Kidney vascular congestion exacerbates acute kidney injury in mice

Takashi Kitani, Kengo Kidokoro, Tomohiro Nakata, Yuhei Kirita, Itaru Nakamura, Kunihiro Nakai, Aya Yagi-Tomita, Tomoharu Ida, Noriko Uehara-Watanabe, Kisho Ikeda, Noriyuki Yamashita, Benjamin D. Humphreys, Naoki Kashihara, Satoaki Matoba, Keiichi Tamagaki, Tetsuro Kusaba

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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-κB (NF-κB) 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 decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB 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 velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.

Original languageEnglish
Pages (from-to)551-562
Number of pages12
JournalKidney International
Issue number3
StatePublished - Mar 2022


  • Nuclear Factor-κB
  • acute kidney injury
  • blood flow speed
  • renal congestion


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