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Kidney Week

Abstract: TH-PO683

Ketogenic Dietary Interventions Ameliorate Disease Progression in a Rat Model of Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Torres, Jacob A., University of California Santa Barbara, Goleta, California, United States
  • Kruger, Samantha L., University of California Santa Barbara, Santa Barbara, California, United States
  • Amarlkhagva, Tselmeg, University of California Santa Barbara, Goleta, California, United States
  • Broderick, Caroline M., University of California Santa Barbara, Goleta, California, United States
  • Sahu, Alyssa, University of California Santa Barbara, Santa Barbara, California, United States
  • Weimbs, Thomas, University of California Santa Barbara, Santa Barbara, California, United States
Background

PKD cells have recently been shown to have an altered metabolism favoring aerobic glycolysis similar to the Warburg effect in cancer. Possible glucose dependency may provide an opportunity for the treatment of PKD by dietary interventions. We and others recently showed that a mild reduction in food intake strongly inhibits disease progression in PKD mouse models. Here we tested the hypothesis that these beneficial effects are due to ketosis caused by intermittent starvation rather than caloric restriction per se.

Methods

The Han:SPRD rat model of PKD was utilized to test the effects of time restricted feeding and a ketogenic diet, respectively, and on the progression of PKD. For time-restricted feeding, animals were given access to normal chow ad libitum for 8 hours per day. A ketogenic diet consisting of ~80% dietary fat administered ad libitum without time-restriction.

Results

Animals treated with either a ketogenic diet or a time-restricted feeding regime consumed comparable calories to ad libitum controls and showed a significant decrease in markers of disease progression including a decrease in fibrosis, 2-kidney to bodyweight, cystic index, markers of proliferation, and mTOR activity.

Conclusion

Dietary interventions that lead to ketogenesis significantly attenuate disease progression in the Han:SPRD rat model of PKD. Mechanistically, this may be due to the lack of glucose availability in ketosis. Alternatively, or in addition, the ketone body beta-hydroxybutyrate (BHB) is known to regulate several signaling pathways involved in PKD, including mTOR, and may directly influence cell growth and proliferation of cystic cells. These data taken together suggest that safe and feasible dietary interventions may be effective PKD patients.

Funding

  • Private Foundation Support