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Ōsaka, Japan

Masuda M.,Osaka City University | Ishimura E.,Osaka City University | Ochi A.,Osaka City University | Tsujimoto Y.,Inoue Hospital | And 5 more authors.
Nephron - Clinical Practice | Year: 2014

Background/Aims: β2-Microglobulin (β2-MG) is a major protein component of dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, β2-MG amyloid deposits not only in osteoarticular tissues, but also in systemic tissues, including the heart. The purpose of this study was to investigate the relationship between serum β2-MG concentrations and echocardiographic parameters in long-term HD patients in a cross-sectional study. Methods: Measurement of serum β2-MG concentrations and echocardiography were performed in 251 patients who had undergone HD therapy for more than 10 years. Results: The left ventricular mass index (LVMI) of the higher serum β2-MG (≥30 mg/l) group was significantly higher than that of the lower serum β2-MG (<30 mg/l) group (151.5 ± 45.7 vs. 137.0 ± 44.5 g/m2, p = 0.020). In simple regression analyses, serum β2-MG concentrations correlated significantly and positively with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r = 0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses revealed that serum β2-MG concentrations correlated significantly and positively with IVST, PWT, LVWT and RWT. Conclusion: Serum β2-MG concentrations correlated significantly and positively with the echocardiographic parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus, deposition of β2-MG amyloid in the heart may be associated with LVH progression. © 2014 S. Karger AG, Basel. Source

Koyama H.,Osaka City University | Fukuda S.,Osaka City University | Shoji T.,Osaka City University | Inaba M.,Osaka City University | And 12 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: Despite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigue's underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD. Design, setting, participants, & measurements: 788 volunteer patients under hemodialysis therapy (506 male, 282 female) completed the survey between October and November 2005, with the follow-up period up to 26 months to monitor occurrence of fatal or nonfatal cardiovascular events. The questionnaire consisted of 64 questions, and promax rotation analysis of the principal component method conceptualized eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems, and infection. Results: 14.7% of the patients showed fatigue scores higher than twice the SD of the mean for healthy volunteers. These highly fatigued patients exhibited a significantly higher risk for cardiovascular events (hazard ratio: 2.17; P < 0.01), with the relationship independent of the well-known risk factors, including age, diabetes, cardiovascular disease history, and inflammation and malnutrition markers. Moreover, comparisons of the risk in key subgroups showed that the risk of high fatigue score for cardiovascular events was more prominent in well-nourished patients, including lower age, absence of past cardiovascular diseases, higher serum albumin, and high non-HDL cholesterol. Conclusions: Fatigue can be an important predictor for cardiovascular events in patients with ESRD, with the relationship independent of the nutritional or inflammatory status. Copyright © 2010 by the American Society of Nephrology. Source

Inaba M.,Osaka City University | Kurajoh M.,Osaka City University | Okuno S.,Shirasagi Hospital | Imanishi Y.,Osaka City University | And 5 more authors.
Clinical Nephrology | Year: 2010

Background: The serum creatinine level is significantly lower in well-nourished hemodialysis patients with diabetes mellitus (DM) than in their non-DM counterparts, despite the presence of anuria in these patients. The factors associated with this finding have not been determined. Patients and methods: We evaluated the association of serum creatinine with handgrip strength (HGS) and lean body mass index (LMI) in a cross-sectional study of 102 DM and 208 non-DM hemodialysis patients to determine if poorer muscle quality in DM patients could explain the reduced level of serum creatinine. All the DM patients were well-nourished. Grip dynamometry and dual-energy X-ray absorptiometry (DXA) were used to measure HGS and LMI, respectively. Results: The DM patients had a significantly lower serum creatinine level and HGS compared to the non-DM patients, but whole-body LMI and LMI of the upper limbs did not differ between the two groups of patients. The DM patients had significantly lower serum creatinine/whole-body LMI, serum creatinine/arm LMI, HGS/whole-body LMI, and HGS/arm LMI ratios. The serum creatinine level was significantly correlated with HGS and with whole-body and upper limb LMI in both groups of patients. However, regression analyses of LMI with serum creatinine and HGS gave significantly shallower slopes for the DM patients compared to the non-DM patients. Conclusion: This suggests that the muscle strength generated per unit of muscle mass, which is reflected well by the serum creatinine level, is significantly reduced in DM hemodialysis patients. Therefore, our results show that the significantly lower serum creatinine levels in DM hemodialysis patients compared to non-DM hemodialysis patients may be explained by poor muscle quality rather than by reduced muscle mass or malnutrition. Source

Tsujimoto M.,Kyoto Pharmaceutical University | Hatozaki D.,Kyoto Pharmaceutical University | Shima D.,Kyoto Pharmaceutical University | Yokota H.,Kyoto Pharmaceutical University | And 5 more authors.
Therapeutic Apheresis and Dialysis | Year: 2012

It is known that the lipid-lowering agent pravastatin, which is not metabolized by cytochrome P450, is eliminated as an unchanged drug in bile and urine. It is interesting to note that the non-renal clearance of pravastatin in end-stage renal failure patients is decreased compared with that of healthy volunteers. This study investigated the influence of uremic serum and toxins on the transport mechanisms of pravastatin to elucidate the cause of decreased non-renal clearance in end-stage renal failure patients. Caco-2 and Hep3B cells were used as models of intestinal epithelial cells and hepatocytes respectively. Normal and uremic serum were deproteinized by treatment with methanol. 3-Carboxy-4-methyl-5propyl-2-furanpropanoic acid (CMPF), hippuric acid, indole-3-acetic acid, 3-indoxyl sulfate, and p-cresol were chosen as uremic toxins. Uremic serum-treated Caco-2 cells exhibited significantly increased accumulation of pravastatin and significantly decreased expression of MRP2 mRNA compared with normal serum-treated Caco-2 cells. In addition, the expression of MRP2 mRNA tended to decrease in cells treated with CMPF, indole-3-acetic acid, or 3-indoxyl sulfate. Uremic serum-treated Hep3B cells showed a significantly decreased initial uptake rate of pravastatin; furthermore, the expressions of OATP1B1 and OATP2B1 mRNA were decreased compared to normal serum-treated Hep3B cells. These results suggest that the decrease in the non-renal clearance of pravastatin in end-stage renal failure patients is partly induced by the downregulation of intestinal MRP2 and hepatic OATP1B1 and/or OATP2B1 by various uremic toxins in end-stage renal failure patients. © 2012 International Society for Apheresis. Source

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. Source

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