Deterioration of Renal Function by Chronic Heart Failure is Associated with Congestion and Oxidative Stress in the Tubulointerstitium
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概要
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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 m2. 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.
著者
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Miura Tetsuji
The Second Department Of Internal Medicine Sapporo Medical College
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FURUHASHI Masato
The Second Department of Internal Medicine, Sapporo Medical University School of Medicine
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TOGASHI Nobuhiko
The Second Department of Internal Medicine, Sapporo Medical University School of Medicine
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Hasegawa Tadashi
Department Of Cardiovascular And Thoracic Surgery Hakodate Municipal Hospital
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Yamamoto Satoshi
The Second Department Of Internal Medicine Kansai Medical University
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Yamamoto Satoshi
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Tanaka Marenao
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Yoshida Hideaki
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Koyama Masayuki
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Yamashita Tomohisa
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Okazaki Yusuke
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Ishimura Shutaro
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Ota Hideki
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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Miura Tetsuji
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan
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