Kidney Week

Abstract: TH-OR047

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

Session Information

• Cystic Kidney Diseases: Genes, Mechanisms, Interventions
  November 02, 2017 | Location: Room 390, Morial Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Genetic Diseases of the Kidney

• 801 Cystic Kidney Diseases

Authors

• Torres, Jacob A., University of California, Santa Barbara, Goleta, California, United States

Jacob A. Torres, PhD

2017-Current: Post Doctoral Researcher, Weimbs Lab, University California Santa Barbara 2010-2017: Graduate Student Researcher, Weimbs Lab, University California Santa Barbara PhD, University California Santa Barbara 2017 B.S., University California Riverside 2010

• Broderick, Caroline M., University of California, Santa Barbara, Goleta, California, United States

Caroline M. Broderick,

• Kruger, Samantha, University of California, Santa Barbara, Goleta, California, United States

Samantha Kruger,

• Schimmel, Margaret F, University of California, Santa Barbara, Goleta, California, United States

Margaret F Schimmel,

• Weimbs, Thomas, University of California, Santa Barbara, Goleta, California, United States

Thomas Weimbs,

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