Kenjiro Yamakawa

Shirasagi Hospital, Ōsaka, Ōsaka, Japan

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Publications (14)39.12 Total impact

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    ABSTRACT: Background/aims: Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients. Methods: Hand roentgenography of 167 male maintenance hemodialysis patients was conducted, and visible vascular calcification of the hand arteries was evaluated. Serum levels of 3 bone formation markers (BAP, osteocalcin, and N-terminal propeptide of type I collagen) and 2 bone resorption markers (C-terminal telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured, along with serum intact parathyroid hormone (PTH). Results: Of 167 patients, visible vascular calcification was seen in 37 patients. Among the bone formation and resorption markers, serum BAP was significantly higher in patients with vascular calcification than in those without (p<0.05); although the other 5 serum bone markers were not significantly different between them. Multivariate logistic regression analyses revealed that log [BAP] was significantly associated with vascular calcification after adjustment for age, hemodialysis duration, presence of diabetes, log [intact PTH] and each of the other 5 bone markers (p<0.0001). Conclusions: Higher serum BAP, but not other bone markers, is significantly associated with the presence of vascular calcification in male hemodialysis patients.
    No preview · Article · Sep 2014 · Kidney and Blood Pressure Research
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    ABSTRACT: Background/aims: Serum magnesium (Mg) levels have been associated with muscle performance in the general population. We hypothesized that serum Mg would be associated with muscle quality in hemodialysis patients. Methods: A total of 310 patients were examined (age: 58 ± 12 years, hemodialysis duration: 6.4 ± 6.0 years, 60.6% men, and 36.1% diabetics). Arm lean mass was measured by dual energy X-ray absorptiometry (DXA) on the dominant side. Arm muscle quality was defined as the ratio of the handgrip strength to the arm lean mass of the same side (kg/kg). Results: Serum Mg was 1.15 ± 0.16 mmol/L (2.8 ± 0.4 mg/dL), being higher than the reference range of normal subjects. There was a significant negative correlation between muscle quality and age (r = -0.326, p<0.0001) and duration of hemodialysis (r = -0.253, p<0.0001). The muscle quality of the diabetics was significantly lower than that of the non-diabetics (p<0.001). There was a significant, positive correlation between muscle quality and serum Mg (r = 0.118, p<0.05), but not serum calcium or phosphate. In multiple regression analysis, age, gender, hemodialysis duration, diabetes, and serum Mg (β = 0.129, p<0.05) were significantly and independently associated with muscle quality (R(2) = 0.298, p<0.0001). Conclusion: These results demonstrated that a lower serum Mg concentration was significantly associated with poor muscle quality in hemodialysis patients. Further studies are needed to explore the mechanism by which lower serum Mg affects muscle quality.
    No preview · Article · Feb 2014 · Magnesium research: official organ of the International Society for the Development of Research on Magnesium
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    ABSTRACT: No studies have reported the pharmacokinetics of tazobactam/ piperacillin(TAZ/PIPC), a penicillin antibiotic combined with a β-lactamase inhibitor at a TAZ/PIPC ratio of 1: 8, in Japanese patients with chronic kidney disease on hemodialysis(HD). We intravenously injected a TAZ/PIPC dose of 4.5 g over a 30-min period every 12 h (4.5 g twice daily) to five HD patients diagnosed as having pneumonia or suspected sepsis (one male, four females; mean [± SD] age, 73.2 [9.3] years; mean [± SD] body weight, 46.2 [10.3] kg), and analyzed the pharmacokinetics of TAZ and PIPC using the one-compartment model. Based on the results of the analysis, the proportion of the time during which the plasma PIPC concentration (total concentration, free concentration) was maintained above the minimum inhibitory concentration(MIC) (time above MIC; %TAM) was calculated. The maximum concentrations (Cmax) of TAZ and PIPC after the first administration were 37.5 ± 9.3 and 386 ± 121 μ g/mL, respectively. The Cmax values of TAZ and PIPC after repeated administration (4 to 6 days) were 85.1 ± 16.4 and 824 ± 260 μ g/mL, respectively, which were both higher than the Cmax after the first administration. The half-lives (T1/2) of TAZ and PIPC were 14.8 ± 5.5 and 10.0 ± 4.1 h, respectively, indicating a markedly delayed elimination compared to individuals with normal renal function. The rate of reduction in plasma concentrations before and after HD was high at 84.0 ± 4.5% for TAZ and 85.4 ± 4.3% for PIPC. Based on the finding that the MIC allowing % TAM exceeding 50% was 64 μ g/mL in the four patients in whom pharmacokinetics could be assessed, and taking into consideration the Cmax at which tolerability has been confirmed in other studies, administration of TAZ/PIPC at 4.5 g once daily or 2.25 g twice daily was proposed as an appropriate dose for HD patients. Moreover, with the exception of one patient for whom an assessment could not be made, treatment was effective in the other four patients, and no side effects were observed.
    No preview · Article · Sep 2013
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    ABSTRACT: Background: It has been reported that there is a significant positive relationship between PTH and body weight or body mass index in the general population. However, little is known about this relationship in dialysis patients in whom PTH levels are higher. It is also not known whether fat mass or lean mass is associated with serum PTH among these patients. In the present study, we examined the association of intact PTH with fat mass and lean mass in hemodialysis patients. Methods: Serum intact PTH, calcium, and phosphate were measured in 590 hemodialysis patients (age, 60.2 ± 12.2 y; median hemodialysis duration, 59.6 mo; 343 males and 247 females; diabetics, 27.7%). Fat mass and lean mass were measured by dual-energy x-ray absorptiometry. Results: Intact PTH correlated significantly and positively with body weight and body mass index in all patients. Intact PTH correlated significantly and positively with fat mass and lean mass in males (P < .01), and tended to correlate positively with fat mass and lean mass in females (P < .1). In multiple regression analyses after adjustment for age, gender, hemodialysis duration, calcium, phosphate, vitamin D use, and phosphate binder use, intact PTH was associated significantly with body weight (β = .190; P < .0001), body mass index (β = .177; P < .0001), fat mass (β = .142; P < .0005), and lean mass (β = .192; P < .01). Furthermore, intact PTH was associated significantly and independently with both fat mass and lean mass after adjustment (R(2) = .206; P < .0001). Conclusion: Serum intact PTH in chronic hemodialysis patients is associated significantly and positively with body composition of fat mass and lean mass.
    No preview · Article · Feb 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis in transformed cells. In addition to tumor surveillance, recent findings suggest that TRAIL and its receptor system have a protective role against infection and cardiovascular disease (CVD). Patients undergoing hemodialysis have a high mortality rate with a unique risk factor profile. Considering that the leading causes of death in these patients are infection and CVD, TRAIL represents an attractive candidate for predicting mortality in this population. We therefore investigated whether TRAIL predicted mortality in hemodialysis patients. Methods: The study was a retrospective observational cohort design of 45-month duration in 149 male hemodialysis patients. The subjects were divided into two groups according to their baseline TRAIL level measured by ELISA (low or high TRAIL group). The main outcome was all-cause mortality. Results: During the follow-up period, 33 patients died, mostly because of CVD (n=11) or infection (n=9). Crude survival analyses showed that a low TRAIL level was a powerful predictor of all-cause (p=0.011) and infectious mortality (p=0.048). The predictive power of TRAIL remained after adjustment for various confounding factors. Conclusions: The serum TRAIL level may be a novel biomarker for predicting prognosis in hemodialysis patients.
    No preview · Article · Feb 2013 · Cytokine

  • No preview · Article · Dec 2012 · Nihon Naika Gakkai Zasshi
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    ABSTRACT: Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism. Introduction Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism. Methods Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined. Results ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = −0.303, p < 0.0001), hemoglobin A1C (ρ = −0.214, p < 0.01), and glycated albumin (ρ = −0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH]. Conclusion Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.
    No preview · Article · May 2012 · Osteoporosis International
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    ABSTRACT: Background/Aim: Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. Methods: The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. Results: The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from -0.023 ± 0.029 g/cm2/year to -0.002 ± 0.033 g/cm2/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. Conclusion: There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.
    No preview · Article · Oct 2011 · Clinical nephrology
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    ABSTRACT: Bone mineral density of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin. There was a significant positive correlation between serum adiponectin and serum NTX. Thus, adiponectin may play a role in mineral and bone disorder in chronic kidney disease stage 5 dialysis (CKD 5D) patients. Serum adiponectin, an adipocyte-produced hormone, has been reported to correlate negatively with bone mineral density (BMD) in the general population. However, little is known about the association between adiponectin and BMD in patients with CKD. BMD of the 1/3 distal and ultra-distal radius, which are enriched with cortical and cancellous bone, respectively, and the lumbar spine was measured by dual X-ray absorptiometry in 114 Japanese male hemodialysis patients (age 61.0 ± 11.1 years; hemodialysis duration 6.6 ± 3.0 years; 43.9% diabetics). Serum total adiponectin, bone formation marker (bone alkaline phosphatase, BAP), and bone resorption marker (cross-linked N-telopeptide of type I collagen (NTX)) were measured. The BMD of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin level (r = -0.229, p = 0.014; r = -0.286, p = 0.002; r = -0.227, p = 0.013, respectively). In multiple linear regression analyses, serum adiponectin was significantly and independently associated with the BMD of the 1/3 distal radius (R(2) = 0.173, p < 0.001) and ultra-distal radius (R(2) = 0.278, p < 0.001) after adjustment of age, hemodialysis duration, body weight, %fat mass, and log [intact PTH], although it was not with the BMD of the lumbar spine. There was a significant positive correlation between serum adiponectin and serum NTX (r = 0.321, p < 0.001), although there was no significant correlation between serum adiponectin and serum BAP. Increased levels of serum adiponectin were associated with decrease in BMD in male hemodialysis patients. Adiponectin may play a role in mineral and bone disorder, possibly in bone resorption, of patients with CKD 5D.
    No preview · Article · Sep 2011 · Osteoporosis International
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    ABSTRACT: INTRODUCTION AND AIMS: Uremia is believed to accelerate the aging process due to its effects on atherosclerosis, oxidant stress, arterial calcification, and other mechanisms. We therefore hypothesized that, beyond the period of clinical instability soon after starting dialysis, the rate of dying from any cause increases with years on dialysis (vintage), and we examined whether this association varies by age. METHODS: Census data were obtained from all HD patients at each participating facility in 12 countries in DOPPS 2 (2002-2004; 48,571 patients; 332 facilities) and DOPPS 3 (2005-2008; 43,513 patients; 323 facilities). Cox regression was used to estimate hazard ratios (HR) comparing categories of dialysis vintage within each patient subgroup based on age at study enrollment. HRs were adjusted for sex, race and diabetes as the cause of ESRD, as well as age as a time-dependent covariate. Models were stratified by region and study phase, and accounted for within-facility clustering of the outcome. RESULTS: There was little association between dialysis vintage and the all-cause mortality rate among patients <45 years of age at baseline (see Figure). For older patients, the vintage-mortality association was U-shaped: mortality was higher at vintage ≤4 months and >3 years compared to vintage 4 months to 3 years. The results were similar in analyses excluding patients with prior kidney transplant. CONCLUSIONS: The estimated effect of dialysis vintage on mortality in the DOPPS varies with age at study enrollment. As hypothesized, mortality beyond the initial dialysis period increases monotonically with vintage, but only for patients ≥45 years old. This difference may be due to the fact that, compared to younger patients, older patients are less able to tolerate the impact of initiation of HD in the first few months, as well as the cumulative effects of uremia (or the dialysis treatment) after years of dialysis. View larger version: In this window In a new window Download as PowerPoint Slide
    No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
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    ABSTRACT: We present two cases of markedly decreased serum aprindine levels during anti-tuberculous therapy.Case 1 was a 65year-old man with end-stage renal disease (ESRD) on regular dialysis who was being treated for atrial fibrillation with oral aprindine (40 mg/day).In the 6-month period before treatment with anti-tuberculous drugs,the mean serum aprindine concentration had been 1.01 (SD 0.31)μg/mL (n=6).When anti-tuberculous therapy including rifampicin was commenced for intestinal tuberculosis,there was a marked decrease in the serum aprindine concentration to 0.14μg/mL but after it was discontinued,the serum aprindine concentration rose to 0.48μg/mL.Case 2 was a 76-year-old man with ESRD on regular dialysis who was being treated for paroxysmal atrial fibrillation with oral aprindine (30 mg/day).In the 9-month period before anti-tuberculous therapy,the mean serum aprindine concentration had been 0.67 (SD 0.16)μg/mL (n=9).Anti-tuberculous therapy including rifampicin for soft-tissue tuberculosis of the left arm resulted in a marked decrease in the serum aprindine concentration to 0.09μg/mL.Aprindine is known to be metabolized by cytochrome P 450 (CYP) 2D6 and CYP3A4 and rifampicin is a potent inducer of CYP3A4 but has little effect on CYP2D6.Accordingly,the coadministration of rifampicin is assumed to have caused the substantial decreases in serum aprindine concentrations,probably through the induction of CYP3A4.Concomitant administration with rifampicin may therefore result in the failure of aprindine to ameliorate arrhythmia.
    No preview · Article · Jan 2008
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    ABSTRACT: Vascular endothelial growth factor (VEGF), expressed in a variety of mesenchymal cells including vascular smooth muscle cells (VSMC), is a potent mitogen for endothelial cells, and is used clinically applied for ischemic disease of peripheral vessels. To determine whether peroxisome proliferator-activated receptor gamma (PPARgamma) regulates VEGF production in VSMC, we examined VEGF secretion from VSMC treated with PPAR agonists. Troglitazone increased VEGF secretion in a time- and dose-dependent manner (261 +/- 35% with 25 mM of troglitazone for 24 h), and also increased levels of VEGF mRNA. VEGF secretion was also increased by other PPARgamma agonists, pioglitazone, LY171883, and 15d-PGJ2 (224 +/- 17.1%, 247 +/- 36.8% and 171 +/- 7.8%, respectively), but not the PPARgamma agonists bezafibrate and Wy14643 (85.2 +/- 1.5%, 94.6 +/- 3.2, respectively). Our findings suggest that thiazolidinediones might be useful for the therapeutic angiogenesis for ischemic artery disease.
    No preview · Article · Jun 2000 · Biochemical and Biophysical Research Communications
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    S Fukumoto · H Koyama · M Hosoi · K Yamakawa · S Tanaka · H Morii · Y Nishizawa
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    ABSTRACT: cAMP and cGMP are known to suppress vascular smooth muscle cell (SMC) proliferation. In this study, our aim was to delineate the molecular mechanism underlying cAMP and cGMP suppression of cell cycle transition in human SMCs. cAMP inhibits both platelet-derived growth factor-stimulated cyclin-dependent kinase (cdk) 2 and cdk4 activation through upregulation of the cdk2 inhibitor p27(Kip1) and downregulation of cyclin D1 expression, which leads to a complete arrest of the cells in phase G(1). In contrast, cGMP inhibits cyclin D1 expression, inhibits cdk4 activation, and delays platelet-derived growth factor-mediated cdk2 activation, resulting in a delay in G(1)/S transition. A transient increase in p27(Kip1) in cdk2 immunoprecipitates, without changes in total cellular p27(Kip1) levels, correlates with the delay in cdk2 activation caused by cGMP. Thus, cAMP and cGMP differentially affect cell cycle through distinct regulation of cell cycle molecules in human SMCs.
    Preview · Article · Dec 1999 · Circulation Research
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    ABSTRACT: To elucidate the physiological role of protein kinase C (PKC) delta, a ubiquitously expressed isoform in vascular smooth muscle cells (VSMC), PKC delta was stably overexpressed in A7r5 cells, rat clonal VSMC. The [3H]thymidine incorporation in A7r5 overexpressed with PKC delta (DVs) was suppressed to 37.1 +/- 16.3% (mean +/- S.D.) of the level in control or A7r5 transfected with vector alone (EVs). The reduction of [3H]thymidine incorporation was strongly correlated with overexpressed PKC levels. Moreover, transient transfection of a dominant negative mutant of PKC delta restored the reduced proliferation in DVs. Flow cytometry analysis demonstrated that DVs were arrested in the G0/G1 phase of the cell cycle. Expression of cyclins D1 and E and retinoblastoma protein phosphorylation were reduced, while the protein levels of p27 were elevated in DVs as compared with EVs. There were no significant differences in the expression of c-fos, c-jun, c-myc, cyclin D2, D3, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and p21 among the clones. We conclude that PKC delta inhibits the proliferation of VSMC by arresting cells in G1 via mainly inhibiting the expression of cyclin D1 and cyclin E.
    No preview · Article · Jun 1997 · Journal of Biological Chemistry

Publication Stats

370 Citations
39.12 Total Impact Points


  • 2011-2014
    • Shirasagi Hospital
      Ōsaka, Ōsaka, Japan
  • 1997-2013
    • Osaka City University
      • • Department of Metabolism, Endocrinology, and Molecular Medicine
      • • Second Department of Internal Medicine
      Ōsaka, Ōsaka, Japan