論文 - 古橋　眞人

Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population

Takahiro Fuseya, Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Tomohiro Mita, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Marenao Tanaka, Kohei Ohno, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

CARDIOVASCULAR DIABETOLOGY ( BIOMED CENTRAL LTD )  13   126  2014年08月  [査読有り]

　概要を見る

Background: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. Methods: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. Results: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. Conclusions: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

DOI PubMed

IgA型多発性骨髄腫に伴うacute light chain tubulopathyの一例

瀬野 結, 田中 希尚, 舘越 勇輝, 青山 ちひろ, 大野 紘平, 古橋 眞人, 吉田 英昭, 坂本 孝志, 小川 弥生

日本腎臓学会誌 ( (一社)日本腎臓学会 )  56 ( 6 ) 877 - 877  2014年08月

Reduction of endoplasmic reticulum stress by 4-phenylbutyric acid prevents the development of hypoxia-induced pulmonary arterial hypertension

Masayuki Koyama, Masato Furuhashi, Shutaro Ishimura, Tomohiro Mita, Takahiro Fuseya, Yusuke Okazaki, Hideaki Yoshida, Kazufumi Tsuchihashi, Tetsuji Miura

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY ( AMER PHYSIOLOGICAL SOC )  306 ( 9 ) H1314 - H1323  2014年05月  [査読有り]

　概要を見る

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling of the pulmonary artery (PA). Recently, endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) have been disclosed in various types of diseases. Here we examined whether ER stress is involved in the pathogenesis of PAH. Four weeks of chronic normobaric hypoxia increased right ventricular (RV) systolic pressure by 63% compared with that in normoxic controls and induced RV hypertrophy and medial thickening of the PA in C57BL/6J mice. Treatment with 4-phenylbutyric acid (4-PBA), a chemical chaperone, significantly reduced RV systolic pressure by 30%, attenuated RV hypertrophy and PA muscularization, and increased total running distance in a treadmill test by 70% in hypoxic mice. The beneficial effects of 4-PBA were associated with suppressed expression of inflammatory cytokines and ER stress markers, including Grp78 and Grp94 in the activating transcription factor-6 branch, sXbp1 and Pdi in the inositol-requiring enzyme-1 branch and Atf4 in the PKR-like ER kinase branch, and reduced phosphorylation of c-Jun NH2-terminal kinase and eukaryotic translation initiation factor-2 alpha in the lung. The pattern of changes in ER stress and inflammatory markers by 4-PBA in the lung of the PAH model was reproduced in PA smooth muscle cells by chronic stimulation of platelet-derived growth factor-BB or hypoxia. Furthermore, knockdown of each UPR branch sensor activated other branches and promoted proliferation of PA smooth muscle cells. The findings indicate that activation of all branches of the UPR and accompanying inflammation play a major role in the pathogenesis of PAH, and that chemical chaperones are potentially therapeutic agents for PAH.

DOI PubMed

Small-Molecule Inhibitors of PKR Improve Glucose Homeostasis in Obese Diabetic Mice

Takahisa Nakamura, Alessandro Arduini, Brenna Baccaro, Masato Furuhashi, Goekhan S. Hotamisligil

DIABETES ( AMER DIABETES ASSOC )  63 ( 2 ) 526 - 534  2014年02月  [査読有り]

　概要を見る

Obesity and metabolic diseases appear as clusters, often featuring high risk for insulin resistance and type 2 diabetes, and constitute a major global health problem with limited treatment options. Previous studies have shown that double-stranded RNA-dependent kinase, PKR, plays an important role in the nutrient/pathogen-sensing interface, and acts as a key modulator of chronic metabolic inflammation, insulin sensitivity, and glucose homeostasis in obesity. Recently, pathological PKR activation was also demonstrated in obese humans, strengthening its prospects as a potential drug target. Here, we investigate the use of two structurally distinct small-molecule inhibitors of PKR in the treatment of insulin resistance and type 2 diabetes in cells and in a mouse model of severe obesity and insulin resistance. Inhibition of PKR reduced stress-induced Jun NH2-terminal kinase activation and insulin receptor substrate 1 serine phosphorylation in vitro and in vivo. In addition, treatment with both PKR inhibitors reduced adipose tissue inflammation, improved insulin sensitivity, and improved glucose intolerance in mice after the establishment of obesity and insulin resistance. Our findings suggest that pharmacologically targeting PKR may be an effective therapeutic strategy for the treatment of insulin resistance and type 2 diabetes.

DOI PubMed

Ectopic Expression of Fatty Acid-Binding Protein 4 in the Glomerulus Is Associated with Proteinuria and Renal Dysfunction

Marenao Tanaka, Masato Furuhashi, Yusuke Okazaki, Tomohiro Mita, Takahiro Fuseya, Kohei Ohno, Shutaro Ishimura, Hideaki Yoshida, Tetsuji Miura

NEPHRON CLINICAL PRACTICE ( KARGER )  128 ( 3-4 ) 345 - 351  2014年  [査読有り]

　概要を見る

Background/Aims: Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in proximal tubular epithelial cells in the kidney, and urinary FABP1 has been reported to reflect damage of proximal tubular epithelial cells. However, roles of other FABP isoforms in renal pathologies have not been reported. Recently, FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We examined the hypothesis that pathological conditions alter the level and localization of FABP4 expression in the kidney, which mediates renal dysfunction. Methods: A total of 112 consecutive patients who underwent renal biopsy were retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was examined by immunohistochemistry and in situ hybridization, respectively. The ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area), urinary protein level (U-Protein), and change in estimated glomerular filtration rate (eGFR) 1 year after biopsy were examined. Results: FABP4 protein and mRNA were expressed not only in PTCs, but also in endothelial cells and macrophages in the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p < 0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area was significantly larger in cases with an endocapillary proliferative lesion, and change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = -0.537, p = 0.008). Conclusion: Ectopic FABP4 expression in the glomerulus is induced by renal diseases and is closely associated with proteinuria and renal dysfunction. (C) 2015 S. Karger AG, Basel

DOI

Ectopic expression of fatty acid-binding protein 4 in the glomerulus is associated with proteinuria and renal dysfunction.

Marenao Tanaka, Masato Furuhashi, Yusuke Okazaki, Tomohiro Mita, Takahiro Fuseya, Kohei Ohno, Shutaro Ishimura, Hideaki Yoshida, Tetsuji Miura

Nephron. Clinical practice ( 3-4 )  128 ( 3-4 ) 345 - 51  2014年  [査読有り]  [国際誌]

　概要を見る

BACKGROUND/AIMS: Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in proximal tubular epithelial cells in the kidney, and urinary FABP1 has been reported to reflect damage of proximal tubular epithelial cells. However, roles of other FABP isoforms in renal pathologies have not been reported. Recently, FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We examined the hypothesis that pathological conditions alter the level and localization of FABP4 expression in the kidney, which mediates renal dysfunction. METHODS: A total of 112 consecutive patients who underwent renal biopsy were retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was examined by immunohistochemistry and in situ hybridization, respectively. The ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area), urinary protein level (U-Protein), and change in estimated glomerular filtration rate (eGFR) 1 year after biopsy were examined. RESULTS: FABP4 protein and mRNA were expressed not only in PTCs, but also in endothelial cells and macrophages in the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p < 0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area was significantly larger in cases with an endocapillary proliferative lesion, and change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = -0.537, p = 0.008). CONCLUSION: Ectopic FABP4 expression in the glomerulus is induced by renal diseases and is closely associated with proteinuria and renal dysfunction.

DOI PubMed

Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Shutaro Ishimura, Masato Furuhashi, Yuki Watanabe, Kyoko Hoshina, Takahiro Fuseya, Tomohiro Mita, Yusuke Okazaki, Masayuki Koyama, Marenao Tanaka, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE )  8 ( 11 ) e81318  2013年11月  [査読有り]

　概要を見る

Objective: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. Methods: From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1 similar to 5 in their serum samples were assayed. Results: Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMAR after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. Conclusions: Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting preclinical stage of metabolic syndrome, especially insulin resistance, in the general population.

DOI PubMed

脂肪酸結合タンパク4の脂肪細胞からの分泌機構の検討

石村 周太郎, 古橋 眞人, 美田 知宏, 伏屋 敬博, 大野 紘平, 田中 希尚, 赤坂 憲, 吉田 英昭, 平光 伸也, 石井 潤一, 三浦 哲嗣

肥満研究 ( (一社)日本肥満学会 )  19 ( Suppl. ) 176 - 176  2013年09月

メサンギウム増殖性糸球体腎炎における糸球体脂肪酸結合タンパク4発現の意義

田中 希尚, 古橋 眞人, 岡崎 雄介, 大野 紘平, 美田 知宏, 伏屋 敬博, 石村 周太郎, 吉田 英昭, 三浦 哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 )  55 ( 6 ) 1065 - 1065  2013年08月

Adipocyte lipid chaperone aP2 Is a secreted adipokine regulating hepatic glucose production

Haiming Cao, Motohiro Sekiya, Meric Erikci Ertunc, M. Furkan Burak, Jared R. Mayers, Ariel White, Karen Inouye, Lisa M. Rickey, Baris C. Ercal, Masato Furuhashi, Gürol Tuncman, Gökhan S. Hotamisligil

Cell Metabolism ( 5 )  17 ( 5 ) 768 - 778  2013年05月  [査読有り]

　概要を見る

Proper control of hepatic glucose production is central to whole-body glucose homeostasis, and its disruption plays a major role in diabetes. Here, we demonstrate that although established as an intracellular lipid chaperone, aP2 is in fact actively secreted from adipocytes to control liver glucose metabolism. Secretion of aP2 from adipocytes is regulated by fasting- and lipolysis-related signals, and circulating aP2 levels are markedly elevated in mouse and human obesity. Recombinant aP2 stimulates glucose production and gluconeogenic activity in primary hepatocytes in vitro and in lean mice in vivo. In contrast, neutralization of secreted aP2 reduces glucose production and corrects the diabetic phenotype of obese mice. Hyperinsulinemic-euglycemic and pancreatic clamp studies upon aP2 administration or neutralization demonstrated actions of aP2 in liver. We conclude that aP2 is an adipokine linking adipocytes to hepatic glucose production and that neutralizing secreted aP2 may represent an effective therapeutic strategy against diabetes. © 2013 Elsevier Inc.

DOI PubMed

急激な血糖悪化を契機に偶然発見され、多腺性内分泌腫瘍症1型が疑われた1例

菅原 浩仁, 小笠原 惇, 伊藤 孝仁, 田中 希尚, 古橋 眞人, 下重 晋也, 丹野 雅也, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  56 ( 1 ) 41 - 41  2013年01月

Histopathology of the pancreas in fulminant type 1 diabetes after 23-year follow-up: a case report

Tatsuya Sato, Takayuki Miki, Naoto Murakami, Yoshihiko Hirohashi, Hidemichi Kouzu, Masato Furuhashi, Masaya Tanno, Satoshi Yuda, Shigeyuki Saitoh, Tadashi Hasegawa, Tetsuji Miura

PATHOLOGY INTERNATIONAL ( WILEY-BLACKWELL )  62 ( 12 ) 827 - 829  2012年12月  [査読有り]

DOI PubMed

Elevation of Fatty Acid-Binding Protein 4 Is Predisposed by Family History of Hypertension and Contributes to Blood Pressure Elevation

Hideki Ota, Masato Furuhashi, Shutaro Ishimura, Masayuki Koyama, Yusuke Okazaki, Tomohiro Mita, Takahiro Fuseya, Tomohisa Yamashita, Marenao Tanaka, Hideaki Yoshida, Kazuaki Shimamoto, Tetsuji Miura

AMERICAN JOURNAL OF HYPERTENSION ( OXFORD UNIV PRESS )  25 ( 10 ) 1124 - 1130  2012年10月  [査読有り]

　概要を見る

BACKGROUND Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, and atherosclerosis. However, little is known about the role of FABP4 in essential hypertension. METHODS We first examined serum FABP4 concentrations in 18 normotensives (NT) and 30 nontreated essential hypertensives (EHT). The EHT were divided into 18 insulin-sensitive EHT (EHT-S) and 12 insulin-resistant EHT (EHT-R) based on their insulin-sensitivity index, the M value, determined by the hyperinsulinemic euglycemic clamp technique. In the second study, we determined FABP4 levels in 30 young NT men with or without a family history of hypertension (FH+ and FH-, respectively; n = 15 each). RESULTS Serum FABP4 level was significantly higher in the EHT-R than in the NT, whereas elevation of FABP4 level in the EHT-S was not statistically significant. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, and triglycerides and negatively correlated with the M value. FABP4 level was an independent predictor of mean arterial pressure after adjustment of age, gender, and adiposity. The FH+ group had a significantly lower level of M value and higher level of FABP4 than did the FH(-)group, and FABP4 concentration was an independent determinant of the M value. CONCLUSIONS FABP4 contributes to blood pressure elevation and atherogenic metabolic phenotype in hypertensives, and the elevation of FABP4 is predisposed by a family history of hypertension.

DOI PubMed

妊娠関連発症劇症1型糖尿病の発症後23年が経過し、日和見感染症で死亡した一剖検例

村上 直人, 佐藤 達也, 廣橋 良彦, 神津 英至, 古橋 眞人, 湯田 聡, 三木 隆幸, 斎藤 重幸, 土橋 和文, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  55 ( 10 ) 827 - 827  2012年10月

Angiotensin II receptor activation in youth triggers persistent insulin resistance and hypertension-a legacy effect?

Nobuhiko Togashi, Takuto Maeda, Hideaki Yoshida, Masayuki Koyama, Marenao Tanaka, Masato Furuhashi, Kazuaki Shimamoto, Tetsuji Miura

HYPERTENSION RESEARCH ( NATURE PUBLISHING GROUP )  35 ( 3 ) 334 - 340  2012年03月  [査読有り]

　概要を見る

Although the involvement of angiotensin II (Ang II) in insulin resistance and hypertension has been established, the temporal relationships between Ang II receptor activation and changes in insulin sensitivity and blood pressure are not clear. To better understand this issue, we infused rats with Ang II (200 ng kg(-1) min(-1)) or vehicle for 4 weeks and assessed the residual effects after the discontinuation of the infusion on blood pressure, insulin sensitivity and tissue parameters of inflammation. Four weeks after the discontinuation of the Ang II infusion, the blood pressure was higher by 12.8mmHg, and insulin sensitivity as determined by a euglycemic hyperinsulinemic glucose clamp was reduced (glucose infusion rate: 11.1+/-0.7 vs. 17.6+/-0.5mg kg(-1) min(-1)) in the Ang II-treated group compared with controls. The persistent hypertension and insulin resistance were associated with greater than two-fold increases in macrophage chemoattractant protein-1, tumor necrosis factor-alpha and thiobarbituric acid-reactive substrates in the soleus muscle. Furthermore, total and activated forms of Rac-1, a regulatory subunit of the NADPH oxidase complex, were increased by 144 +/- 14% and 277 +/- 82%, respectively, in the skeletal muscle of Ang II-treated rats. These residual effects after Ang II infusion were all attenuated by the co-administration of tempol, a free radical scavenger, or candesartan with Ang II. The effects of candesartan were not mimicked by hydralazine at an equidepressant dose. These findings suggest that Ang II receptor activation in youth triggers the upregulation of inflammatory cytokines and the production of reactive oxygen species, thereby inducing later insulin resistance and hypertension. Hypertension Research (2012) 35, 334-340; doi: 10.1038/hr.2011.206; published online 1 December 2011

DOI PubMed

Serum Fatty Acid-Binding Protein 4 Is a Predictor of Cardiovascular Events in End-Stage Renal Disease

Masato Furuhashi, Shutaro Ishimura, Hideki Ota, Manabu Hayashi, Takahiro Nishitani, Marenao Tanaka, Hideaki Yoshida, Kazuaki Shimamoto, Goekhan S. Hotamisligil, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE )  6 ( 11 ) e27356  2011年11月  [査読有り]

　概要を見る

Background: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality. Methods and Results: Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2 +/- 30.5 ng/ml) was significantly higher than that in males (315.8 +/- 30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05-25.31). Conclusion: These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

DOI PubMed

Lipid chaperones and metabolic inflammation.

Furuhashi M, Ishimura S, Ota H, Miura T

International journal of inflammation   2011   642612  2011年  [査読有り]

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Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium

Marenao Tanaka, Hideaki Yoshida, Masato Furuhashi, Nobuhiko Togashi, Masayuki Koyama, Satoshi Yamamoto, Tomohisa Yamashita, Yusuke Okazaki, Shutaro Ishimura, Hideki Ota, Tadashi Hasegawa, Tetsuji Miura

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  50 ( 23 ) 2877 - 2887  2011年  [査読有り]

　概要を見る

Objective We examined the hypothesis that renal congestion is responsible for the decline in renal function in patients with heart failure (HF) via tubulointerstitial inflammation. Methods First, in a longitudinal study, we retrospectively examined the relationship between cardiac functions and the decline of renal function during a period of 6.4 +/- 3.2 years in 20 patients who had a left ventricular ejection fraction of <40% and an estimated glomerular filtration ratio (eGFR) of <60 mL/min/1.73 m(2). Second, we compared the renal histology in autopsy cases of HF-induced renal dysfunction (HF-RD), cases of nephrosclerosis (NSC) and cases of neither RD nor HF (controls) in a cross-sectional study. Third, we retrospectively examined renal function in HF patients with predominantly right, but not left, ventricular dysfunction. Results eGFR decreased at 9.4 +/- 4.6%/year in the cohort of the longitudinal study. The rate of eGFR decline was correlated with blood pressure and with diameter of the inferior vena cava (IVCd) (r=0.5) measured at the initial work-up. Multivariate analysis indicated that the IVCd is an independent determinant of decline of eGFR in HF. In the cross-sectional study, fibrosis, Rac1 expression, protein nitrosylation, and number of CD68-positive cells were increased in the tubulointerstitium in both cases of HF-RD and NSC. Peritubular capillaries in HF-RD were dilated by 35% without any change in density compared with those in the controls. In right sided HF, the reduction of IVCd after treatment was associated with improvement of eGFR. Conclusion Venous congestion may contribute to HF-induced deterioration of renal function by augmenting oxidative stress-mediated inflammation in the tubulointerstitium.

DOI PubMed

腎に限局したIgG4関連疾患の一例

岡崎 雄介, 田中 希尚, 山本 諭, 山下 智久, 萩原 誠, 富樫 信彦, 古橋 眞人, 吉田 英昭, 三浦 哲嗣, 山本 元久, 苗代 康可

日本腎臓学会誌 ( (一社)日本腎臓学会 )  52 ( 6 ) 704 - 704  2010年08月

慢性心不全による腎障害進展の機序にはうっ血性障害が関与する

田中 希尚, 吉田 英昭, 富樫 信彦, 山下 智久, 岡崎 雄介, 石村 周太郎, 茂庭 仁人, 古橋 眞人, 島本 和明

日本腎臓学会誌 ( (一社)日本腎臓学会 )  52 ( 3 ) 285 - 285  2010年05月