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Abstract: FR-PO186

Renal Congestion Exacerbates Sepsis-Induced AKI in Mice

Session Information

  • AKI: Mechanisms - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Nakamura, Itaru, Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Kirita, Yuhei, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Tamagaki, Keiichi, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • Kusaba, Tetsuro, Kyoto Prefectural University of Medicine, Kyoto, Japan

Recent epidemiological studies demonstrated that renal congestion is a major factor in the development of renal dysfunction associated with heart failure. We previously established a novel unilateral renal congestion mouse model wherein the inferior vena cava was constricted between both renal veins, and reported its impact on the exacerbation of renal ischemia-reperfusion injury. However, the impact of renal congestion on septic AKI, the most common cause of AKI, is unclear.


We instigated sepsis via cecal ligation and puncture (CLP) in a unilateral renal congestion model. We comprehensively analyzed the pathophysiology of exacerbation of septic AKI by renal congestion, especially focused on the toll-like receptor (TLR) 2, a receptor of the innate immune system.


After the induction of CLP in the unilateral renal congestion model, the transient decline in blood pressure was observed at 3 and 6 hours after CLP. Ultrasonography revealed the persistent dilation of renal veins in the congested kidney for a duration extending up to 7 days post-CLP. Histological analysis at day 7 exhibited marked fibrosis in the group subjected to congestive heart failure + CLP, while qPCR assays indicated upregulation of fibrosis markers including Col1a1, Acta2, Tgfb1, and Fn1. At acute phase after procedures, extensive tubular damage with macrophage infiltration was noted in congestion + CLP group. qPCR demonstrated the upregulation of tlr2, in addition to inflammatory cytokines (Tnf, Ccl2). To further investigate the mechanistic insights focusing on the TLR2, we conducted CLP and renal congestion in TLR2-KO mice. Blood pressure transiently decreased at 3 and 6 hours after CLP, mirroring the response observed in WT mice. At 1 day post-CLP, tubular injury was exacerbated in the TLR2-KO group in comparison to the WT group, and qPCR analysis revealed an increase in Havcr1 expression and a decrease in Lrp2 expression, indicating that TLR2 might exert the inhibitive role on the exacerbation of sepsis-induced AKI by renal congestion.


This study using the combination of CLP and novel renal congestion model demonstrated the increased renal venous pressure may have contributed to the exacerbation of the AKI by inducing a reduction in renal perfusion following CLP, thereby implicating the involvement of TLR2 in this process.