ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

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
  • Späth, Martin R., Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Brodesser, Susanne, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Bohl, Katrin, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Kubacki, Torsten, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Kiefer, Katharina, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Koehler, Felix C., Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Grundmann, Franziska, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Schermer, Bernhard, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Benzing, Thomas, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Burst, Volker Rolf, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
  • Mueller, Roman-Ulrich, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany
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.