Faculty Profiles - IMAIZUMI Takahiro

Unfavorable effects of history of volume overload and late referral to a nephrologist on mortality in patients initiating dialysis: a multicenter prospective cohort study in Japan

Okazaki, M; Inaguma, D; Imaizumi, T; Kada, A; Yaomura, T; Tsuboi, N; Maruyama, S

BMC NEPHROLOGY Vol. 19 ( 1 ) page： 65 2018.3

Language：English Publisher：BMC Nephrology

Background: Patients with late referral and positive history of volume overload may have a poor prognosis after initiating dialysis due to insufficient and/or inadequate management of complications of renal failure and the lack of better dialysis preparation. Little is known about the influence of the relationship between history of volume overload and late referral on prognosis. Methods: We analyzed 1475 patients who had initiated dialysis for the first time from October 2011 to September 2013. late referral was defined as referral to a nephrologist < 3 months before dialysis initiation. The major outcomes were all-cause death and deaths due to cardiovascular diseases (CVD). The impact of late referral and history of volume overload on all-cause mortality was assessed by Cox proportional hazards models. Results: Among 1475 patients, the mean patient age was 67.5 years. During the median follow-up of 2.2 years, 260 deaths occurred; 99 were due to CVD. Cox proportional hazards models demonstrated that late referral (adjusted hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.00-1.82) and history of volume overload (adjusted HR, 1.39; 95% CI, 1.06-1.81) were risk factors for all-cause mortality. Furthermore, late referral coexisting was associated with a history of volume overload increased mortality (adjusted HR, 2.10; 95% CI, 1.39-3.16 versus absence of late referral without history of volume overload) after adjusting for age, sex, diabetes, atherosclerotic disease, and laboratory values. Conclusions: Both late referral and history of volume overload were associated with increased risks of all-cause mortality. Trial registration: University Hospital Medical Information Network (UMIN000007096). Registered 18 January 2012, retrospectively registered. https://upload.umin.ac.jp/cgi-open-bin/ctr-e/ctr-view.cgi?recptno=R000008349.

DOI： 10.1186/s12882-018-0859-8

Effect of dietary energy and polymorphisms in &ITBRAP&IT and &ITGHRL&IT on obesity and metabolic traits

Imaizumi, T; Ando, M; Nakatochi, M; Yasuda, Y; Honda, H; Kuwatsuka, Y; Kato, S; Kondo, T; Iwata, M; Nakashima, T; Yasui, H; Takamatsu, H; Okajima, H; Yoshida, Y; Maruyama, S

OBESITY RESEARCH & CLINICAL PRACTICE Vol. 12 ( 1 ) page： 39 - 48 2018.1

Language：English Publisher：Obesity Research and Clinical Practice

Objective: Obesity, a risk factor for all-cause and cardiovascular mortality, is a major health concerns among middle-aged men. The aim of this study was to investigate a possible association of dietary habits and obesity related single nucleotide polymorphisms (SNPs) with obesity and metabolic abnormalities. Methods: We conducted a retrospective cohort study using annual health examination data of 5112 male workers, obtained between 2007 and 2011. Average dietary energy was estimated using electronically collected meal purchase data from cafeteria. We examined 8 SNPs related to obesity: GHRL rs696217, PPARG rs1175544, ADIPOQ rs2241766, ADIPOQ rs1501299, PPARD rs2016520, APOA5 rs662799, BRAP rs3782886, and ITGB2 rs235326. We also examined whether SNPs that were shown to associate with obesity affect other metabolic abnormalities such as blood pressure (BP), glucose, and lipid profile. Results: Average dietary energy significantly associated with increased abdominal circumference (AC) and body mass index (BMI). The odds ratios (ORs) of overweight and obesity also increased. The major allele of rs696217 significantly increased BMI and an increased OR with obesity, while the minor allele of rs3782886 was associated with significantly decreased AC and the decreased ORs with overweight and obesity. The minor allele of rs3782886 was also associated with significantly decreased systolic BP (SBP), triglyceride (TG), high-density lipoprotein (HDL), and fasting blood sugar (FBS), while rs696217 was not associated with other metabolic abnormalities. Conclusions: Average dietary energy in lunch, rs3782886, and rs696217 were associated with obesity, and rs3782886 was associated with other metabolic abnormalities.

DOI： 10.1016/j.orcp.2016.05.004

Urinary and circulating levels of the anti-angiogenic isoform of vascular endothelial growth factor-A in patients with chronic kidney disease

Kikuchi, R; Yasuda, Y; Nakatochi, M; Shibata, Y; Hara, T; Suzuki, A; Imaizumi, T; Suzuki, S; Ishii, H; Takeshita, K; Matsushita, T; Maruyama, S; Murohara, T

CLINICA CHIMICA ACTA Vol. 475 page： 102 - 108 2017.12

Language：English Publisher：Clinica Chimica Acta

Introduction The protective effects of vascular endothelial growth factor (VEGF)-A165b on kidney tissue have been suggested in animal studies. However, the relevance of urinary and circulating VEGF-A165b levels in chronic kidney disease patients remains unclear. Therefore, the present study aimed to investigate the urinary and circulating VEGF-A165b levels in patients with chronic kidney disease. Methods This observational study enrolled a total of 92 Japanese patients with chronic kidney disease, who had undergone inulin renal clearance measurements for the accurate assessment of measured GFR. Urinary or circulating total VEGF-A and VEGF-A165b levels were measured using enzyme-linked immunosorbent assay. Results Urinary VEGF-A165b levels were significantly lower in G3a, G3b, and G4 + G5 category patients than in G1 + G2 category patients. Correlation analysis found that serum creatinine levels, serum cystatin C levels, eGFRcre, eGFRcys, and mGFR were weakly but significantly correlated with urinary VEGF-A165b levels. Additionally, circulating VEGF-A165b levels were significantly higher in G4 + G5 category patients than in G1 + G2 category patients. Conclusion A low urinary VEGF-A165b level reflects renal dysfunction in the chronic kidney disease stage, while a high circulating VEGF-A165b level cannot be attributed to decreased renal clearance.

DOI： 10.1016/j.cca.2017.10.014

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients

Kaihan, AB; Yasuda, Y; Katsuno, T; Kato, S; Imaizumi, T; Ozeki, T; Hishida, M; Nagata, T; Ando, M; Tsuboi, N; Maruyama, S

CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 21 ( 6 ) page： 986 - 994 2017.12

Language：English Publisher：Clinical and Experimental Nephrology

Background: The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). Methods: A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. Results: In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. Conclusions: The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

DOI： 10.1007/s10157-017-1393-x

Seasonal proteinuria changes in IgA nephropathy patients after proteinuria remission

Inagaki, K; Yasuda, Y; Ando, M; Kaihan, AB; Hachiya, A; Ozeki, T; Hishida, M; Imaizumi, T; Katsuno, T; Kato, S; Tsuboi, N; Maruyama, S

PLOS ONE Vol. 12 ( 11 ) page： e0187607 2017.11

Language：English Publisher：PLoS ONE

Background: Proteinuria is a powerful prognostic factor for end-stage renal disease in IgA nephropathy (IgAN) patients. However, it is not known whether proteinuria exacerbations are related to seasonal changes. Methods: We retrospectively enrolled consecutive patients diagnosed with IgAN by kidney biopsy at our hospital between 2002 and 2014. Proteinuria remission was defined as urinary protein <0.3 g/gCr in two consecutive outpatient urinalyses and exacerbation as urinary protein 0.75 g/gCr. Four seasons were defined: spring (March–May), summer (June–August), autumn (September–November), and winter (December–February). We performed a multivariate analysis to identify factors associated with the second remission following a proteinuria exacerbation. Results: We analyzed 116 patients. Proteinuria remission and exacerbation occurred in 77, and 43 patients, respectively. The incidence of proteinuria exacerbation was significantly higher in autumn and winter than in spring and summer (p = 0.040). The cumulative second remission rate was significantly higher in patients with autumn and winter proteinuria exacerbation than in patients with spring and summer exacerbations (p = 0.0091). In multivariate analyses, exacerbation onset in autumn and winter (hazard ratio [HR], 3.51; 95% confidence interval [CI], 1.41–8.74) and intensive therapy (HR, 2.26; 95% CI, 1.05–4.88) were significantly associated with a second proteinuria remission. Conclusion: In IgAN patients in proteinuria remission, proteinuria exacerbation frequently occurred in autumn and winter. Exacerbations occurring in autumn and winter tended to remit early.

DOI： 10.1371/journal.pone.0187607

Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers

Kubo, Y; Imaizumi, T; Ando, M; Nakatochi, M; Yasuda, Y; Honda, H; Kuwatsuka, Y; Kato, S; Kikuchi, K; Kondo, T; Iwata, M; Nakashima, T; Yasui, H; Takamatsu, H; Okajima, H; Yoshida, Y; Maruyama, S

PLOS ONE Vol. 12 ( 10 ) page： e0185476 2017.10

Language：English Publisher：PLoS ONE

Background: Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD. Methods: We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated. Results: In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09–1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively). Conclusions: After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

DOI： 10.1371/journal.pone.0185476

The association between intensive care unit-acquired hypernatraemia and mortality in critically ill patients with cerebrovascular diseases: a single-centre cohort study in Japan

Imaizumi, T; Nakatochi, M; Fujita, Y; Nomura, R; Watanabe, K; Maekawa, M; Yamakawa, T; Katsuno, T; Maruyannal, S

BMJ OPEN Vol. 7 ( 8 ) page： e016248 2017.8

Language：English Publisher：BMJ Open

Objectives: Hypernatraemia is one of the major electrolyte disorders associated with mortality among critically ill patients in intensive care units (ICUs). It is unclear whether this applies to patients with cerebrovascular diseases in whom high sodium concentrations may be allowed in order to prevent cerebral oedema. This study aimed to examine the association between ICU-acquired hypernatraemia and the prognosis of patients with cerebrovascular diseases. Design: A retrospective cohort study. Setting: The incidence of ICU-acquired hypernatraemia was assessed retrospectively in a single tertiary care facility in Japan. Participants: Adult patients (≥18 years old) whose length of stay in ICU was >2 days and those whose serum sodium concentrations were 130-149 mEq/L on admission to ICU were included. Outcome measures: 28-day in-hospital mortality risk was assessed by Cox regression analysis. Hypernatraemia was defined as serum sodium concentration ≥150 mEq/L. Using multivariate analysis, we examined whether ICU-acquired hypernatraemia and the main symptom present at ICU admission were associated with time to death among ICU patients. We also evaluated how the maximum and minimum sodium concentrations during ICU stay were associated with mortality, using restricted cubic splines. Results: Of 1756 patients, 121 developed ICU-acquired hypernatraemia. Multivariate Cox proportional hazard analysis revealed an association between ICU-acquired hypernatraemia and 28-day mortality (adjusted HR, 3.07 (95% CI 2.12 to 4.44)). The interaction between ICU-acquired hypernatraemia and cerebrovascular disease was significantly associated with 28-day mortality (HR, 3.03 (95% CI 1.29 to 7.15)). The restricted cubic splines analysis of maximum serum sodium concentration in ICU patients determined a threshold maximum of 147 mEq/L. There was no significant association between minimum sodium concentration and mortality. Conclusions: ICU-acquired hypernatraemia was associated with an increased mortality rate among critically ill patients with cerebrovascular diseases; the threshold maximum serum sodium concentration associated with mortality was 147 mEq/L.

DOI： 10.1136/bmjopen-2017-016248

Association Between <i>Staphylococcus aureus</i> Bacteremia and Hospital Mortality in Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From Japanese Tertiary Care Centers

Imaizumi, T; Hasegawa, T; Nomura, A; Sasaki, S; Nishiwaki, H; Ozeki, T; Shimizu, H; Minatoguchi, S; Yamakawa, T; Yazawa, M; Uchida, D; Kawarazaki, H; Miyamoto, M; Suzuki, T; Koitabashi, K; Furusho, M; Fujita, Y

THERAPEUTIC APHERESIS AND DIALYSIS Vol. 21 ( 4 ) page： 354 - 360 2017.8

Language：English Publisher：Therapeutic Apheresis and Dialysis

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non-SAB cases. Hospital mortality was higher among SAB cases than non-SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

DOI： 10.1111/1744-9987.12534

Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers

Imaizumi, T; Ando, M; Nakatochi, M; Maruyama, S; Yasuda, Y; Honda, H; Kuwatsuka, Y; Kato, S; Kondo, T; Iwata, M; Nakashima, T; Yasui, H; Takamatsu, H; Okajima, H; Yoshida, Y; Matsuo, S

CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 21 ( 3 ) page： 457 - 464 2017.6

Language：English Publisher：Clinical and Experimental Nephrology

Background: Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). Methods: This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. Results: BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). Conclusion: The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

DOI： 10.1007/s10157-016-1315-3

Development and Validation of a Clinical Prediction Rule for Bacteremia among Maintenance Hemodialysis Patients in Outpatient Settings

Sasaki, S; Hasegawa, T; Kawarazaki, H; Nomura, A; Uchida, D; Imaizumi, T; Furusho, M; Nishiwaki, H; Fukuma, S; Shibagaki, Y; Fukuhara, S

PLOS ONE Vol. 12 ( 1 ) page： e0169975 2017.1

Language：English Publisher：PLoS ONE

Background To our knowledge, no reliable clinical prediction rule (CPR) for identifying bacteremia in hemodialysis (HD) patients has been established. The aim of this study was to develop a CPR for bacteremia in maintenance HD patients visiting the outpatient department. Methods This multicenter cohort study involved consecutive maintenance HD patients who visited the outpatient clinic or emergency room of seven Japanese institutions between August 2011 and July 2013. The outcome measure was bacteremia diagnosed based on the results of blood cultures. The candidate predictors for bacteremia were extracted through a literature review. A CPR for bacteremia was developed using a coefficient-based multivariable logistic regression scoring method, and calibration was performed. The test performance was then assessed for the CPR. Results Of 507 patients eligible for the study, we analyzed the 293 with a complete dataset for candidate predictors. Of these 293 patients, 48 (16.4%) were diagnosed with bacteremia. At the conclusion of the deviation process, body temperature ô 38.3°t rate ô 125 /min, C-reactive protein ô 10 mg/dL, alkaline phosphatase >360 IU/L, and no prior antibiotics use within the past week were retained and scored. The CPR had a good fit for the model on calibration. The AUC of the CPR was 0.76, and for score CPR ô 2, the sensitivity and specificity were 89.6% and 51.4%, respectively. Conclusions We established a simple CPR for bacteremia in maintenance HD patients using routinely obtained clinical information in an outpatient setting. This model may facilitate more appropriate clinical decision making.

DOI： 10.1371/journal.pone.0169975