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: TH-OR047

A Ketogenic Diet Slows Disease Progression in a Rat Model of Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Torres, Jacob A., University of California, Santa Barbara, Goleta, California, United States
  • Broderick, Caroline M., University of California, Santa Barbara, Goleta, California, United States
  • Kruger, Samantha, University of California, Santa Barbara, Goleta, California, United States
  • Schimmel, Margaret F, University of California, Santa Barbara, Goleta, California, United States
  • Weimbs, Thomas, University of California, Santa Barbara, Goleta, California, United States
Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a slowly progressing, life-threatening disease wherein normal healthy kidney tissue is replaced with fluid-filled cysts, decreasing renal function and leading to eventual renal failure. Cyst-lining cells have been shown to exhibit a metabolic shift towards aerobic glycolysis which may be exploited as a therapeutic approach. We have recently demonstrated that a reduction of food intake leads to a decrease in disease progression in a mouse model of ADPKD but the exact mechanism remained to be elucidated.

Methods

Here we show that the reduced food intake regimen leads to a partial state of ketosis and increased levels of beta-hydroxybutyrate (BHB). To test whether ketosis, rather than caloric reduction per se, leads to inhibition of renal cyst growth we treated the Han:SPRD rat model of PKD with a ketogenic diet regimen fed ad libitum.

Results

The high-fat, ketogenic diet leads to strong ketosis, elevation of BHB and concomitant reduction in blood glucose levels. Remarkably, Han:SPRD rats on the ketogenic diet exhibit strongly reduced disease progression with marked reduction in their cystic phenotype including significant reductions in kidney/body weight ratio, cystic index, proliferation and fibrosis.

Conclusion

These results suggest that cyst-lining cells may be dependent on glucose as their main energy source and are unable to switch to the use of ketone bodies and fatty acids under conditions of ketosis. These findings raise the exciting possibility that ketogenic diets may be a viable therapy for ADPKD.

Funding

  • Private Foundation Support