Kidney Week

Abstract: PO0441

Caloric Restriction Reduces the Pro-Inflammatory Eicosanoid 20-HETE to Protect from AKI

Session Information

• AKI: Novel Insights
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Hoyer-Allo, Karla Johanna Ruth, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Karla Johanna Ruth Hoyer-Allo, MD

• Späth, Martin R., Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Martin R. Späth,

• Brodesser, Susanne, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany

Susanne Brodesser,

• Bohl, Katrin, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany

Katrin Bohl,

• Kubacki, Torsten, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Torsten Kubacki,

• Kiefer, Katharina, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Katharina Kiefer,

• Koehler, Felix C., Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Felix C. Koehler,

• Grundmann, Franziska, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Franziska Grundmann,

• Schermer, Bernhard, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Bernhard Schermer,

• Benzing, Thomas, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Thomas Benzing,

• Burst, Volker Rolf, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Volker Rolf Burst,

• Mueller, Roman-Ulrich, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Roman-Ulrich Mueller,

Background

Acute kidney injury (AKI) is a frequent complication in the clinical setting and associated with significant morbidity and mortality. Preconditioning with short-term caloric restriction (CR) is highly protective against kidney injury in rodent ischemia-reperfusion-injury (IRI) models, but the underlying mechanisms are unknown hampering clinical translation. The aim of this work was to further characterize possible mechanisms of protective effects of preconditioning.

Methods

14-week-old male and female C57Bl6 wild-type mice underwent no preconditioning serving as a control group (CR) or four weeks of a calorie-restricted diet as a method of preconditioning prior to IRI. Afterwards, we compared control animals with animals after CR by phenotyping (histology, urea).

Results

We examined the molecular basis of CR-mediated protection to elucidate the principles of renal stress resistance. Analysis of an RNAseq dataset after CR identified Cyp4a12a – a cytochrome exclusively expressed in male mice - to be strongly downregulated after CR. Renal IRI robustly induced AKI in male mice and damage could be markedly attenuated by pre-treatment with CR. In females, the damage was significantly less pronounced and preconditioning with CR had only little effect. Tissue concentrations of the metabolic product of Cyp4a12a, 20-Hydroxyeicosatetraenoic acid (20-HETE), were significantly reduced by CR. Conversely, intraperitoneal supplementation of 20-HETE in preconditioned males partly abrogated the protective potential of CR.

Conclusion

Our findings provide an insight into the mechanisms underlying renal organ protection and implicate 20-HETE as a target of CR-based preconditioning. Understanding the mediators of preconditioning is an important pre-requisite for moving towards translation to the clinical setting.

Funding

• Government Support – Non-U.S.