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Kidney Week

Abstract: FR-PO158

The Effects and Mechanism of Circadian Rhythm on Contrast-Induced Renal Injury

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

Authors

  • Yang, Shuqing, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • Jiang, Lei, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
  • Yang, Junwei, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Background

The circadian clock of mammals regulates various life activities. As an important metabolic organ in the body, the kidney exhibits a certain diurnal pattern in glomerular filtration function and ion transport of renal tubules. In view of the huge basic population of using contrast agents for diagnosis and treatment, as well as the potential long-term risks of renal diseases, contrast-induced acute kidney injury (CI-AKI) is a clinical problem that cannot be ignored. Although the pathogenesis of CI-AKI has been partially understood, the role and mechanism of circadian rhythm in contrast agent renal injury is still unknown.

Methods

The study retrospectively analyzed 33 patients undegoing percutaneous coronary angiography and coronary angioplasty in the cardiovascular center of our hospital from October 2020 to June 2022. In addition, all the mice were injected with 10 g/kg Iohexol through the tail vein at ZT0 or ZT12, respectively and sacrificed 24 hours later.

Results

The change of serum neutrophil gelatinase-associated lipocalin (NGAL) in the morning group (7:00~13:00) was higher than that of the afternoon group (13:00~20:00). The injection of Iohexol at ZT0 had almost no significant effects on the renal tissue of mice. While the injection of Iohexol at ZT12 increased the expression of kidney injury molecule 1 (KIM1), NGAL and lipid peroxidation products and reduced the expression of glutathione peroxidase 4. Knockdown of Clock in primary proximal renal tubular cells decreased the expression of Nrf2 and its downstream antioxidant target genes, while over-expression of Clock restored the expression of Nrf2. Finally, 4-octyl itaconate was intraperitoneal injected to upregulate the expression of NRF2 at ZT12, which alleviated the renal tubular injury caused by Iohexol.

Conclusion

The study shows the circadian clock regulates NRF2 mediated antioxidant response, which in turn leads to diurnal differences in contrast-induced renal injury.

Funding

  • Government Support – Non-U.S.