CI, $4,733-$5,566) after 12 months. The number of repeat hyperkalemic episodes was the factor with the strongest association with long-term health care costs, whereas severity of hyperkalemia was not associated.

Limitations: This study used secondary data; therefore, residual confounders may not be fully excluded.

Conclusions: Hyperkalemia was associated with significant long-term economic burden with frequent hospitalizations due to recurrent episodes, indicating the importance of hyperkalemia treatment for the sake of reducing health economic burdens and clinical complications.
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http://dx.doi.org/10.1016/j.xkme.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729225PMC
October 2020

Optimal phase analysis of electrocardiogram-gated computed tomography angiography in patients with Stanford type A acute aortic dissection.

Eur J Radiol Open 2020 9;7:100289. Epub 2020 Dec 9.

Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan.

Objective: To determine the phase that facilitates flap observation of the ascending aorta in Stanford type A acute aortic dissection with perfused false lumen.

Methods: We reconstructed retrospective Electrocardiogram-gated Computed Tomography Angiography images of the ascending aorta of all 20 patients to 20 phases of curved-multiplanar reconstruction in 5% increment. One radiologist created and randomized 10 cross-sectional images of each phase for every patient and two radiologists scored these images on a 5-point scale depending on the degree of flap stoppage. We calculated the average score for each phase of each case and compared them among the three groups.

Results: Image scores were significantly better in the 65 %-100 % R-R interval group than those in the 5%-30 % (p < 2e-16) and 35 %-60 % R-R interval groups(p = 7.2e-10). Similar scores were observed in the Heart Rate > 70 group (p = 0.00039, 2.2e-14). Moreover a similar tendency was observed in the arrhythmia group (p = 0.0035, 0.294). No difference was found in the degree of flap stoppage in the 65 %-100 % R-R interval group between the Heart Rate > 70 and Heart Rate ≤ 70 groups (p = 0.466) and between the arrhythmia and non-arrhythmia groups (p = 0.1240).

Conclusion: In observing the ascending aorta, We obtained a good image at 65 %-100 % R-R interval and similar tendency was observed in the patients with arrhythmia.
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http://dx.doi.org/10.1016/j.ejro.2020.100289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726336PMC
December 2020

Relationships between Smoking Status, Cardiovascular Risk Factors, and Lipoproteins in a Large Japanese Population.

J Atheroscler Thromb 2020 Oct 28. Epub 2020 Oct 28.

Department of Insured Medical Care Management, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU).

Aims: Smoking is a major risk factor for cardiovascular disease (CVD), a leading cause of death and disability. Other CVD risk factors include age, gender, hypertension, diabetes, increased low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C). Our goal was to assess relationships between smoking status and CVD risk factors, with a focus on direct LDL-C, HDL-C, triglycerides (TG) and small dense LDL-C (sdLDL-C).

Methods: A total of 34,497 Japanese men and women, mean age 51 years, had their CVD risk factors including fasting serum total cholesterol, TG, HDL-C, sdLDL-C, and direct LDL-C assessed. One-way ANOVA and multiple linear regression analyses were carried to assess the interrelationships of these parameters with smoking.

Results: In both men and women, current smokers had significantly (p<0.001) higher median TG (+19.6%, +16.9%) and sdLDL-C levels (+12.7%, +4.2%) levels, and significantly (p<0.001) lower HDL-C levels (-7.3%, -4.3%) than non-smokers. They were also significantly (p<0.05) more likely to have TG values >150 mg/dL (+56.8%, +116.3%), sdLDL-C >40.1 mg/dL (+28.8%, +44.9%), and HDL-C <40 mg/dL (+89.8%, +114.3%). Ex-smokers generally had lipid values that were intermediate between non-smokers and current smokers. Multivariate analysis confirmed the significance of these relationships.

Conclusion: Our data indicate that current cigarette smoking is associated with increased TG and sdLDL-C levels, as well as decreased HDL-C levels. Furthermore, smoking effect on lipid profiles remain after cessation. These data provide further justification for smoking cessation.
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http://dx.doi.org/10.5551/jat.56838DOI Listing
October 2020

Prevalences of hyperuricemia and electrolyte abnormalities in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

PLoS One 2020 15;15(10):e0240402. Epub 2020 Oct 15.

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.

Methods: In total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.

Results: Logistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.

Conclusions: We determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561156PMC
December 2020

2018 Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C in Chronic Kidney Disease Guideline Implementation: Asia Summit Conference Report.

Kidney Int Rep 2020 Aug 21;5(8):1129-1138. Epub 2020 May 21.

Kidney Disease: Improving Global Outcomes (KDIGO), Brussels, Belgium.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.
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http://dx.doi.org/10.1016/j.ekir.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403514PMC
August 2020

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

PLoS One 2020 20;15(7):e0236132. Epub 2020 Jul 20.

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD.

Methods: In total, 31,082 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.

Results: The mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09-2.58]), G4 (5.50 [4.80-6.31]), and G5 (9.75 [8.13-11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5.

Conclusions: We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371174PMC
September 2020

Application of explainable ensemble artificial intelligence model to categorization of hemodialysis-patient and treatment using nationwide-real-world data in Japan.

PLoS One 2020 29;15(5):e0233491. Epub 2020 May 29.

Department of Nephrology, Tokyo Women's Medical University, Shinjuku, Tokyo, Japan.

Background: Although dialysis patients are at a high risk of death, it is difficult for medical practitioners to simultaneously evaluate many inter-related risk factors. In this study, we evaluated the characteristics of hemodialysis patients using machine learning model, and its usefulness for screening hemodialysis patients at a high risk of one-year death using the nation-wide database of the Japanese Society for Dialysis Therapy.

Materials And Methods: The patients were separated into two datasets (n = 39,930, 39,930, respectively). We categorized hemodialysis patients in Japan into new clusters generated by the K-means clustering method using the development dataset. The association between a cluster and the risk of death was evaluated using multivariate Cox proportional hazards models. Then, we developed an ensemble model composed of the clusters and support vector machine models in the model development phase, and compared the accuracy of the prediction of mortality between the machine learning models in the model validation phase.

Results: Average age of the subjects was 65.7±12.2 years; 32.7% had diabetes mellitus. The five clusters clearly distinguished the groups on the basis of their characteristics: Cluster 1, young male, and chronic glomerulonephritis; Cluster 2, female, and chronic glomerulonephritis; Cluster 3, diabetes mellitus; Cluster 4, elderly and nephrosclerosis; Cluster 5, elderly and protein energy wasting. These clusters were associated with the risk of death; Cluster 5 compared with Cluster 1, hazard ratio 8.86 (95% CI 7.68, 10.21). The accuracy of the ensemble model for the prediction of 1-year death was 0.948 and higher than those of logistic regression model (0.938), support vector machine model (0.937), and deep learning model (0.936).

Conclusions: The clusters clearly categorized patient on their characteristics, and reflected their prognosis. Our real-world-data-based machine learning system is applicable to identifying high-risk hemodialysis patients in clinical settings, and has a strong potential to guide treatments and improve their prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233491PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259704PMC
August 2020

J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan.

Sci Rep 2020 04 30;10(1):7351. Epub 2020 Apr 30.

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan.

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39,121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1,001 (2.6%), 2,612 (6.7%), 23,333 (59.6%), 8,357 (21.4%), 2,710 (6.9%) and 1,108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care.
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http://dx.doi.org/10.1038/s41598-020-64123-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192920PMC
April 2020

Postdialysis blood pressure is a better predictor of mortality than predialysis blood pressure in Japanese hemodialysis patients: the Japan Dialysis Outcomes and Practice Patterns Study.

Hypertens Res 2020 08 19;43(8):791-797. Epub 2020 Mar 19.

Fukuoka Renal Clinic, Fukuoka, Japan.

Blood pressure (BP) is reportedly a predictor of mortality in hemodialysis (HD) patients; however, it is unclear whether pre- or postdialysis BP has greater predictive power. To evaluate the association of pre- and postdialysis BP with patient survival in Japanese HD patients, we enrolled the entire phase 3 and 4 Japan Dialysis Outcomes and Practice Patterns Study populations. Among 3176 patients, 486 were excluded because of missing data. The remaining 2690 patients were divided into five groups according to pre- or postdialysis systolic BP (SBP): <100, 100-119, 120-139, 140-159, and ≥160 mmHg; diastolic BP (DBP): <60, 60-79, 80-89, 90-99, and ≥100 mmHg; or pulse pressure (PP): <50, 50-59, 60-69, 70-79, and ≥80 mmHg. The hazard ratios for all-cause and cardiovascular mortalities were estimated according to pre- and postdialysis SBP, DBP, and PP using a Cox proportional hazards model. During the follow-up period, 495 and 193 subjects died because of any cause and cardiovascular disease (CVD), respectively. In the multivariable-adjusted Cox proportional hazards model, U-shaped associations of postdialysis SBP and PP with mortality rates were observed, but no significant associations were observed with predialysis SBP or PP. A stratified analysis showed significant interactions between history of CVD and postdialysis SBP with all-cause and cardiovascular mortality. Compared with predialysis values, postdialysis SBP and PP are better predictors of all-cause and cardiovascular mortality, showing U-shaped associations with these outcomes in Japanese HD patients.
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http://dx.doi.org/10.1038/s41440-020-0425-1DOI Listing
August 2020

The Normalized Protein Catabolic Rate and Mortality Risk of Patients on Hemodialysis by Frailty Status: The Japanese Dialysis Outcomes and Practice Pattern Study.

J Ren Nutr 2020 11 29;30(6):535-539. Epub 2020 Feb 29.

Department of Medicine, Kidney Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.

Objective: The appropriate protein intake for patients on hemodialysis complicated with frailty remains highly controversial.

Methods: We conducted a prospective cohort study using data from Japanese Dialysis Outcomes and Practice Pattern Study. The patients were separated by their baseline of normalized protein catabolic rate (nPCR) into 3 categories: low (nPCR < 1.0), medium (1.0 ≤ nPCR <1.2), and high (nPCR ≥1.2). The frailty score was calculated based on the 12-item Short Form, and frailty was defined in cases with a total score of ≥2 points. The all-cause mortality was compared between groups using a Cox proportional hazard model.

Results: A total of 2,404 patients were included in the longitudinal analysis, 1,096 (45.6%) of whom had frailty. Patients in the low-nPCR group showed a higher prevalence of frailty than those in the other groups. In the Cox proportional hazard model, no significant differences in the all-cause mortality were noted between the low-nPCR and medium-nPCR groups or the high-nPCR and medium-nPCR groups. Furthermore, no significant differences were noted among any groups when subjects were limited to patients with frailty.

Conclusions: Patients with a low nPCR have a higher prevalence of frailty and incidence of mortality than those with a medium nPCR. Patients with a high nPCR did not show a lower survival rate than those with a medium nPCR in this study. To clarify the appropriate protein intake for patients on hemodialysis with frailty, an intervention study or large-scale, long-term cohort study will be needed.
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http://dx.doi.org/10.1053/j.jrn.2019.12.005DOI Listing
November 2020

Increased plasma plasmin-α2-plasmin inhibitor complex levels correlate with postoperative rebleeding after endoscopic surgery for spontaneous intracerebral hemorrhage.

Acta Neurochir (Wien) 2020 12 28;162(12):3129-3136. Epub 2019 Nov 28.

Department of Neurosurgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.

Background: Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear.

Objective: This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR.

Methods: A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated.

Results: PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 μg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 μg/ml and ≥ 6 μg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 μg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65-98.77; p = 0.02) or ≥ 6 μg/ml (OR, 18.33; 95% CI, 2.32-144.82; p = 0.006) were independent predictors of PR.

Conclusions: This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.
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http://dx.doi.org/10.1007/s00701-019-04154-2DOI Listing
December 2020

Impact of Bladder Neck Involvement on Recurrence in Patients With Non-muscle-invasive Bladder Cancer: An Analysis Based on a Time-dependent Model.

Clin Genitourin Cancer 2020 04 16;18(2):e62-e70. Epub 2019 Oct 16.

Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. Electronic address:

Background: Tumor location in bladder neck has reported to be a prognostic factor for non-muscle-invasive bladder cancer (NMIBC). We investigated the impact of bladder neck involvement (BNI) on recurrence in NMIBC using time-dependent covariate analysis.

Patients And Methods: We enrolled 585 Japanese patients who underwent transurethral resection for bladder tumors at a single center from 2000 to 2016 and were pathologically diagnosed with Ta and T1 NMIBC. Each patient at each recurrence was assigned to a separate time-dependent stratum with its own baseline hazard function according to the Prentice-Williams-Peterson gap time model for analyzing recurrent events.

Results: Over a median follow-up period of 41.3 months (interquartile range, 18.0-82.3 months), 253 (43.2%) patients experienced a total of 475 recurrences. Among the 1001 total transurethral resection procedures, BNI was observed in 122 (12.2%) cases. The 3-year cumulative recurrence rates of patients with and without BNI were 62.5% and 46.3%, respectively. Multivariable analysis revealed that number of tumors ≥ 4 (sub-hazard ratio [SHR], 1.48; P = .004), intravesical bacillus Calmette-Guérin therapy (SHR, 0.44; P < .001), and BNI (SHR, 1.59; P = .004) were all independent predictors of recurrence. Assigning 1 point for each of these 3 predictive factors, the resulting scores enabled us to classify patients into 3 prognostic groups that were clearly stratified according to recurrence.

Conclusions: Our time-dependent covariate analysis shows that BNI is a significant risk factor for recurrence in NMIBC. Our prognostic model incorporating BNI is an easy means of estimating recurrence risk and determining optimal management for individual patients.
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http://dx.doi.org/10.1016/j.clgc.2019.10.005DOI Listing
April 2020

Renoprotective effects of sodium-glucose cotransporter-2 inhibitors and underlying mechanisms.

Curr Opin Nephrol Hypertens 2020 01;29(1):112-118

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.

Purpose Of Review: Emerging data have demonstrated that sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent cardiovascular events, especially heart failure-associated endpoints. Cardiovascular outcome trials have also suggested their renoprotective effects. One large clinical trial investigated renal primary endpoints and demonstrated that SGLT2 inhibitors slowed the progression of diabetic kidney disease (DKD). This review summarizes clinical trial data on renal outcomes and discusses potential underlying mechanisms.

Recent Findings: The EMPA-REG, CANVAS, and DECLARE-TIMI 58 studies revealed that SGLT2 inhibitors reduce the risk of cardiovascular events and concomitantly suggested that these drugs slow the progression of kidney disease in type 2 diabetes. The CREDENCE trial on patients with high-risk type 2 diabetes and chronic kidney disease demonstrated that canagliflozin treatment reduced the relative risk of a composite outcome, including end-stage kidney disease, serum creatinine doubling, and renal/cardiovascular death, by 30% in these patients. Animal experiments revealed that oxidative stress, inflammation, fibrosis, and tubuloglomerular feedback are underlying renoprotective mechanisms behind SGLT2 inhibitors.

Summary: Recent clinical trials have established the renoprotective effects of SGLT2 inhibitors. Further investigations on mechanisms of these renoprotective effects will provide deeper insights and understanding of pathogenetic properties of DKD.
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http://dx.doi.org/10.1097/MNH.0000000000000561DOI Listing
January 2020

[Relationship between Coombs-positive autoimmune hemolytic anemia and development of malignant tumors: a retrospective study].

Rinsho Ketsueki 2019 ;60(10):1418-1424

Department of Hematology, Kawasaki Medical School.

Autoimmune hemolytic anemia (AIHA) is secondary to underlying diseases, such as autoimmune diseases and lymphoid malignancies. Recently, solid cancers have also been reported to be associated with AIHA, although there is not much information available. In this study, we retrospectively examined the correlation between AIHA and onset of malignancy in 100 patients diagnosed with AIHA based on the broad definition of AIHA at our hospital and cooperating institutions from January 1, 1995 to May 31, 2016. Malignancies were detected in 52 of the 100 patients (hematological malignancies: 39 patients; solid cancers: 22 patients; total malignancies including multiple primary malignancies: 67 patients). Of the 67 patients with malignancies, 28 were diagnosed with malignancies within 6 months of AIHA diagnosis. All patients with cold agglutinin disease (CAD) were associated with malignancies. Compared with warm AIHA, solid cancers were significantly more common among the patients with CAD. These findings emphasize the importance of investigating the malignancies upon diagnosis of AIHA.
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http://dx.doi.org/10.11406/rinketsu.60.1418DOI Listing
November 2019

Hyperkalemia in Real-World Patients Under Continuous Medical Care in Japan.

Kidney Int Rep 2019 Sep 30;4(9):1248-1260. Epub 2019 May 30.

Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan.

Introduction: An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied.

Methods: An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008-September 2017;  = 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed.

Results: Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1-68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3-231.5), heart failure (134.0; 95% CI: 131.2-136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6-144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1-5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2-8.0). The 3-year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1-5.4, 5.5-5.9, and ≥6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K (≥5.1 mEq/l).

Conclusion: This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds.
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http://dx.doi.org/10.1016/j.ekir.2019.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734103PMC
September 2019

Potential Impact on Lipoprotein Subfractions in Type 2 Diabetes.

Clin Med Insights Endocrinol Diabetes 2019 14;12:1179551419866811. Epub 2019 Aug 14.

Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Introduction: Recently, the sodium-glucose cotransporter2 (SGLT2) inhibitor empagliflozin has been shown to lower cardiovascular risk among diabetic patients. It is intriguing that some SGLT2 inhibitors have been found to increase low-density lipoprotein (LDL) cholesterol levels, while the relevance to high-density lipoprotein (HDL) cholesterol is unknown. Although the inhibitory effect of SGLT2 inhibitors on glucose reabsorption may accelerate compensatory lipid metabolism and subsequently reduce body weight and affect the lipid profile, much remains unclear about this mechanism. Therefore, we conducted this study to investigate in detail how canagliflozin affects lipoprotein fractions including LDL and HDL subclasses.

Materials And Methods: This study is a multicenter prospective study. The participants were patients with 22 type 2 diabetes (60.7 ± 11.6 years, 59.1% of men) who had HbA1c ⩾ 7.0% and consented to participate in the study. They were administered 100 mg canagliflozin orally once per day. Biochemistry test and cholesterol levels of 20 lipoprotein fractions (G1-G20) using high performance liquid chromatography methods were examined before and after 12 weeks of treatment period.

Results: Significant decreases were observed in the participants' body weight (69.7 to 67.9 kg, < .001), systolic blood pressure (129.3 to 119.5 mm Hg, < .01), and HbA1c (8.5% to 7.4%, < .001). Cholesterol levels in the 20 lipoprotein fractions increased for very large HDL (G14, G15) and large HDL (G16) ( < .05).

Conclusions: Reduction in body weight, improvement of blood glucose levels, and increases in very large HDL and large HDL subclasses were observed after canagliflozin treatment. These beneficial changes might contribute to subsequent suppression of cardiovascular outcomes.
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http://dx.doi.org/10.1177/1179551419866811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696845PMC
August 2019

Are SGLT2 inhibitors a targeted treatment for diabetic kidney disease?

Kidney Int 2019 07;96(1):8-10

Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.kint.2019.04.005DOI Listing
July 2019

A new nutritional risk index for predicting mortality in hemodialysis patients: Nationwide cohort study.

PLoS One 2019 28;14(3):e0214524. Epub 2019 Mar 28.

Department of Nephrology, Tokyo Medical University, Shinjuku, Tokyo, Japan.

Background: Protein energy wasting (PEW) is a risk factor for death. However, the cutoff vales for PEW are not optimized for early identification of hemodialysis patients with malnutrition. We evaluated the prognosis of Japanese maintenance hemodialysis patients using nutritional indices optimized for them.

Materials And Methods: We analyzed data from a nation-wide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry to develop and validate a nutritional risk index (n = 48349, 48349, respectively). The association of nutritional factors with one-year death was tested using Cox proportional hazards models. Their cutoff levels were determined from the hazard ratios or receiver operating characteristic curves. Then, risk index was developed using scoring models.

Results: Male was 61.4%; average age, 65.7±12.2 years; and diabetes mellitus, 32.8%. Four clinical factors were retained in the final model: low BMI (<20kg/m2), yes = 3, no = 0; low serum albumin level (young <3.7g/dL; old <3.5g/dL), yes = 4, no = 0; abnormal serum total cholesterol level, low (<130mg/dL) = 1, high (220≥mg/dL) = 2, no = 0; low serum creatinine level (young female, <9.7mg/dL; old female, <8.0mg/dL; young male, <11.6mg/dL; old male, <9.7mg/dL), yes = 4, no = 0. In the validation dataset, medium- and high-risk groups (total score 8 to 10; 11 or more) showed a higher risk of all-cause death than the low-risk group (0 to 7): medium-risk group (10.5%), hazard ratio adjusted for baseline characteristics 1.96 (95% confidence interval 1.77, 2.16); high-risk group (8.2%), 3.91 (3.57, 4.29). The medium- and high-risk groups also showed a higher risk of cardiovascular disease- and infection-caused deaths than the low-risk group.

Conclusion: We developed a new nutritional risk index for hemodialysis patients, which may detect patients with malnutrition with a high-risk of death.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214524PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438476PMC
December 2019

Identifying progressive CKD from healthy population using Bayesian network and artificial intelligence: A worksite-based cohort study.

Sci Rep 2019 03 25;9(1):5082. Epub 2019 Mar 25.

Sports Medical Research Center, Keio University, Kanagawa, Japan.

Identifying progressive early chronic kidney disease (CKD) patients at a health checkup is a good opportunity to improve their prognosis. However, it is difficult to identify them using common health tests. This worksite-based cohort study for 7 years in Japan (n = 7465) was conducted to evaluate the progression of CKD. The outcome was aggravation of the KDIGO prognostic category of CKD 7 years later. The subjects were male, 59.1%; age, 50.1 ± 6.3 years; and eGFR, 79 ± 14.4 mL/min/1.73 m. The number of subjects showing CKD progression started to increase from 3 years later. Vector analysis showed that CKD stage G1 A1 was more progressive than CKD stage G2 A1. Bayesian networks showed that the time-series changes in the prognostic category of CKD were related to the outcome. Support vector machines including time-series data of the prognostic category of CKD from 3 years later detected the high possibility of the outcome not only in subjects at very high risks but also in those at low risks at baseline. In conclusion, after the evaluation of kidney function at a health checkup, it is necessary to follow up not only patients at high risks but also patients at low risks at baseline for 3 years and longer.
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http://dx.doi.org/10.1038/s41598-019-41663-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434140PMC
March 2019

Use of vasopressor for dialysis-related hypotension is a risk factor for death in hemodialysis patients: Nationwide cohort study.

Sci Rep 2019 03 4;9(1):3362. Epub 2019 Mar 4.

Department of Nephrology, Honcho Yabuki Clinic, Yamagata, Japan.

Because hypotension during hemodialysis (HD) makes continuation of HD difficult and is associated with mortality, pressor approaches are necessary for patients with hypotension. However, the relationships between the pressor approaches and the risk of death have not been clarified yet. We analyzed data from a nationwide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (n = 29,309). The outcome was all-cause one-year death. The association between the use of pressor approaches and the outcome was examined using Cox proportional hazards models adjusted for baseline characteristics, propensity score matched analysis and Bayesian networks. The background features of the patients were as follows: male, 59.6%; average age, 64.5 ± 12.5 years; and patients with diabetes mellitus, 31.5%. The pressor group showed a higher risk of the outcome than the control group [adjusted hazard ratio (aHR) 1.33 (95% CI: 1.21, 1.47), p = 0.0001]. Propensity score matched analysis also showed that the matched-pressor group had a higher risk of the outcome than the matched-control group [aHR 1.30 (95% CI: 1.17, 1.45), p = 0.0001]. Moreover, the Bayesian network showed a direct causal relationship from the use of pressor approaches to the outcome. The use of oral vasopressors [aHR 1.20 (95% CI: 1.07, 1.35), p = 0.0018], intravenous injection of vasopressors [aHR 1.54 (95% CI: 1.32, 1.79), p = 0.0001] and normal saline [aHR 1.18 (95% CI: 1.05, 1.33), p = 0.0066] were associated with a high risk of the outcome. In conclusion, this study showed that the use of pressor approaches during HD may be an independent risk factor for death.
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http://dx.doi.org/10.1038/s41598-019-39908-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399330PMC
March 2019