Kenjiro Honda

The University of Tokyo, Tōkyō, Japan

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Publications (14)32.3 Total impact

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    ABSTRACT: Type 2 diabetes mellitus is a leading health issue worldwide. Among cases of diabetes mellitus nephropathy (DN), the major complication of type 2 diabetes mellitus, the nephrotic phenotype is often intractable to clinical intervention and demonstrates the rapid decline of renal function to end-stage renal disease. We recently identified the gene for glypican-5 (GPC5), a cell-surface heparan sulfate proteoglycan, as conferring susceptibility for acquired nephrotic syndrome and additionally identified an association through a genome-wide association study between a variant in GPC5 and DN of type 2 diabetes mellitus. In vivo and in vitro data showed a progressive increase of GPC5 in type 2 DN along with severity; the excess was derived from glomerular mesangial cells. In this study, diabetic kidney showed that accumulation of fibroblast growth factor (Fgf)2 strikingly induced progressive proteinuria that was avoided in Gpc5 knockdown mice. The efficacy of Gpc5 inhibition was exerted through expression of the Fgf receptors 3 and 4 provoked in the diabetic kidney attributively. Extraglomerular Fgf2 was pathogenic in DN, and Gpc5 effectively inhibited the glomerular accumulation of Fgf2, the subsequent increase of mesangial extracellular matrix, and the podocytes' small GTPase activity. These findings elucidate the pivotal role of GPC5, identified as a susceptible gene in the genome-wide association study, in hyperglycemia-induced glomerulopathy. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
    American Journal Of Pathology 05/2015; DOI:10.1016/j.ajpath.2015.03.025 · 4.60 Impact Factor
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    ABSTRACT: Fabry disease is a genetic disorder caused by deficient activity of lysosomal enzyme α-galactosidase A (GLA) and end-stage renal disease (ESRD) will be present after accumulation of glycosphingolipids within the kidney. Undiagnosed atypical variants of Fabry disease, which are limited to renal involvement, were found in several ESRD patient populations. On the other hand, unexpectedly high frequencies of male subjects having the c.196G>C nucleotide change (p.E66Q) showing low α-GLA activity have been reported on Japanese and Korean screening for Fabry disease. However, several evidences indicate the c.196G>C is not a pathogenic mutation but is a functional polymorphism. In the present study, high-throughput screening of serum GLA could successfully indentify two Fabry disease patients in a cohort consisted of 1080 male hemodialysis patients. Moreover, our serum assay was able to distinguish two patients with disease-causing genetic mutations (p.G195V and p.M296I) from eight functional variants that showed relatively decreased enzyme activity (p.E66Q). In conclusion, high-throughput serum enzyme assay distinctly identified disease-causing mutants and functional variants of GLA gene in Japanese male hemodialysis patients. In addition, our results underscore the high prevalence of not only undiagnosed Fabry patients but functional variants of p.E66Q among the ESRD population.
    Journal of Human Genetics 06/2012; 57(9):575-9. DOI:10.1038/jhg.2012.68 · 2.53 Impact Factor
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    ABSTRACT: Atherosclerotic complications have a significant effect on mortality in patients undergoing hemodialysis (HD) therapy. However, anti-atherosclerotic and cardioprotective effects of on-line hemodiafiltration (HDF) remain to be elucidated. We prospectively compared the anti-atherosclerotic and cardioprotective effects in two randomly divided groups, i.e. on-line HDF group (n = 13) and conventional HD group (n = 9) for 1 year. Surrogate markers were brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT) of carotid artery as an atherosclerosis marker, and cardiac functional surrogate markers included left ventricular mass index (LVMI), ejection fraction (EF), and LV diastolic capacity represented as E/A and deceleration time (DT). LVMI in on-line HDF patients showed significant regression after 1 year of treatment (131.9 ± 25.8 to 116.5 ± 24.7 g/m(2), P = 0.03), while LVMI in HD patients did not show any significant change (148.0 ± 47.1 to 142.3 ± 35.5 g/m(2)). Levels of baPWV in HD patients showed a significant increase (11.4%) from basal levels, while on-line HDF groups showed no significant increase. Furthermore, HD patients showed significant worsening of LV diastolic capacity (E/A: from 0.87 ± 0.12 to 0.79 ± 0.08, P = 0.03), while it was not shown in on-line HDF patients. Ejection fraction and IMT did not show any significant change in both groups. Serum albumin, C-reactive protein, β2 microglobulin, blood pressure, and anti-hypertensive drug use did not change in both groups. On-line HDF showed a significant improvement in LVMI and prevented a significant worsening of baPWV or LV diastolic capacity compared with patients on conventional HD therapy.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2012; 16(2):181-8. DOI:10.1111/j.1744-9987.2011.01042.x · 1.53 Impact Factor
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    ABSTRACT: Urinary L-type fatty acid-binding protein (L-FABP) has not been evaluated for adult post-cardiac surgery acute kidney injury (AKI) to date. This study was undertaken to evaluate a biomarker panel consisting of urinary L-FABP and N-acetyl-β-D-glucosaminidase (NAG), a more established urinary marker of kidney injury, for AKI diagnosis in adult post-cardiac surgery patients. This study prospectively evaluated 77 adult patients who underwent cardiac surgery at 2 general hospitals. Urinary L-FABP and NAG were measured before surgery, at intensive care unit arrival after surgery (0 hours), 4, and 12 hours after arrival. The AKI was diagnosed by the Acute Kidney Injury Network criteria. Of 77 patients, 28 patients (36.4%) developed AKI after surgery. Urinary L-FABP and NAG were significantly increased. However, receiver operating characteristic (ROC) analysis revealed that the biomarkers' performance was statistically significant but limited for clinical translation (area under the curve of ROC [AUC-ROC] for L-FABP at 4 hours 0.72 and NAG 0.75). Urinary L-FABP showed high sensitivity and NAG detected AKI with high specificity. Therefore, we combined these 2 biomarkers, which revealed that this combination panel can detect AKI with higher accuracy than either biomarker measurement alone (AUC-ROC 0.81). Moreover, this biomarker panel improved AKI risk prediction significantly compared with predictions made using the clinical model alone. When urinary L-FABP and NAG are combined, they can detect AKI adequately, even in a heterogeneous population of adult post-cardiac surgery AKI. Combining 2 markers with different sensitivity and specificity presents a reasonable strategy to improve the diagnostic performance of biomarkers.
    The Annals of thoracic surgery 02/2012; 93(2):577-83. DOI:10.1016/j.athoracsur.2011.10.048 · 3.65 Impact Factor
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    ABSTRACT: Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy.
    AJP Cell Physiology 08/2011; 301(6):C1423-30. DOI:10.1152/ajpcell.00065.2011 · 3.67 Impact Factor
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    Kenjiro Honda · Sumi Hidaka · Shuzo Kobayashi
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2011; 15(2):215-7. DOI:10.1111/j.1744-9987.2010.00904.x · 1.53 Impact Factor
  • Nihon Toseki Igakkai Zasshi 01/2011; 44(5):455-461. DOI:10.4009/jsdt.44.455
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    ABSTRACT: Beraprost sodium (BPS) is a stable, orally active prostaglandin I(2) (PGI(2) ) analog with antiplatelet and vasodilating properties. It has been reported that PGI(2) has pleiotropic effects that are anti-inflammatory and anti-atherogenic. In this study, we aim to determine the relationship between PGI(2) and renal anemia. We conducted a prospective randomized trial including 20 hemodialysis patients. Ten patients were assigned to be treated with 120 µg/day of BPS and the other patients were assigned to a control group. After six months, the titer of hemoglobin had significantly increased in the BPS group compared to the baseline (11.1 ± 0.3 g/dL vs. 10.3 ± 1.4 g/dL, respectively), and there was a significant difference between the BPS group and the control group. The level of ferritin was lower in the BPS group compared to the control group, but the average dose of erythropoietin did not significantly change. These findings suggest that BPS may improve renal anemia in hemodialysis patients.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 10/2010; 14(5):472-6. DOI:10.1111/j.1744-9987.2010.00814.x · 1.53 Impact Factor
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    ABSTRACT: Increased prevalence of aortic and mitral valve calcification has been reported in patients on hemodialysis, but it remains unknown whether aortic and mitral valve calcification arise from similar pathogenesis. We detected heart valve calcification using two-dimensional echocardiography, and we related valve calcification to various clinical parameters in patients treated with hemodialysis three times a week for more than 1 year. In 112 patients (77 men and 35 women, age 67+/-10 years, duration on hemodialysis 95+/-67 months), aortic and mitral valve calcification were observed in 84 (75.0%) and 58 (51.7%) patients, respectively. Aortic valve calcification was associated with increased age, higher serum calcium, lower serum albumin, lower total cholesterol and higher high-sensitivity C-reactive protein. Multivariate analysis showed that increased age and higher serum calcium were independently associated with aortic valve calcification. Conversely, mitral valve calcification was associated with increased age, higher high-sensitivity C-reactive protein and higher serum beta(2)-microglobulin, but not with higher serum calcium. In multivariate analysis, increased age and higher serum beta(2)-microglobulin were independently associated with mitral valve calcification. Serum beta(2)-microglobulin was associated with longer duration on hemodialysis, malnutrition inflammation (lower serum albumin and higher high-sensitivity C-reactive protein) and dyslipidemia. Considering the results in previous studies showing that the distribution of beta(2)-microglobulin amyloid deposition was consistent with that of tissue calcification in patients on hemodialysis, beta(2)-microglobulin may have pathogenic roles in valve calcification.
    Hypertension Research 04/2010; 33(6):622-6. DOI:10.1038/hr.2010.44 · 2.94 Impact Factor
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    ABSTRACT: The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all-cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron-beam computed tomography. Fifty-six patients underwent a second electron-beam computed tomography after a 15-month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross-sectional study, HD vintage and high-sensitive C-reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan-Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all-cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15-month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all-cause deaths.
    Hemodialysis International 03/2010; 14(2):218-25. DOI:10.1111/j.1542-4758.2009.00423.x · 1.36 Impact Factor
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    ABSTRACT: Hypertension has an important function in the formation of renal arterio-arteriolosclerosis. However, renal arterio-arteriolosclerosis is sometimes found in biopsy specimens of normotensive patients, which indicates unknown factors may contribute to renal arterio-arteriolosclerosis. In this study, we aimed to evaluate the effects of glucose metabolism/insulin resistance on renal arterio-arteriolosclerosis. Forty-eight patients with biopsy-proven non-diabetic chronic glomerular disease were included. Renal arterio-arteriolosclerosis was evaluated as the percentage of vessels showing hyaline changes or wall thickening. We correlated renal arterio-arteriolosclerosis with clinical parameters including indices obtained by 75 g oral glucose tolerance test. Of the 48 patients, 30 had hypertension. The results of univariate analysis showed significant association of renal arterio-arteriolosclerosis with hypertension, increased serum creatinine (S-Cr), hypertriglyceridemia, increased 2-h plasma glucose (PG) and increased 2-h plasma insulin (PI). In stepwise multiple regression analysis, hypertension (beta=0.344, P=0.009), S-Cr (beta=0.287, P=0.03) and 2-h PG (beta=0.274, P=0.03) were independently associated with renal arterio-arteriolosclerosis. Eleven of the 30 hypertensive patients did not have renal arterio-arteriolosclerosis. The hypertensive patients with renal arterio-arteriolosclerosis showed significantly higher 2-h PG (134+/-25 vs. 106+/-26 mg per 100 ml, P=0.008) and higher 2-h PI (67.7+/-34.9 vs. 48.3+/-30.0 microU ml(-1), P=0.04) compared with those without renal arterio-arteriolosclerosis, but the difference in S-Cr was not significant. Postprandial hyperglycemia and hyperinsulinemia may contribute to the formation of renal arterio-arteriolosclerosis independently of hypertension.
    Hypertension Research 02/2010; 33(5):499-504. DOI:10.1038/hr.2010.22 · 2.94 Impact Factor
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    ABSTRACT: Heart valve calcification is an important predictor for all-cause and cardiovascular mortality in hemodialysis patients. Recently, serum beta(2)-microglobulin has been associated with cardiovascular disease in the non-hemodialysis population, but the relationship between serum beta(2)-microglobulin and valve calcification remains unknown. In this cross-sectional study, we recorded the patients' clinical parameters, including serum beta(2)-microglobulin, and related these parameters to the number of calcified valves detected by echocardiography. The patients included 80 males and 35 females (age 67 +/- 10 years; duration on hemodialysis 96 +/- 67 months). Calcification of the aortic and mitral valves was observed in 89 (77.4%) and 59 patients (51.3%), respectively. Fifty-one patients (44.3%) showed calcification of both valves. In univariate analysis, age (r = 0.301, P = 0.001), serum albumin (r = -0.219, P = 0.01), calcium (r = 0.205, P = 0.02), high sensitivity C-reactive protein (r = 0.209, P = 0.02), and beta(2)-microglobulin (r = 0.206, P = 0.02) significantly correlated with the number of calcified valves. Stepwise multiple regression analysis showed that age (beta = 0.389, P < 0.001) and calcium (beta = 0.223, P = 0.01) were independent determinants for valve calcification (r(2) = 0.195). In addition, carotid intima media thickness was significantly higher in patients with valve calcification compared with those without valve calcification. Our results suggested the impacts of calcium metabolism and malnutrition-inflammation complex syndrome on valve calcification. In addition, serum beta(2)-microglobulin may be another potential marker of cardiovascular complications in patients on hemodialysis.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 12/2008; 12(6):464-8. DOI:10.1111/j.1744-9987.2008.00636.x · 1.53 Impact Factor
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    ABSTRACT: Soybean dwarf virus (SbDV) is divided into four strains, namely YS, YP, DS and DP. YS and YP cause yellowing in soybeans, while DS and DP cause dwarfing. YS and DS are transmitted by Aulacorthum solani, while YP and DP are transmitted by Acyrthosiphon pisum. To clarify the taxonomic relationship between the four strains and to classify SbDV into an appropriate genus in the Luteoviridae, we determined the complete nucleotide sequences of genomic RNAs of four isolates belonging to each of the strains. The genomes of the four isolates had a chimeric form between Barley yellow dwarf virus-PAV and poleroviruses, and the genome organizations were similar to the Australian isolate SbDV Tas-1. In all of the non-coding regions and ORFs, nucleotide and deduced amino acid sequence identity between the same symptom-type strains was higher than that between the different symptom-type strains. However, in the N-terminal half of the readthrough domain (RTD) the deduced amino acid identity between the same aphid transmissibility-type strains was higher than that between the different aphid transmissibility-type strains. These data suggest that the N-terminal half of the RTD is closely related to the aphid transmission specificity, and that the present strains were generated from ancestral Y and D strains by mutations and strong selection pressures of efficient aphid transmission. Therefore, we propose that SbDV should be classified into a new genus in the family Luteoviridae and that the four strains described should be regarded as different strains of the same virus, rather than as distinct virus species.
    Archives of Virology 11/2001; 146(10):1885-98. DOI:10.1007/s007050170040 · 2.28 Impact Factor
  • Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 29(5):583-5. · 2.20 Impact Factor

Publication Stats

112 Citations
32.30 Total Impact Points


  • 2012–2015
    • The University of Tokyo
      • Department of Nephrology and Endocrinology
      Tōkyō, Japan
  • 2008–2012
    • Shonan Kamakura General Hospital
      Kamakura, Kanagawa, Japan
  • 2001
    • National Agriculture and Food Research Organization
      Tsukuba, Ibaraki, Japan