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Kidney Week

Abstract: SA-PO562

The Protective Effect of Klotho Against Contrast-Associated AKI via the Anti-Oxidative Effect

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kong, Kyoung Hye, Ewha Womans University, Seoul, Korea (the Republic of)
  • Oh, Hyung Jung, Ewha Womans University, Seoul, Korea (the Republic of)
  • Ryu, Dong-Ryeol, Ewha Womans University, Seoul, Korea (the Republic of)
Background

Contrast-associated acute kidney injury (CA-AKI) is defined as AKI caused by the supplementation of iodinated contrast agents, and oxidative stress is one of its main factors. Klotho, an anti-aging gene, shows anti-oxidative activity and is expressed in renal tubular cells. We investigated the protective effect of klotho against CA-AKI via the anti-oxidative effect.

Methods

We used NRK-52E cell lines and iopamidol as the contrast agent. Experiments were performed after cell cultures were divided into one of three groups: the control, iopamidol, and iopamidol+recombinant klotho (rKL) groups. Moreover, the siRNA-mediated knockdown of klotho (siklotho) was also done to reveal the endogenous klotho effect. Cell viability and oxidative stress were measured, and real-time PCR and western blotting were performed. We also designed a CA-AKI mouse model with ketorolac, L-NAME and iopamidol, and performed experiments similar to our in vitro experiments.

Results

The viability of the NRK-52E cells significantly decreased, but oxidative stress significantly increased after 200 mgI iopamidol was supplemented for 1h compared to the controls. Protein and mRNA expressions of klotho also significantly decreased, while apoptotic markers (Bax/Bcl2, cleaved caspase3) increased significantly after iopamidol injection. However, the decrease in cell viability after iopamidol supplementation was significantly attenuated after the cells were exposed to rKL, and rKL mitigated the elevated apoptotic markers and oxidative stress under iopamidol injection. Additionally, the apoptotic markers and oxidative stress were significantly upregulated in the group of iopamidol-treated siklotho compared to the iopamidol-treated NTC group. Our in vivo study results showed similar trends to our in vitro experiments.

Conclusion

This study showed that klotho can protect against CA-AKI via the anti-oxidative effect. These findings provide new insight into the mechanisms behind the protective effect of klotho in CA-AKI.

Funding

  • Government Support - Non-U.S.