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  3. Bradykinin induces acute kidney injury after hypothermic circulatory arrest through the repression of the Nrf2-xCT pathway

Bradykinin induces acute kidney injury after hypothermic circulatory arrest through the repression of the Nrf2-xCT pathway

  • iScience. 2024 May 22;27(6):110075. doi: 10.1016/j.isci.2024.110075.
Jinzhang Li 1 2 3,  Meili Wang 4 3,  Maozhou Wang 1 2 3,  He Sang 1 2 3,  Wei Wang 4 3,  Ming Gong 1 2 3,  Hongjia Zhang 1 2 3
Affiliations

Affiliations

  • 1 Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
  • 2 Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
  • 3 Beijing Lab for Cardiovascular Precision Medicine, Beijing, China.
  • 4 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
PMID: 38868208 DOI: 10.1016/j.isci.2024.110075
Abstract

Postoperative acute kidney injury (AKI) is a common complication in patients undergoing deep hypothermic circulatory arrest (HCA); however, its underlying pathogenesis is unclear. In this study, we established a rat cardiopulmonary bypass model and demonstrated that hypothermia during HCA, rather than circulatory arrest, was responsible for the occurrence of AKI. By recruiting 56 patients who underwent surgery with HCA and analyzing the blood samples, we found that post-HCA AKI was associated with an increase in bradykinin. Animal experiments confirmed this and showed that hypothermia during HCA increased bradykinin levels by increasing Kallikrein expression. Mechanistically, bradykinin inhibited the Nrf2-xCT pathway through B2R and caused renal oxidative stress damage. Application of Icatibant, a B2R inhibitor, reversed changes in the Nrf2-xCT pathway and oxidative stress damage. Finally, Icatibant reversed hypothermia-induced AKI in vivo. This finding reveals the pathogenesis of AKI after HCA and helps to provide therapeutic strategy for patients with post-HCA AKI.

Keywords

health sciences; medicine; pathophysiology.

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