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, 30 (6), 1007-1023.e5

Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease


Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease

Jacob A Torres et al. Cell Metab.


Mild reduction in food intake was recently shown to slow polycystic kidney disease (PKD) progression in mouse models, but whether the effect was due to solely reduced calories or some other aspect of the diet has been unclear. We now show that the benefit is due to the induction of ketosis. Time-restricted feeding, without caloric reduction, strongly inhibits mTOR signaling, proliferation, and fibrosis in the affected kidneys in a PKD rat model. A ketogenic diet had a similar effect and led to regression of renal cystic burden. Acute fasting in rat, mouse, and feline models of PKD results in rapid reduction of cyst volume, while oral administration of the ketone β-hydroxybutyrate (BHB) in rats strongly inhibits PKD progression. These results suggest that cystic cells in PKD are metabolically inflexible, which could be exploited by dietary interventions or supplementation with BHB, representing a new therapeutic avenue to treat PKD.

Keywords: beta-hydroxybutyrate; ketogenic diet; ketosis; metabolic inflexibility; polycystic kidney disease.

Conflict of interest statement

Declaration of Interests

JT and TW are listed inventors on a provisional patent application filed by UCSB related to discoveries reported in this paper. TW is an inventor on a patent application by UCSB on a discovery unrelated to this paper. MM reports grants and consulting fees outside the submitted work from Otsuka Pharmaceuticals,Sanofi, and Chinook Therapeutics.

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