Tanaka Marenao, Yoshida Hideaki, Furuhashi Masato, Togashi Nobuhiko, Koyama Masayuki, Yamamoto Satoshi, Yamashita Tomohisa, Okazaki Yusuke, Ishimura Shutaro, Ota Hideki, Hasegawa Tadashi, Miura Tetsuji
The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
Intern Med. 2011;50(23):2877-87. doi: 10.2169/internalmedicine.50.5925. Epub 2011 Dec 1.
We examined the hypothesis that renal congestion is responsible for the decline in renal function in patients with heart failure (HF) via tubulointerstitial inflammation.
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.
Venous congestion may contribute to HF-induced deterioration of renal function by augmenting oxidative stress-mediated inflammation in the tubulointerstitium.
我们检验了这样一个假设，即肾淤血通过肾小管间质炎症导致心力衰竭（HF）患者肾功能下降。
首先，在一项纵向研究中，我们回顾性研究了20例左心室射血分数<40%且估计肾小球滤过率（eGFR）<60 mL/min/1.73 m²的患者在6.4±3.2年期间心功能与肾功能下降之间的关系。其次，在一项横断面研究中，我们比较了HF引起的肾功能障碍（HF-RD）尸检病例、肾硬化（NSC）病例以及既无肾功能障碍也无HF的病例（对照组）的肾脏组织学。第三，我们回顾性研究了以右心室功能障碍为主而非左心室功能障碍的HF患者的肾功能。结果在纵向研究队列中，eGFR以每年9.4±4.6%的速度下降。eGFR下降率与血压以及初始检查时测量的下腔静脉直径（IVCd）相关（r = 0.5）。多变量分析表明，IVCd是HF患者eGFR下降的独立决定因素。在横断面研究中，HF-RD和NSC病例的肾小管间质中纤维化、Rac1表达、蛋白质亚硝化以及CD68阳性细胞数量均增加。与对照组相比，HF-RD患者的肾小管周围毛细血管扩张了35%，密度无变化。在右心HF中，治疗后IVCd的降低与eGFR的改善相关。
静脉淤血可能通过增强肾小管间质中氧化应激介导的炎症，导致HF引起的肾功能恶化。
