Katsuhito Mori - Academia.edu (original) (raw)
Papers by Katsuhito Mori
Acta Endocrinologica (Bucharest), 2017
Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D... more Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). Objective. In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. Design, Subjects and Methods. This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. Results. Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m 2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. Conclusions. We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.
Nutrients, 2022
Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in low... more Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01–0.04) kgf/kg] as compared to the non-carnitine group [−0.02 (−0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive asso...
Nihon Toseki Igakkai Zasshi
Nutrients
Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal s... more Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. Methods: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. Results: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 μIU/mL, which were withi...
Kidney and Blood Pressure Research, 2021
Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source ... more Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. Methods: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57–75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. Results: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated ...
Kidney and Blood Pressure Research, 2020
Background: Cr is secreted by the proximal tubules and thus Cr clearance (Ccr) can overestimate i... more Background: Cr is secreted by the proximal tubules and thus Cr clearance (Ccr) can overestimate inulin clearance (Cin). However, in some cases, Ccr can even underestimate Cin. This suggests that Cr could be reabsorbed in the tubuli. We examined the clinical parameters that are associated with tubular Cr reabsorption. Methods: In 80 kidney donor candidates (53.9 ± 13.2 years, 29 males), Cin and para-aminohippuric acid clearance were measured simultaneously. Intrarenal hemodynamic parameters were calculated by Gomez’s formulae. To quantify the secretory component of Ccr (SFcr), it was calculated as follows: SFcr = (Ccr − Cin)/Ccr. Results: Twenty-five subjects (31.3%) showed SFcr values <0. SFcr that correlated significantly and negatively with efferent arteriolar resistance (Re) and glomerular hydrostatic pressure (Pglo) (Re: r = −0.30, p = 0.008; Pglo: r = −0.28, p = 0.025). In multiple regression analyses, Re and Pglo were significantly and negatively associated with SFcr after ...
Background: Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabe... more Background: Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, the in vitro test (T50-test) was developed for the determination of serum calcification propensity. This cross-sectional study investigated the association between serum zinc and T50 in type 2 diabetes mellitus patients and the effect of zinc on T50in vitro.Methods: The subjects were 132 type 2 diabetes mellitus patients with various kidney function. We measured T50 levels by the established nephelometric method.Results: The median (interquartile range) levels of T50 and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level was significantly and positively correlated with T50 (rs = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnes...
Diabetes and Vascular Disease Research, 2018
Decreased plasma n-3 polyunsaturated fatty acid levels or the n-3/n-6 polyunsaturated fatty acid ... more Decreased plasma n-3 polyunsaturated fatty acid levels or the n-3/n-6 polyunsaturated fatty acid ratios are associated with a risk of cardiovascular events. In this cross-sectional study, we measured plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid and investigated the association between the plasma polyunsaturated fatty acid profile and vascular endothelial function in 396 patients with type 2 diabetes. Endothelium-dependent, flow-mediated dilatation of the brachial artery was measured using ultrasonography. Multiple regression analyses, including age, sex, body mass index, and other cardiovascular risk factors, revealed that plasma eicosapentaenoic acid levels ( β = 0.140, p = 0.008) and the eicosapentaenoic acid/arachidonic acid ratio ( β = 0.127, p = 0.019), but not plasma docosahexaenoic acid levels ( β = 0.067, p = 0.220) or the docosahexaenoic acid/arachidonic acid ratio ( β = 0.034, p = 0.559), were independently and positively associated wi...
The Journal of Japan Atherosclerosis Society, 1997
Journal of diabetes research, 2016
Aim. C1q/tumor necrosis factor-related protein-9 (CTRP9), a paralog of adiponectin, is expressed ... more Aim. C1q/tumor necrosis factor-related protein-9 (CTRP9), a paralog of adiponectin, is expressed in adipose tissue. CTRP9 exerts protective effects against obesity and atherosclerosis in rodents. We investigated the association between plasma CTRP9 levels and atherosclerosis in patients with type 2 diabetes. Methods. We included 419 patients with type 2 diabetes, 161 of whom had chronic kidney disease (CKD). Fasting plasma CTRP9 and total adiponectin levels were measured with enzyme-linked immunosorbent assay. The intima-media thickness (IMT) of the common carotid artery was measured with ultrasonography. Results. Plasma CTRP9 levels were higher in the CKD group than in the non-CKD group. Plasma CTRP9 levels were positively correlated with carotid IMT in the non-CKD group. Multivariate analyses revealed that plasma CTRP9 levels were positively associated with carotid IMT in the non-CKD group, independent of age, sex, body mass index, adiponectin, and other cardiovascular risk factor...
Nephrology Dialysis Transplantation, 2015
Journal of Atherosclerosis and Thrombosis, 2017
The cardiothoracic ratio (CTR) on a chest X-ray is an indicator of cardiac enlargement, although ... more The cardiothoracic ratio (CTR) on a chest X-ray is an indicator of cardiac enlargement, although its predictive power for cardiovascular disease (CVD) events in chronic kidney disease is unknown. We examined it in a cohort of hemodialysis patients, as compared with an N-terminal fragment of probrain natriuretic peptide (NT-proBNP). Method: This was an observational study with cross-sectional and longitudinal analyses including 517 maintenance hemodialysis patients and 122 healthy control subjects. The main predictors were CTR and serum NT-proBNP, and the main outcome was CVD events in 5 years. Results: At baseline, the hemodialysis patients had higher median (interquartile range) levels of CTR [0.487 (0.457-0.520)] than the control group [0.458 (0.432-0.497)]. In the hemodialysis group, CTR was positively correlated with NT-proBNP (Spearman's r 0.44, P 0.001). During follow-up, 190 CVD events occurred. CTR was significantly associated with the risk of CVD [HR 2.12 (95% CI, 1.38-3.25) for the fourth quartile as compared with the second quartile of CTR] in a multivariate Cox model. In the same model, NT-proBNP (fourth versus first quartile) showed a HR of 3.27 (2.02-5.31). When CTR and NT-proBNP were simultaneously included as predictors, only NT-proBNP remained a significant predictor of CVD events, all-cause mortality and composite of CVD plus all-cause mortality. Conclusions: We showed that CTR was a significant and independent predictor of CVD in hemodialysis patients. CTR can be used for CVD risk stratification in hemodialysis patients when NT-proBNP is not available.
Journal of Atherosclerosis and Thrombosis, 2007
The present study aimed to clarify the clinical impact of modified NCEP-ATP criteria for metaboli... more The present study aimed to clarify the clinical impact of modified NCEP-ATP criteria for metabolic syndrome (MS) and Framingham Risk Score (FRS) on carotid atherosclerosis in 615 Japanese adults (319 men and 296 women) including 307 with type 2 diabetes. Methods: Waist circumference was the only component from the original NCEP-ATP criteria based on Japanese criteria. The intima-medial thickness (IMT) and stiffness parameter of the carotid artery were measured by ultrasound. Results: Both IMT and stiffness parameter were significantly increased with the number of coexisting components of MS, and higher in subjects with MS than in those without MS (all Ps 0.0001). In a logistic regression analysis with each component of MS as independent factors, hyperglycemia and hypertension had the highest odds ratio for progressors of IMT and stiffness parameter , respectively. Univariate odds ratios of MS for both IMT and stiffness parameter were comparable with that of an increase of 10% in 10-year coronary heart disease (CHD) risk by FRS (CHD risk/ 10%) but inferior to CHD risk by FRS 20%. Conclusion: The modified NCEP-ATP criteria for MS revealed an additive predictive impact on carotid atherosclerosis but no superiority to FRS.
Osaka city medical journal, 2012
Although poor glycemic control is known as an independent predictor of mortality in diabetic hemo... more Although poor glycemic control is known as an independent predictor of mortality in diabetic hemodialysis patients, it is often difficult for some patients to perform standard self injection insulin therapy. Some practical methods are needed for such patients. We evaluated the usefulness of a new regimen of insulin therapy, namely thrice-weekly insulin injection with nurse's support (TWINS) using insulin NPH or glargine at the end of each hemodialysis sessions in 5 outpatients on hemodialysis with type 2 diabetes mellitus showing HbAlc levels > or = 8.0% (JDS). HbA1c levels were successfully decreased in all patients from 9.3 +/- 1.1% to 6.9 +/- 0.7% (mean +/- SD) in six months without hypoglycemia symptoms. These preliminary results suggest that this regimen can be one of the practical choices in poor-controlled diabetes patients on regular hemodialysis who have difficulty in self injection of insulin.
[Rinshō ketsueki] The Japanese journal of clinical hematology, 2011
A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bon... more A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.
Nephrology Dialysis Transplantation, 2011
Background. To date, little proteomic information has been available from the glomeruli of diabet... more Background. To date, little proteomic information has been available from the glomeruli of diabetic patients, possibly due to the clinical limitations of renal biopsy in diabetic patients and insufficient quantities of such specimens for proteome analysis. The purpose of the present study was to identify altered protein expression profiles in diabetic glomeruli using formalin-fixed paraffin-embedded (FFPE) kidney tissues from diabetic patients. Methods. Glomeruli were laser microdissected from FFPE autopsy kidney tissues from 10 patients with diabetic nephropathy and 10 non-diabetic control patients and underwent proteome analysis using QSTAR Elite liquid chromatography with tandem mass spectrometry and iTRAQ technology. Immunohistochemical analysis was performed on 93 autopsy samples from diabetic patients with and without nephropathy (n ¼ 45 and n ¼ 48, respectively). Results. Thirty-one renal and urological disease-related proteins displayed a differential abundance in glomerular samples from patients with diabetic nephropathy compared with non-diabetic control patients. Among them, we found that nephronectin, which functions in the assembly of extracellular matrix, showed clearly positive immunoreactivity in diabetic glomeruli. The numerical fraction of nephronectinpositive glomerular cross sections was increased significantly in diabetic patients with nephropathy compared to those without nephropathy (32.1 6 31.5 versus 4.14 6 5.65%, P < 0.0001). Furthermore, there was a significant positive correlation between this numerical fraction of nephronectinpositive glomerular cross sections and the glomerular sclerosis index (q ¼ 0.881, P < 0.0001, n ¼ 93). Conclusion. The present study demonstrated, for the first time, that nephronectin may be associated with the development of diabetic glomerulosclerosis and that proteome analysis with FFPE kidney tissues from diabetic patients with nephropathy is useful in understanding diabetic nephropathy.
The Journal of Clinical Endocrinology & Metabolism, 2006
Context: Impaired nonoxidative glucose disposal and decrease in mitochondrial glucose oxidation b... more Context: Impaired nonoxidative glucose disposal and decrease in mitochondrial glucose oxidation both contribute to insulin resistance in diabetic subjects. Objective: In the present study, we investigated whether plasma adiponectin is associated with glucose oxidation and nonoxidative glucose disposal in subjects with and without type 2 diabetes. Design: Euglycemic-hyperinsulinemic clamp was performed in 42 type 2 diabetic (T2DM) and 13 nondiabetic (non-DM) subjects. The whole-body glucose disposal rate (GDR) was evaluated as the mean of the glucose infusion rate during steady state of the clamp. Glucose and fat oxidation rates were assessed by indirect calorimetry, and nonoxidative glucose disposal rate was calculated by subtracting glucose oxidation rate from GDR. Results: Plasma adiponectin level was significantly lower in T2DM than non-DM (2.87 Ϯ 1.40 vs. 3.96 Ϯ 2.39 g/ml, P ϭ 0.045). GDR (3.39 Ϯ 1.53 vs. 4.83 Ϯ 1.70 mg/kg⅐min, P ϭ 0.006) and nonoxidative glucose disposal rate (1.89 Ϯ 1.39 vs. 3.11 Ϯ 1.76 mg/kg⅐min, P ϭ 0.012) were significantly lower in T2DM, compared with non-DM, although no difference was found in glucose oxidation rate between the two groups. In all subjects, plasma adiponectin level was positively correlated with GDR (r ϭ 0.351, P ϭ 0.009) and nonoxidative glucose disposal rate (r ϭ 0.324, P ϭ 0.016) but not glucose oxidation rate. There was no significant correlation between plasma adiponectin level and fat oxidation, either before or during the clamp. Conclusions: In conclusion, plasma adiponectin level is associated with nonoxidative glucose disposal, which is reduced in type 2 diabetic subjects. Our results suggest that adiponectin controls insulin sensitivity by modulating the glycogen synthetic process in human skeletal muscle.
Circulation Research, 2000
Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic a... more Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (Ͼ1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Osf2/Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org. (Circ Res. 2000;87:e10-e17.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objectives— Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved i... more Objectives— Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects. Methods and Results— Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176±0.092 ng/mL) than nondiabetic controls (0.253±0.111). Of note...
PLoS ONE, 2014
Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance ... more Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) c, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARcactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.
Acta Endocrinologica (Bucharest), 2017
Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D... more Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). Objective. In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. Design, Subjects and Methods. This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. Results. Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m 2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. Conclusions. We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.
Nutrients, 2022
Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in low... more Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01–0.04) kgf/kg] as compared to the non-carnitine group [−0.02 (−0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive asso...
Nihon Toseki Igakkai Zasshi
Nutrients
Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal s... more Purpose: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. Methods: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. Results: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 μIU/mL, which were withi...
Kidney and Blood Pressure Research, 2021
Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source ... more Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. Methods: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57–75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. Results: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated ...
Kidney and Blood Pressure Research, 2020
Background: Cr is secreted by the proximal tubules and thus Cr clearance (Ccr) can overestimate i... more Background: Cr is secreted by the proximal tubules and thus Cr clearance (Ccr) can overestimate inulin clearance (Cin). However, in some cases, Ccr can even underestimate Cin. This suggests that Cr could be reabsorbed in the tubuli. We examined the clinical parameters that are associated with tubular Cr reabsorption. Methods: In 80 kidney donor candidates (53.9 ± 13.2 years, 29 males), Cin and para-aminohippuric acid clearance were measured simultaneously. Intrarenal hemodynamic parameters were calculated by Gomez’s formulae. To quantify the secretory component of Ccr (SFcr), it was calculated as follows: SFcr = (Ccr − Cin)/Ccr. Results: Twenty-five subjects (31.3%) showed SFcr values <0. SFcr that correlated significantly and negatively with efferent arteriolar resistance (Re) and glomerular hydrostatic pressure (Pglo) (Re: r = −0.30, p = 0.008; Pglo: r = −0.28, p = 0.025). In multiple regression analyses, Re and Pglo were significantly and negatively associated with SFcr after ...
Background: Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabe... more Background: Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, the in vitro test (T50-test) was developed for the determination of serum calcification propensity. This cross-sectional study investigated the association between serum zinc and T50 in type 2 diabetes mellitus patients and the effect of zinc on T50in vitro.Methods: The subjects were 132 type 2 diabetes mellitus patients with various kidney function. We measured T50 levels by the established nephelometric method.Results: The median (interquartile range) levels of T50 and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level was significantly and positively correlated with T50 (rs = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnes...
Diabetes and Vascular Disease Research, 2018
Decreased plasma n-3 polyunsaturated fatty acid levels or the n-3/n-6 polyunsaturated fatty acid ... more Decreased plasma n-3 polyunsaturated fatty acid levels or the n-3/n-6 polyunsaturated fatty acid ratios are associated with a risk of cardiovascular events. In this cross-sectional study, we measured plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid and investigated the association between the plasma polyunsaturated fatty acid profile and vascular endothelial function in 396 patients with type 2 diabetes. Endothelium-dependent, flow-mediated dilatation of the brachial artery was measured using ultrasonography. Multiple regression analyses, including age, sex, body mass index, and other cardiovascular risk factors, revealed that plasma eicosapentaenoic acid levels ( β = 0.140, p = 0.008) and the eicosapentaenoic acid/arachidonic acid ratio ( β = 0.127, p = 0.019), but not plasma docosahexaenoic acid levels ( β = 0.067, p = 0.220) or the docosahexaenoic acid/arachidonic acid ratio ( β = 0.034, p = 0.559), were independently and positively associated wi...
The Journal of Japan Atherosclerosis Society, 1997
Journal of diabetes research, 2016
Aim. C1q/tumor necrosis factor-related protein-9 (CTRP9), a paralog of adiponectin, is expressed ... more Aim. C1q/tumor necrosis factor-related protein-9 (CTRP9), a paralog of adiponectin, is expressed in adipose tissue. CTRP9 exerts protective effects against obesity and atherosclerosis in rodents. We investigated the association between plasma CTRP9 levels and atherosclerosis in patients with type 2 diabetes. Methods. We included 419 patients with type 2 diabetes, 161 of whom had chronic kidney disease (CKD). Fasting plasma CTRP9 and total adiponectin levels were measured with enzyme-linked immunosorbent assay. The intima-media thickness (IMT) of the common carotid artery was measured with ultrasonography. Results. Plasma CTRP9 levels were higher in the CKD group than in the non-CKD group. Plasma CTRP9 levels were positively correlated with carotid IMT in the non-CKD group. Multivariate analyses revealed that plasma CTRP9 levels were positively associated with carotid IMT in the non-CKD group, independent of age, sex, body mass index, adiponectin, and other cardiovascular risk factor...
Nephrology Dialysis Transplantation, 2015
Journal of Atherosclerosis and Thrombosis, 2017
The cardiothoracic ratio (CTR) on a chest X-ray is an indicator of cardiac enlargement, although ... more The cardiothoracic ratio (CTR) on a chest X-ray is an indicator of cardiac enlargement, although its predictive power for cardiovascular disease (CVD) events in chronic kidney disease is unknown. We examined it in a cohort of hemodialysis patients, as compared with an N-terminal fragment of probrain natriuretic peptide (NT-proBNP). Method: This was an observational study with cross-sectional and longitudinal analyses including 517 maintenance hemodialysis patients and 122 healthy control subjects. The main predictors were CTR and serum NT-proBNP, and the main outcome was CVD events in 5 years. Results: At baseline, the hemodialysis patients had higher median (interquartile range) levels of CTR [0.487 (0.457-0.520)] than the control group [0.458 (0.432-0.497)]. In the hemodialysis group, CTR was positively correlated with NT-proBNP (Spearman's r 0.44, P 0.001). During follow-up, 190 CVD events occurred. CTR was significantly associated with the risk of CVD [HR 2.12 (95% CI, 1.38-3.25) for the fourth quartile as compared with the second quartile of CTR] in a multivariate Cox model. In the same model, NT-proBNP (fourth versus first quartile) showed a HR of 3.27 (2.02-5.31). When CTR and NT-proBNP were simultaneously included as predictors, only NT-proBNP remained a significant predictor of CVD events, all-cause mortality and composite of CVD plus all-cause mortality. Conclusions: We showed that CTR was a significant and independent predictor of CVD in hemodialysis patients. CTR can be used for CVD risk stratification in hemodialysis patients when NT-proBNP is not available.
Journal of Atherosclerosis and Thrombosis, 2007
The present study aimed to clarify the clinical impact of modified NCEP-ATP criteria for metaboli... more The present study aimed to clarify the clinical impact of modified NCEP-ATP criteria for metabolic syndrome (MS) and Framingham Risk Score (FRS) on carotid atherosclerosis in 615 Japanese adults (319 men and 296 women) including 307 with type 2 diabetes. Methods: Waist circumference was the only component from the original NCEP-ATP criteria based on Japanese criteria. The intima-medial thickness (IMT) and stiffness parameter of the carotid artery were measured by ultrasound. Results: Both IMT and stiffness parameter were significantly increased with the number of coexisting components of MS, and higher in subjects with MS than in those without MS (all Ps 0.0001). In a logistic regression analysis with each component of MS as independent factors, hyperglycemia and hypertension had the highest odds ratio for progressors of IMT and stiffness parameter , respectively. Univariate odds ratios of MS for both IMT and stiffness parameter were comparable with that of an increase of 10% in 10-year coronary heart disease (CHD) risk by FRS (CHD risk/ 10%) but inferior to CHD risk by FRS 20%. Conclusion: The modified NCEP-ATP criteria for MS revealed an additive predictive impact on carotid atherosclerosis but no superiority to FRS.
Osaka city medical journal, 2012
Although poor glycemic control is known as an independent predictor of mortality in diabetic hemo... more Although poor glycemic control is known as an independent predictor of mortality in diabetic hemodialysis patients, it is often difficult for some patients to perform standard self injection insulin therapy. Some practical methods are needed for such patients. We evaluated the usefulness of a new regimen of insulin therapy, namely thrice-weekly insulin injection with nurse's support (TWINS) using insulin NPH or glargine at the end of each hemodialysis sessions in 5 outpatients on hemodialysis with type 2 diabetes mellitus showing HbAlc levels > or = 8.0% (JDS). HbA1c levels were successfully decreased in all patients from 9.3 +/- 1.1% to 6.9 +/- 0.7% (mean +/- SD) in six months without hypoglycemia symptoms. These preliminary results suggest that this regimen can be one of the practical choices in poor-controlled diabetes patients on regular hemodialysis who have difficulty in self injection of insulin.
[Rinshō ketsueki] The Japanese journal of clinical hematology, 2011
A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bon... more A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.
Nephrology Dialysis Transplantation, 2011
Background. To date, little proteomic information has been available from the glomeruli of diabet... more Background. To date, little proteomic information has been available from the glomeruli of diabetic patients, possibly due to the clinical limitations of renal biopsy in diabetic patients and insufficient quantities of such specimens for proteome analysis. The purpose of the present study was to identify altered protein expression profiles in diabetic glomeruli using formalin-fixed paraffin-embedded (FFPE) kidney tissues from diabetic patients. Methods. Glomeruli were laser microdissected from FFPE autopsy kidney tissues from 10 patients with diabetic nephropathy and 10 non-diabetic control patients and underwent proteome analysis using QSTAR Elite liquid chromatography with tandem mass spectrometry and iTRAQ technology. Immunohistochemical analysis was performed on 93 autopsy samples from diabetic patients with and without nephropathy (n ¼ 45 and n ¼ 48, respectively). Results. Thirty-one renal and urological disease-related proteins displayed a differential abundance in glomerular samples from patients with diabetic nephropathy compared with non-diabetic control patients. Among them, we found that nephronectin, which functions in the assembly of extracellular matrix, showed clearly positive immunoreactivity in diabetic glomeruli. The numerical fraction of nephronectinpositive glomerular cross sections was increased significantly in diabetic patients with nephropathy compared to those without nephropathy (32.1 6 31.5 versus 4.14 6 5.65%, P < 0.0001). Furthermore, there was a significant positive correlation between this numerical fraction of nephronectinpositive glomerular cross sections and the glomerular sclerosis index (q ¼ 0.881, P < 0.0001, n ¼ 93). Conclusion. The present study demonstrated, for the first time, that nephronectin may be associated with the development of diabetic glomerulosclerosis and that proteome analysis with FFPE kidney tissues from diabetic patients with nephropathy is useful in understanding diabetic nephropathy.
The Journal of Clinical Endocrinology & Metabolism, 2006
Context: Impaired nonoxidative glucose disposal and decrease in mitochondrial glucose oxidation b... more Context: Impaired nonoxidative glucose disposal and decrease in mitochondrial glucose oxidation both contribute to insulin resistance in diabetic subjects. Objective: In the present study, we investigated whether plasma adiponectin is associated with glucose oxidation and nonoxidative glucose disposal in subjects with and without type 2 diabetes. Design: Euglycemic-hyperinsulinemic clamp was performed in 42 type 2 diabetic (T2DM) and 13 nondiabetic (non-DM) subjects. The whole-body glucose disposal rate (GDR) was evaluated as the mean of the glucose infusion rate during steady state of the clamp. Glucose and fat oxidation rates were assessed by indirect calorimetry, and nonoxidative glucose disposal rate was calculated by subtracting glucose oxidation rate from GDR. Results: Plasma adiponectin level was significantly lower in T2DM than non-DM (2.87 Ϯ 1.40 vs. 3.96 Ϯ 2.39 g/ml, P ϭ 0.045). GDR (3.39 Ϯ 1.53 vs. 4.83 Ϯ 1.70 mg/kg⅐min, P ϭ 0.006) and nonoxidative glucose disposal rate (1.89 Ϯ 1.39 vs. 3.11 Ϯ 1.76 mg/kg⅐min, P ϭ 0.012) were significantly lower in T2DM, compared with non-DM, although no difference was found in glucose oxidation rate between the two groups. In all subjects, plasma adiponectin level was positively correlated with GDR (r ϭ 0.351, P ϭ 0.009) and nonoxidative glucose disposal rate (r ϭ 0.324, P ϭ 0.016) but not glucose oxidation rate. There was no significant correlation between plasma adiponectin level and fat oxidation, either before or during the clamp. Conclusions: In conclusion, plasma adiponectin level is associated with nonoxidative glucose disposal, which is reduced in type 2 diabetic subjects. Our results suggest that adiponectin controls insulin sensitivity by modulating the glycogen synthetic process in human skeletal muscle.
Circulation Research, 2000
Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic a... more Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMCs cultured in media containing normal physiological levels of inorganic phosphate (1.4 mmol/L) did not mineralize. In contrast, HSMCs cultured in media containing phosphate levels comparable to those seen in hyperphosphatemic individuals (Ͼ1.4 mmol/L) showed dose-dependent increases in mineral deposition. Mechanistic studies revealed that elevated phosphate treatment of HSMCs also enhanced the expression of the osteoblastic differentiation markers osteocalcin and Osf2/Cbfa-1. The effects of elevated phosphate on HSMCs were mediated by a sodium-dependent phosphate cotransporter (NPC), as indicated by the ability of the specific NPC inhibitor phosphonoformic acid, to dose dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. With the use of polymerase chain reaction and Northern blot analyses, the NPC in HSMCs was identified as Pit-1 (Glvr-1), a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMCs to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. The full text of this article is available at http://www.circresaha.org. (Circ Res. 2000;87:e10-e17.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2005
Objectives— Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved i... more Objectives— Advanced glycation endproducts, AGEs, and its specific receptor, RAGE, are involved in diabetic vascular complications. Endogenous secretory RAGE, esRAGE, has been identified as an alternatively spliced form of RAGE, and shown to act as a decoy receptor for AGE. Here, we measured plasma esRAGE level with a recently developed enzyme-linked immunosorbent assay (ELISA) and examined its association with atherosclerosis in age- and gender-matched 203 type 2 diabetic and 134 nondiabetic subjects. Methods and Results— Plasma esRAGE was inversely associated with carotid or femoral atherosclerosis, as quantitatively measured as intimal-medial thickness (IMT) by arterial ultrasound. Stepwise regression analyses revealed that plasma esRAGE was the third strongest and independent factor associated with carotid IMT, following age and systolic blood pressure. Plasma esRAGE was significantly lower in diabetic patients (0.176±0.092 ng/mL) than nondiabetic controls (0.253±0.111). Of note...
PLoS ONE, 2014
Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance ... more Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) c, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARcactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.