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Kidney Week

Abstract: TH-PO004

Kynureninase Is Essential for Protection from AKI by Caloric Restriction

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Hoyer-Allo, Karla Johanna Ruth, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Späth, Martin R., Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Grundmann, Franziska, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Koehler, Felix C., Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Schermer, Bernhard, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Benzing, Thomas, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Burst, Volker Rolf, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
  • Mueller, Roman-Ulrich, Dept. 2 of Internal Medicine, University of Cologne, Koeln, Germany
Background

Experimental work shows that preconditioning by caloric restriction (CR) or hypoxia (HP) prevents acute kidney injury (AKI) reliably. Recently, we have identified Kynu as one of the top gene candidates conveying organ protection in a transcriptome analysis of renal tissue after preconditioning. Here, we further characterize the impact of Kynu in a mouse model of renal ischemia-reperfusion-injury (IRI).

Methods

We generated a conventional Knockout (KO) of Kynu using CRISPR/Cas9 mediated genome editing and non-homologous end joining (NHEJ) in C57Bl6 mice. Following a functional and histological phenotyping, wildtype and KO mice were preconditioned by CR and subsequently were subject to IRI.

Results

Kynu encodes kynureninase, which represents a key player in tryptophan metabolism. We confirmed the knockout of our newly generated mouseline by immunoblot, immunhistochemistry and mass spectrometry. The basal phenotyping of the KO mice did not differ from that of wildtype mice (appearance, weight, kidney function, histology). Renal function as well as histological features of AKI 24h after IRI were similar in KO mice without preconditioning and wildtype mice. However, while wildtype mice were effectivly protected from AKI after CR, this effect was significantly diminished in the Kynu KO animals after CR.

Conclusion

The induction of Kynu is associated with HP and CR. Our results confirm the pivotal role of Kynu as a key player of preconditioning-mediated renal protection. Further investigations to determine the mechanistic features of Kynu are required now.