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Kidney Week

Abstract: FR-PO0149

Mechanisms of Diet-Induced Kidney Protection: A Translational Research Approach

Session Information

  • AKI: Mechanisms - 2
    November 07, 2025 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Koehler, Felix C., Universitatsklinikum Koln, Cologne, NRW, Germany
  • Cukoski, Sadrija, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Lopes, Francisco José Calheiros Craveiro, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany
  • Knieps, Luisa, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Späth, Martin R., Universitatsklinikum Koln, Cologne, NRW, Germany
  • Hoyer-Allo, Karla Johanna Ruth, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Grundmann, Franziska, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Osterholt, Thomas, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Steiner, Joachim D., Universitatsklinikum Koln, Cologne, NRW, Germany
  • Antebi, Adam, Max-Planck-Institut fur Biologie des Alterns, Cologne, NRW, Germany
  • Beyer, Andreas, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany
  • Stippel, Dirk L., Universitatsklinikum Koln, Cologne, NRW, Germany
  • Benzing, Thomas, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Kann, Martin, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Kurschat, Christine E., Universitatsklinikum Koln, Cologne, NRW, Germany
  • Burst, Volker Rolf, Universitatsklinikum Koln, Cologne, NRW, Germany
  • Mueller, Roman-Ulrich, Universitatsklinikum Koln, Cologne, NRW, Germany
Background

A pivotal problem in aging-associated kidney disease is the elevated risk of acute kidney injury (AKI). Despite its considerable burden, effective therapeutic approaches are lacking. Interestingly, specific diets have shown an immense potential to prevent kidney damage in rodent models. However, the successful transfer to the clinic is still lagging behind, as the optimal diet for humans paired with the underlying molecular mechanisms remain elusive.

Methods

Five tailored dietary preconditioning protocols are examined in a rodent model of renal ischemia reperfusion injury (IRI) to quantify diet-induced kidney protection. To pave the way for a successful transfer to the clinic, we use a multi-layered omics approach in addition to single nucleus RNA sequencing to decipher shared mechanisms in diet-induced kidney protection. In parallel, beneficial dietary interventions are examined in a pilot study, the DILKID-Trial (NCT05709600), during living kidney donation to recapitulate common and conserved mechanism in man.

Results

Preconditioning with either a diet depleted in sulfur-containing amino acids (SR) or caloric restriction (CR) led to a significantly improved survival following AKI. None of these animals died within 72 hours after renal IRI, whilst this was the case for 50% of the non-preconditioned animals and kidney function remained normal in CR/SR mice. Our molecular analyses revealed unique dynamics in cysteine metabolism as an overlapping mechanism mediating diet-induced kidney protection. As to the DILKID-Trial, more than 50% of participants have been recruited to date. These kidney donors underwent the dietary regimens shown to be beneficial in the mouse model with no treatment-related adverse events. Biofluids and kidney biopsies samples were collected in all participants and are now prepared for molecular analysis using the same multi-layered omics platform.

Conclusion

CR/SR protect from IRI-induced kidney damage and show common and conserved metabolic mechanisms to achieve renal resilience. As CR/SR are feasible in humans our findings provide an important outlook towards novel protective strategies in the patient setting.

Funding

  • Private Foundation Support

Digital Object Identifier (DOI)