Ōsaka, Japan
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Yamamoto T.,Shirasagi Hospital | Shoji S.,Shirasagi Hospital | Yamakawa T.,Shirasagi Hospital | Wada A.,Data and Society | And 3 more authors.
American Journal of Kidney Diseases | Year: 2015

Background To date, very few studies have been carried out on the associations of pre- and postdialysis acid-base parameters with mortality in hemodialysis patients. Study Design An observational study including cross-sectional and 1-year analyses. Setting & Participants Data from the renal registry of the Japanese Society of Dialysis Therapy (2008-2009), including 15,132 dialysis patients 16 years or older. Predictor Predialysis pH < 7.30, 7.30 to 7.34 (reference), 7.35 to 7.39, or 7.40 (1,550, 4,802, 6,023, and 2,757 patients, respectively); predialysis bicarbonate level < 18.0, 18.0 to 21.9 (reference), 22.0 to 25.9, or 26.0 mEq/L (2,724, 7,851, 4,023, and 534 patients, respectively); postdialysis pH < 7.40, 7.40 to 7.44, 7.45 to 7.49 (reference), or 7.50 (2,114, 5,331, 4,975, and 2,712 patients, respectively); and postdialysis bicarbonate level < 24.0, 24.0 to 25.9, 26.0 to 27.9 (reference), or 28.0 mEq/L (5,087, 4,330, 3,451, and 2,264 patients, respectively). Outcomes All-cause and cardiovascular (CV) mortality during the 1-year follow-up. Measurements HRs were estimated using unadjusted models and models adjusted for age, sex, dialysis vintage, history of CV disease, diabetes, weight gain ratio, body mass index, calcium-phosphorus product, serum albumin level, serum total cholesterol level, blood hemoglobin level, single-pool Kt/V, and normalized protein catabolic rate. Results Of 15,132 patients, during follow-up, 1,042 died of all causes, including 408 CV deaths. In the adjusted analysis for all-cause mortality, HRs compared to the reference group were significantly higher in patients with predialysis pH 7.40 (HR, 1.36; 95% CI, 1.13-1.65) and postdialysis pH < 7.40 (HR, 1.22; 95% CI, 1.00-1.49). Predialysis pH 7.40 was also associated with higher risk of CV mortality (HR, 1.34; 95% CI, 1.01-1.79). No association of pre- or postdialysis bicarbonate level with all-cause and CV mortality was observed. Limitations Single measurements of acid-base parameters, short duration of follow-up, small number of CV deaths. Conclusions Predialysis pH 7.40 was associated with significantly elevated risk of all-cause and CV mortality. However, pre- and postdialysis bicarbonate levels were not associated with all-cause and CV mortality. Predialysis pH may be the most appropriate reference for accurate correction of metabolic acidosis in dialysis patients. © 2015 National Kidney Foundation, Inc.

Okuno S.,Shirasagi Hospital | Ishimura E.,Osaka City University | Tsuboniwa N.,Shirasagi Hospital | Norimine K.,Shirasagi Hospital | And 6 more authors.
Osteoporosis International | Year: 2013

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. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.

Shoji T.,Osaka City University | Maekawa K.,Shirasagi Hospital | Emoto M.,Osaka City University | Okuno S.,Shirasagi Hospital | And 4 more authors.
Atherosclerosis | Year: 2010

Objective: Both arterial thickness and stiffness are predictors of cardiovascular disease (CVD). Although these arterial changes develop in parallel, no study has ever tested a hypothesis that arterial stiffness can predict mortality from CVD independent of arterial thickness. This study tested this possibility. Methods: This was an observational cohort study in 423 hemodialysis patients (CKD stage 5D). We simultaneously measured intima-media thickness (CA-IMT) and stiffness parameter β (CA-β) by carotid ultrasonography at baseline, and the cohort was followed-up for a mean period of 70 months. Results: During the follow-up, 216 all-cause deaths occurred including 124 deaths from CVD. Univariate analyses indicated both CA-IMT and CA-β were significant predictors for CVD death. Kaplan-Meier analysis, in which the total subjects were divided into four groups by the medians of CA-IMT and CA-β, showed that the hazards ratio (95% confidence interval) was 5.87 (3.43-10.05) for the group with higher CA-IMT/higher CA-β as compared to the group with lower CA-IMT/lower CA-β. The hazards ratios for the group with lower CA-IMT/higher CA-β (2.22, 1.16-4.25) and the group with higher CA-IMT/lower CA-β (2.85, 1.52-5.33) were comparable. Multivariate Cox analysis revealed that both CA-IMT and CA-β were independently predictive of CVD mortality even after adjustment for other relevant covariates. Conclusion: Increased arterial stiffness predicted cardiovascular mortality independent of arterial thickness in this cohort, implicating the distinct roles of stiffness and thickness of arterial wall in the pathogenesis of CVD. © 2009 Elsevier Ireland Ltd.

Inaba M.,Osaka City University | Okuno S.,Shirasagi Hospital | Imanishi Y.,Osaka City University | Ishimura E.,Osaka City University | And 2 more authors.
Osteoporosis International | Year: 2013

We reported previously that serum parathyroid hormone [PTH(1-84)]/intact PTH[PTH(1-84) + PTH(7-84)] ratio provides the better marker for parathyroid function and bone turnover state than serum PTH level itself. The present study demonstrated that higher PTH(1-84)/intact PTH ratio, but not serum PTH(1-84) and intact PTH, predicted higher all-cause mortality in 177 male hemodialysis patients. Introduction: We reported that PTH(1-84)/intact PTH ratio provides a clinically relevant marker for parathyroid function and the resultant bone turnover state. The purpose of our study was to investigate the association of PTH(1-84)/intact PTH ratio with all-cause mortality (ACM) in male hemodialysis patients. Methods: The study was performed for 70 months. Serum PTH in 177 male hemodialysis patients was measured with PTH(1-84)-specific whole PTH assay and intact PTH assay which cross-reacts with N-truncated PTH including PTH(7-84). Results: The patients (n = 177) were divided into higher and lower halves based on serum levels of PTH(1-84)/intact PTH ratio (cutoff value, 0.484), intact PTH (143.8 pg/mL), and PTH(1-84) (64.1 pg/mL). In Kaplan-Meier analysis, the higher group in whole PTH/intact PTH ratio had significantly higher ACM than the lower group (P = 0.020 by log-rank test), in contrast with the insignificant difference between the higher and lower groups in intact PTH and PTH(1-84). Multivariate Cox regression hazard analysis identified higher log [PTH(1-84)/intact PTH ratio], but not log intact PTH or log PTH(1-84) as a significant independent predictor [hazard ratio 14.428 (95 % CI 2.486-83.728)] for ACM after adjustment for various factors including age, hemodialysis duration, presence/absence of diabetes mellitus, BMI, log C-reactive protein, serum albumin, calcium, and phosphate. The association existed between log [PTH(1-84)/intact PTH ratio] and ACM in those without vitamin D administration (n = 95). Conclusion: Higher PTH(1-84)/intact PTH ratio, which provides a relevant marker for parathyroid function, may be a significant predictor of ACM in male hemodialysis patients. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.

Shoji S.,Shirasagi Hospital | Inaba M.,Osaka City University | Tomosugi N.,Kanazawa Medical University | Okuno S.,Shirasagi Hospital | And 3 more authors.
European Journal of Haematology | Year: 2013

Background: The potency of darbepoetin-α (DPO-α) to improve anemia in hemodialysis (HD) patients is greater than that of recombinant human erythropoietin (rHuEPO). Design and methods: To assess the potency of DPO-α to mobilize iron from body stores in comparison with rHuEPO in HD patients without apparent inflammation or infection, serum iron, transferrin saturation (TSAT), ferritin, and hepcidin-25 were measured serially. This study included (i) a long-term crossover study for 3 yr to compare the effects of the two erythropoiesis-stimulating agents (ESA) on serum iron, TSAT, and ferritin, and (ii) a short-term crossover study for 8 wk to examine their effects on serum hepcidin-25 in HD patients. Results: The long-term crossover study demonstrated that the change of ESA from rHuEPO to DPO-α significantly decreased serum ferritin while serum iron and TSAT remained unchanged, while DPO-α as well as rHuEPO maintained hemoglobin level in the target range between 10.0 and 11.0 g/dL. Furthermore, in the short-term crossover study, area under the percent suppression of serum hepcidin-25 time curve for the first 7 d during the DPO-α treatment period was significantly greater than that during the rHuEPO period (348.0 ± 92.4 vs. 178.4 ± 131.5%.day P = 0.030). The greater suppression of hepcidin-25 by DPO-α may facilitate iron mobilization, resulting in diminution of body iron stores without any significant effect on serum iron utilizable for erythropoiesis. Conclusion: This study demonstrated that DPO-α has a greater advantage than rHuEPO in that it facilitates iron mobilization from body stores into bone marrow to induce effective erythropoiesis and thus could protect against possible harmful effects caused by excessive iron stores in the body. © 2013 John Wiley & Sons A/S.

Kobayashi I.,Osaka City University | Ishimura E.,Osaka City University | Kato Y.,Shirasagi Hospital | Okuno S.,Shirasagi Hospital | And 5 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Malnutrition is a common complication in haemodialysis patients. Recently, the Geriatric Nutritional Risk Index (GNRI) has been reported as a simple and accurate tool to assess nutritional status of haemodialysis patients. Our objective was to examine the association between GNRI and mortality in chronic haemodialysis patients.Methods. We examined the GNRI of 490 maintenance haemodialysis patients (60 ± 12 years, 293 males and 197 females) and followed up these patients for 60 months. Predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional analyses. Results. The GNRI was 98.0 ± 6.0, and was significantly and negatively correlated with age and haemodialysis duration. During the 60-month follow-up period, 129 patients died. According to the highest positive likelihood and risk ratios, the cutoff value of GNRI for mortality was set at 90. Kaplan-Meier analysis revealed that patients with a GNRI <90 (n = 50) had a significantly lower survival rate, compared to those with GNRI ≥90 (n = 440) (log-rank test, P < 0.0001). Multivariate Cox proportional hazards analyses demonstrated that GNRI was a significant predictor for mortality [hazard ratio (HR) 0.962, 95% confidence interval (CI) 0.931-0.995, P < 0.05], after adjustment for age, gender, C-reactive protein, presence of diabetes and haemodialysis duration. Conclusions. These results demonstrated that GNRI is a significant predictor for mortality in haemodialysis patients. The simple method of GNRI is considered to be a clinically useful marker for the assessment of nutritional status in haemodialysis patients. © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Okuno S.,Shirasagi Hospital | Ishimura E.,Osaka City University | Norimine K.,Shirasagi Hospital | Tsuboniwa N.,Shirasagi Hospital | And 8 more authors.
Osteoporosis International | Year: 2012

Summary 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. Introduction 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. Methods 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 Xray 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. Results 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. Conclusion 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. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.

PubMed | Shirasagi Hospital, Osaka University of Pharmaceutical Sciences, Osaka Medical College and a Cardiovascular Pharmacotherapy and Toxicology and.
Type: | Journal: Xenobiotica; the fate of foreign compounds in biological systems | Year: 2017

1.Drug-induced liver injury is difficult to predict at the pre-clinical stage. This study aimed to clarify the roles of caspase-8 and -9 in CYP2E1 metabolite-induced liver injury in both rats and cell cultures in vitro treated with carbon tetrachloride (CCl

Yamamoto T.,Shirasagi Hospital | Nagasue K.,Shirasagi Hospital | Okuno S.,Shirasagi Hospital | Yamakawa T.,Shirasagi Hospital
Peritoneal Dialysis International | Year: 2010

Background: Severe peritoneal injury and encapsulating peritoneal sclerosis (EPS) as complications of long-term peritoneal dialysis (PD) are issues of concern. The usefulness of peritoneal lavage after withdrawal of PD and the risk factors for EPS have not been addressed until now. Little is known about mesothelial cell area (MCA) in the effluent as a marker of peritoneal injury. In the present study, we investigated the clinical significance of peritoneal lavage after PD withdrawal and tried to clarify the risk factors related to MCA, with the aim of preventing EPS. We also developed an algorithm for the clinical management of long-term PD patients. Methods: We assigned 247 PD patients to one of two cohorts after PD withdrawal: a non-lavage group (73 patients) and a lavage group (174 patients). To clarify the risk factors, we studied these potential predictors: PD duration, dialysate-to-plasma ratio of creatinine (D/P Cr) at the time of PD withdrawal, frequency of peritoneal lavage, type of PD or lavage solution, MCA at the time of PD withdrawal ("PD area"), and MCA at the time of peritoneal lavage withdrawal or censoring ("LA area"). Recurrent intestinal obstruction was defined as the main manifestation of EPS. Diagnostic performance and cut-off values were then calculated for the selected risk factors. Results: The overall incidence of EPS was significantly lower in the lavage group, at 6.9% (5.2% during lavage and 2.5% after lavage), than in the non-lavage group, at 15.1%. The risk factors and cut-off values were PD area (350 μm 2) and PD duration (78 months) for the non-lavage group; and PD area (350 μm 2) and LA area (320 μm 2) for the lavage group. Patients with a PD duration of 78 months or more and a PD area of 350 μm 2 or more were defined as high-risk patients in the non-lavage group (risk ratio: 11.14), and patients with a PD area of 350 μm 2 or more and an LA area of 320 μm 2 or more were defined as high-risk patients in the lavage group (risk ratio: 10.43). Conclusions: Peritoneal lavage is effective in reducing the incidence of EPS after PD withdrawal. The PD duration and MCA are significant risk factors, and these markers are useful for classifying patients into low- and high-risk groups for the development of EPS. © 2010 International Society for Peritoneal Dialysis.

PubMed | Kumamoto University, Shirasagi Hospital, Osaka Medical College and Osaka University of Pharmaceutical Sciences
Type: Journal Article | Journal: Basic & clinical pharmacology & toxicology | Year: 2016

Prothrombin time (PT) can reportedly be falsely prolonged by the antimicrobial drug daptomycin (DAP), and concomitant use of phosphatidylglycerol (PG). Although high doses of DAP (>6 mg/kg/day) are recommended for severe infection and result in a high blood concentration, the extent to which high blood concentrations of DAP interfere with PT, in the presence or absence of PG, has yet to be determined when using the HemosIL RecombiPlasTin 2G (Werfen Japan, Tokyo, Japan). We examined the effects of high doses of DAP on PT using this reagent. DAP (0-500 mg/L) was added to normal plasma and plasma with an already prolonged PT in the presence or absence of liposomal amphotericin B (L-AMB, 5-50 mg/L) or COATSOME EL-01 empty cationic liposomes (CS, 25-250 mg/L). Furthermore, we undertook a Monte Carlo simulation to calculate the probability of achieving DAP concentrations >100, >200 and >500 mg/L 0-48 hr after administering 6-12 mg/kg of DAP. Apparent PT increased with increasing DAP concentration, but neither L-AMB nor CS appeared to further elevate PT when co-administered with DAP. The probability of achieving DAP concentrations >100 and >200 mg/L increased with DAP dose. Higher doses of DAP than the approved dose caused false prolongation of PT. PT should be monitored carefully in patients taking high doses of DAP; ideally, PT should be measured at the trough blood concentration of DAP. Concomitant use of L-AMB and CS did not generally further elevate PT when co-administered with DAP.

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