期刊
KIDNEY INTERNATIONAL
卷 101, 期 3, 页码 551-562出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2021.11.015
关键词
acute kidney injury; blood flow speed; Nuclear Factor-kappa B; renal congestion
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20K08640]
- Grants-in-Aid for Scientific Research [20K08640] Funding Source: KAKEN
Heart failure patients with kidney failure have increased kidney venous pressure and upregulated endothelial NF-kappa B signaling, which synergistically worsen kidney injury.
Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-kappa B (NF-kappa B) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was cancelled by inhibition of NF-kappa B signaling. Pharmacological inhibition of NF-kappa B for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow
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