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Abstract: FR-OR10

Cysteine Catabolism Is a Central Player in Diet-Induced Renal Stress-Resistance

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Koehler, Felix C., Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Fu, Chun-Yu, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Späth, Martin R., Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Hoyer-Allo, Karla Johanna Ruth, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Bohl, Katrin, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Goebel, Heike, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Lackmann, Jan-Wilm, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Grundmann, Franziska, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Osterholt, Thomas, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Gloistein, Claas, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Steiner, Joachim D., Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Antebi, Adam, Max-Planck-Institut fur Biologie des Alterns, Koln, Nordrhein-Westfalen, Germany
  • Benzing, Thomas, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Schermer, Bernhard, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Burst, Volker Rolf, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
  • Mueller, Roman-Ulrich, Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
Background

Caloric restriction (CR) protects from acute kidney injury (AKI) in rodents. Translation of CR to the clinic is complex. Novel targeted dietary regimens modulating the dietary composition of macro- and micronutrients promise similar protective effects and increased translatability.

Methods

Six targeted dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chain amino acids (BCAA), SR80/100, two dietary regimens restricting sulfur containing amino acids (SAA) by 80 percent (SR80) or entirely (SR100), and CR - were systematically examined in a murine model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced kidney protection. Shared mechanisms of dietary achieved renal resilience were deciphered using targeted metabolite and proteome profiling and confirmed in a human cohort of cardiac surgery patients adhering to a low-SAA diet.

Results

FMD, SR80/100 and CR efficiently protected from IRI-induced AKI quantified by kidney function, tissue damage and survival rates in mice. Preconditioning with KD yielded moderate benefits after IRI, whereas BCAA failed to protect from renal ischemic damage. Targeted metabolite and proteome profiling revealed overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a pivotal mechanism of kidney protection in response to FMD, SR80/100 and CR identifying sulfite as its central component. These diet-induced metabolic adaptions were confirmed in humans consuming a low-SAA diet.

Conclusion

FMD, SR80/100 and CR protect from IRI-induced AKI and show common metabolic patterns regarding cysteine catabolism. Importantly, these metabolic changes can be recapitulated in patients undergoing a low-SAA diet indicating a conserved metabolic response. Since FMD and low-SAA diets are feasible in humans our findings provide an important outlook towards novel protective strategies in the patient setting.

Funding

  • Private Foundation Support