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Abstract: PO1265

A Combination Therapy with Two Dietary Supplements Acting on Different Mechanisms Ameliorates Disease Progression in a Rat Model of Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Torres, Jacob A., University of California Santa Barbara, Santa Barbara, California, United States
  • Asplund, David Allan, University of California Santa Barbara, Santa Barbara, California, United States
  • Kroes, Bradley Christian, University of California Santa Barbara, Santa Barbara, California, United States
  • Holznecht, Nickolas J., University of California Santa Barbara, Santa Barbara, California, United States
  • Amarlkhagva, Tselmeg, University of California Santa Barbara, Santa Barbara, California, United States
  • Rebello, Juliette R., University of California Santa Barbara, Santa Barbara, California, United States
  • Weimbs, Thomas, University of California Santa Barbara, Santa Barbara, California, United States
Background

Recently, our lab reported that dietary interventions to induce ketosis ameliorate disease progression PKD animal models, and that this effect involves the natural ketone beta-hydroxybutyrate (BHB). Additionally, we have recently shown that renal microcrystals exacerbate disease progression in PKD models. We now show that a combination of citrate and BHB effectively inhibits PKD progression. These compounds act on separate mechanisms, synergistically preventing cyst formation and cyst growth in young rats. In adult rats, the combination treatment leads to a partial reversal of existing renal cystic disease.

Methods

Juvenile and adult Han:Sprague-Dawley rats were treated with BHB, citrate or in combination via drinking water for 5 or 4 weeks respectively, then sacrificed and analyzed for changes in cystic burden and markers of disease progression. Additonally, rats were placed in metabolic cages to assess changes in urine parameters.

Results

Administration of either BHB or citrate alone in the drinking water effectively ameliorates PKD progression in a rat model. Combining BHB and citrate produced a synergistic effect. Cystogenesis and cyst growth were inhibited in juvenile animals. In adult animals with pre-existing renal cystic disease, the treatment leads to partial disease regression. We also find that administration of excess sodium and potassium alone, at doses that would be provided from the salts of citrate and BHB, lead to a worsening of PKD in our rat model.

Conclusion

The beneficial effects of ketosis are mimicked by administration of BHB in the drinking water and are consistent with a number of groups findings suggesting an underlying metabolic defect in PKD. Our other recent findings suggest excessive renal crystal burden leads to accelerated disease progression in PKD models. Renal crystal formation can be prevented by administration of citrate to both chelate calcium and raise urinary pH. These results are of high clinical significance because BHB and citrate are widely available and classified as safe dietary supplements. These results suggest that a combination of widely available and generally safe dietary supplements, when appropriately formulated, demonstrate high promise for supporting kidney health in PKD.

Funding

  • Other NIH Support