Kenjiro Kimura

Japan Community Healthcare Organization Sapporo Hokushin Hospital, Sapporo, Hokkaidō, Japan

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Publications (189)518.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Tumor necrosis factor (TNF)-α is suggested to induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells that possibly exacerbates renal interstitial fibrosis in glomerulonephritis (GN). We here investigated whether layilin (LAYN), a c-type lectin-homologous protein, was involved in the EMT process. Methods: Expression of LAYN was investigated in kidneys of mice administered with TNF-α and in a clear cell renal carcinoma cell line of KMRC-1 stimulated with TNF-α by quantitative polymerase chain reaction (qPCR) and/or western blotting. Expression of LAYN was assessed immunohistochemically in renal biopsy samples of patients with various types of GN. Changes of EMT markers and cell morphology by TNF-α and transforming growth factor (TGF)-β in LAYN-knocked down KMRC-1 cells were investigated by qPCR and immunocytochemistry. Results: Administration of TNF-α increased expression of LAYN in renal tubular epithelia in mice. TNF-α but not TGF-β increased expression of LAYN in KMRC-1 cells. Renal biopsy samples from the patients with GN showed high expression of LAYN in tubular epithelial cells. TNF-α induced up-regulation of vimentin, down-regulation of E-cadherin, and fibroblast-like morphological change in KMRC-1 cells, indicating occurrence of EMT. These changes were not observed in the LAYN-knocked down cells. In contrast, similarly occurred TGF-β-induced EMT was not affected by the LAYN knockdown. Conclusion: Our data indicate that LAYN is involved in the TNF-α-induced EMT of renal tubular epithelial cells. LAYN may play roles in the generation of renal interstitial fibrosis in GN via TNF-α-induced EMT.
    Biochemical and Biophysical Research Communications 09/2015; DOI:10.1016/j.bbrc.2015.09.121 · 2.30 Impact Factor
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    ABSTRACT: Background/Aims: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. Methods: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. Results: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level Conclusions: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.
    08/2015; 5(2):58-66. DOI:10.1159/000437338
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    ABSTRACT: Contrast medium (CM) induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP) increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP). Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29). Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Urinary L-FABP levels were significantly higher at 12 hours (P<0.05) and 24 hours (P<0.005) after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17), but not in those without cardiovascular events (n=12). The parameter with the largest area under the curve (0.816) for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 μg/g creatinine) between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27-19.13; P=0.021). Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk stratification of onset of cardiovascular events.
    International Journal of Nephrology and Renovascular Disease 08/2015; 8:91-9. DOI:10.2147/IJNRD.S88467
  • Keita Uehara · Takashi Yasuda · Yugo Shibagaki · Kenjiro Kimura
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    ABSTRACT: We often experience visit-to-visit estimated glomerular filtration rate (eGFR) variability among patients with advanced chronic kidney disease (CKD). However, the impact of eGFR variability on renal prognosis is not well understood. The Kanagawa Valsartan Trial was a multicenter, randomized, open-label trial that compared the effect of add-on treatment with angiotensin II receptor blocker, valsartan, with that of conventional treatment on the rate of CKD progression in 293 advanced CKD patients. In this post hoc analysis, we compared the effect of high eGFR variability on end-stage renal disease (ESRD). To evaluate eGFR variability, we chose participants with ≥5 serial measurements of eGFR during the study period and assessed the residual coefficient of variation (CV) of eGFR (residual eGFR-CV) derived from a regression line of eGFR (eGFR slope). The primary end point was the first event of ESRD. Among 237 patients with ≥5 serial measurements of eGFR in a median follow-up of 1.47 years, there were 54 ESRD events in the higher than median residual eGFR-CV group and 36 ESRD events in the lower than median eGFR-CV group (log-rank test, p = 0.008). In multivariate Cox regression analysis, high eGFR variability was significantly associated with the primary end point as well as hypertension, high proteinuria, low baseline eGFR and steep eGFR slope (hazards ratio 2.11, 95% CI 1.33-3.33, p = 0.001). High eGFR variability predicts poor renal prognosis; therefore, further attention is warranted for ambulatory patients with large eGFR fluctuations, especially those with advanced CKD. © 2015 S. Karger AG, Basel.
    07/2015; 130(4). DOI:10.1159/000438460
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    ABSTRACT: To improve outcomes in patients with chronic kidney disease (CKD), it is important to identify prognostic factors for end-stage renal disease (ESRD) as well as cardiovascular disease (CVD). This study assessed urinary concentrations of albumin, N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP), as predictors of ESRD and CVD. A prospective, observational, multicenter study, comprising 244 Japanese outpatients with CKD who had a follow-up period of at least 3 months. The primary endpoint was the first onset of a nonfatal or fatal CVD event and progression to ESRD, defined as myocardial infarction, stroke, or artery revascularization (coronary, carotid or peripheral), and initiation of dialysis. During a median follow-up of 3.8 years, the primary endpoint occurred in 39 (15.8 %) patients. Irrespective of diabetes, high urinary L-FABP correlated with the development of ESRD and CVD. The areas under the receiver-operator characteristic curves (AUCs) for predicting the primary endpoint for urinary concentrations of L-FABP, albumin, and NAG were 0.825, 0.797, and 0.722, respectively. Cox regression analyses, which were adjusted for factors known to influence the primary endpoint, including patient characteristics, and serum and urinary parameters, demonstrated that the primary outcome was associated with high urinary L-FABP and low eGFR [p = 0.049, hazard ratio = 1.341 (95 % CI 1.005-1.790); and p < 0.000, hazard ratio = 0.953 (95 % CI 0.930-0.976), respectively]. Urinary L-FABP may be a useful prognostic marker of progression to ESRD and the onset of CVD in patients with CKD.
    Clinical and Experimental Nephrology 07/2015; DOI:10.1007/s10157-015-1144-9 · 2.02 Impact Factor
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    ABSTRACT: The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. Longitudinal cohort study. 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. Quartiles of TG:HDL-C ratio. Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. Short observation period and single measurement of all variables. A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 07/2015; DOI:10.1053/j.ajkd.2015.05.011 · 5.90 Impact Factor
  • Naohiko Imai · Ryo Zamami · Kenjiro Kimura
    Indian journal of dermatology, venereology and leprology 06/2015; 81(4). DOI:10.4103/0378-6323.158664 · 1.39 Impact Factor
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    ABSTRACT: Here we report therapeutic drug monitoring of cyclosporine in a kidney transplant recipient lacking enterohepatic circulation. The patient developed steroid-resistant nephrotic syndrome at age 14 years, and was medicated with an oral cyclosporine microemulsion. However, her cyclosporine trough level was unexpectedly elevated, and subsequent investigations showed that she was deficient in drug metabolism as a result of the congenital absence of the portal vein. Her renal function gradually decreased and she became dialysis-dependent at the age of 21 years, and kidney transplantation was planned. Based on pretransplant therapeutic drug monitoring, we started cyclosporine microemulsion at half of the conventional dosage. After transplantation, the dosage was successfully adjusted to achieve a target trough level. The post-transplant course was stable with no symptoms of rejection or cyclosporine-associated nephrotoxicity. © 2015 The Japanese Urological Association.
    International Journal of Urology 06/2015; 22(8). DOI:10.1111/iju.12830 · 2.41 Impact Factor
  • Naohiko Imai · Kenjiro Kimura
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    ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print., *2007 Journal Citation Report (Thomson Reuters, 2008)
    The American Journal of Gastroenterology 06/2015; 110(6):799. DOI:10.1038/ajg.2014.332 · 10.76 Impact Factor
  • Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 05/2015; 35(3):360-361. DOI:10.3747/pdi.2013.00313 · 1.53 Impact Factor
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    ABSTRACT: Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients. A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated. Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001) and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001) were significant predictors of urinary L-FABP levels. Urinary L-FABP is strongly associated with anemia in non-diabetic patients.
    PLoS ONE 05/2015; 10(5):e0126990. DOI:10.1371/journal.pone.0126990 · 3.23 Impact Factor
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    ABSTRACT: Treatment of congestive heart failure (CHF) with loop diuretics, such as furosemide, may be associated with complications, including worsening renal function and metabolic or electrolyte disturbances. Coadministration of tolvaptan, a selective vasopressin V2 receptor antagonist, can ameliorate such adverse events by reducing the required dose of loop diuretics; however, the safety of tolvaptan in patients with reduced renal function is not known. As a result, we conducted an exploratory clinical trial of tolvaptan in 22 patients with CHF and advanced chronic kidney disease (CKD). We classified these patients into three groups according to their estimated glomerular filtration rate, namely, CKD stages G3b, G4, and G5. Patients were coadministered tolvaptan 15 mg once daily for 7 days after single administration of furosemide. We assessed patients' hemodynamic parameters, serum chemistry values, and body fluid status during the study. On day 8, serum sodium and potassium concentrations were significantly higher than baseline values in the G3b (p = 0.020) and G5 groups (p = 0.037), respectively. Although serum urea nitrogen and creatinine concentrations increased significantly in the G4 group (p = 0.017 and p = 0.012, respectively), no patient in any of the three groups showed decreased renal function on days 2 and 3. In addition, no significant changes in serum uric acid, blood pressure, or heart rate were observed in any patient in this study. In this short-term pilot study, coadministration of tolvaptan and furosemide appears to be safe in patients with heart failure and CKD.
    Clinical nephrology 05/2015; 84(1). DOI:10.5414/CN108457 · 1.13 Impact Factor
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    ABSTRACT: A 62-yearold man was diagnosed with peritoneal dialysis (PD)-related peritonitis following diarrhea and determination of a dialysate leukocyte count of 10,224/μL. We cultured peritoneal effluent and started intraperitoneal antibiotic therapy. Peritonitis immediately improved. Peritoneal effluent culture yielded Aeromonas hydrophila. The medical interview revealed that the patient kept goldfish as pets. We suspected that the fish tank water was the source of the infection, considering the association of A. hydrophila with aquatic environments. Culturing of tank water confirmed the presence of Aeromonas. Furthermore, we observed that one of the goldfish was suffering from lepidorthosis, which is commonly caused by Aeromonas, and we then confirmed that the fish's infection was caused by an aeromonad. Aeromonas species have rarely been identified as the pathogens in PDrelated peritonitis; to our knowledge, there hitherto have been no reports identifying the source of this organism. We present here the process of this infection as elucidated through investigation of the living environment of the patient.
    Clinical nephrology 05/2015; 84(1). DOI:10.5414/CN108459 · 1.13 Impact Factor
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    ABSTRACT: Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate<60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at baseline and during 3 annual follow-up visits (4 visits). BP variability was defined as standard deviation (SD) and average real variability during the 4 visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD. In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11-1.20], 1.08 [1.04-1.12], 1.13 [1.09-1.17], 1.06 [1.02-1.10], respectively; all P<0.01) after adjustment for clinical characteristics, and with mean BP from year 0 to year 3. The associations of SDBP and average real variabilityBP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06-1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive medication use, and the presence of hypertension showed similar conclusions. Among those in the middle-aged and elderly general population without diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up. © 2015 American Heart Association, Inc.
    Hypertension 05/2015; 66(1). DOI:10.1161/HYPERTENSIONAHA.115.05472 · 6.48 Impact Factor
  • International journal of cardiology 05/2015; 191:198-200. DOI:10.1016/j.ijcard.2015.05.005 · 4.04 Impact Factor
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    ABSTRACT: AimTreatment with telaprevir (TVR) entails adverse side effects including anemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C.Methods Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (1) patients with an increase in SCr during the treatment (n=8) and (2) patients without an increase in SCr (n=5). Urine and serum parameters were evaluated.ResultsAlthough there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase-in-SCr group during the triple therapy. The SCr level returned to the pre-treatment level after cessation of TVR. There were no differences in urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre-treatment tended to be higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR.Conclusion Elevation of SCr levels with TVR therapy may not suggest renal impairment.
    Nephrology 05/2015; DOI:10.1111/nep.12517 · 2.08 Impact Factor
  • International journal of cardiology 03/2015; 187(1):648-650. DOI:10.1016/j.ijcard.2015.03.387 · 4.04 Impact Factor
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    ABSTRACT: Hypouricemia, conventionally defined as a serum uric acid level of ≤2 mg/dl, is considered a biochemical disorder with no clinical significance. However, individuals with renal hypouricemia have a high risk of urolithiasis and exercise-induced acute kidney injury, both of which are risk factors for reduced kidney function. To test the hypothesis that individuals with hypouricemia would be at a higher risk of reduced kidney function, we conducted a population-based cross-sectional study using data from the Specific Health Checkups and Guidance System in Japan. Logistic analysis was used to examine the relationship between hypouricemia and reduced kidney function, defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2). Among 90,710 men (mean age, 63.8 years) and 136,935 women (63.7 years), 193 (0.2%) and 540 (0.4%) were identified as having hypouricemia, respectively. The prevalence of hypouricemia decreased with age in women (p for trend <0.001), but not in men (p for trend = 0.24). Hypouricemia was associated with reduced kidney function in men (odds ratio, 1.83; 95% confidence interval, 1.23-2.74), but not in women (0.61; 0.43-0.86), relative to the reference category (i.e., serum uric acid levels of 4.1-5.0 mg/dl) after adjusting for age, drinking, smoking, diabetes, hypertension, hypercholesterolemia, obesity, and history of renal failure. Sensitivity analyses stratified by diabetic status yielded similar results. This study is the first to provide evidence that hypouricemia is associated with reduced kidney function in men. Further research will be needed to determine the long-term prognosis of individuals with hypouricemia. © 2015 S. Karger AG, Basel.
    American Journal of Nephrology 03/2015; 41(2):138-146. DOI:10.1159/000381106 · 2.67 Impact Factor
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    ABSTRACT: Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email:
    American Journal of Hypertension 02/2015; 28(9). DOI:10.1093/ajh/hpv003 · 2.85 Impact Factor
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    ABSTRACT: Case 1 : A man in his 60s who had started peritoneal dialysis (PD) for diabetic nephropathy came to hospital due to abdominal pain 58 months after beginning PD. He was diagnosed with an incarcerated right inguinal hernia by marked bulging and tenderness of the right groin. The abdominal pain was immediately improved after manual repositioning by a surgeon. However, he underwent hernia repair surgery because of the risk of recurrence. He then resumed PD on postoperative day 2. Case 2 : A woman in her 50s came to the hospital due to abdominal pain 44 months after starting PD for chronic glomerulonephritis. At the visit, she was suspected of having peritonitis. However, her umbilicus was bulging slightly and abdominal CT showed an incarcerated umbilical hernia. Emergency surgery was performed that day, and PD was resumed on postoperative day 9. Incarcerated inguinal hernias can be easily diagnosed by the presence of prolapsed organs. However, an incarcerated umbilical hernia might be misdiagnosed as peritonitis because a prolapsed organ cannot always be confirmed.
    Nihon Toseki Igakkai Zasshi 01/2015; 48(5):315-320. DOI:10.4009/jsdt.48.315

Publication Stats

2k Citations
518.26 Total Impact Points


  • 2015
    • Japan Community Healthcare Organization Sapporo Hokushin Hospital
      Sapporo, Hokkaidō, Japan
  • 2003–2015
    • St. Marianna University School of Medicine
      • • Department of Internal Medicine
      • • Clinical Proteomics and Molecular Medicine
      • • Department of Dermatology
      • • Department of Anatomy
      • • Institute of Medical Science
      Kawasaki Si, Kanagawa, Japan
  • 2014
    • Ministry of Health, Labour and Welfare - Japan
      Edo, Tōkyō, Japan
  • 2010
    • Kawasaki Municipal Hospital
      Kawasaki Si, Kanagawa, Japan
  • 1989–2008
    • The University of Tokyo
      • • Division of Internal Medicine
      • • Department of Cardiovascular Medicine
      • • School of Medicine
      Tōkyō, Japan
  • 2006
    • Kyoto Prefectural University of Medicine
      • Division of Hypertension and Nephrology
      Kioto, Kyōto, Japan
  • 2002
    • Gunma University
      Maebashi, Gunma Prefecture, Japan
  • 1995–2001
    • Juntendo University
      • Department of Medicine
      Edo, Tōkyō, Japan