Kidney Week

Abstract: FR-PO716

Betaine Supplementation Ameliorates Renal Disease Severity in Experimental ADPKD

Session Information

• Cystic Kidney Diseases: Clinical/Translational
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Tug, Ali Y., Mayo Clinic, Rochester, Minnesota, United States

Ali Y. Tug,

• Zhang, Song, Mayo Clinic, Rochester, Minnesota, United States

Song Zhang,

• Vuckovic, Ivan, Mayo Clinic, Rochester, Minnesota, United States

Ivan Vuckovic,

• Arroyo, Jennifer, Mayo Clinic, Rochester, Minnesota, United States

Jennifer Arroyo,

• Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States

Alfonso Eirin,

• Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States

Lilach O. Lerman,

• Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States

Peter C. Harris,

• Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States

Vicente E. Torres,

• Irazabal, Maria V., Mayo Clinic, Rochester, Minnesota, United States

Maria V. Irazabal,

Background

We have recently shown that kidney tissue levels of the methyl donor betaine and betaine dependent remethylation are lower in ADPKD, and correlate with disease severity. However, the effects of betaine supplementation have not been explored in ADPKD. We hypothesized that chronic betaine supplementation would increase renal betaine concentration and ameliorate disease progression in murine ADPKD.

Methods

One month old Pkd1 ^RC/RC mice were divided into three groups and started treatment with regular water or regular water supplemented with 1 or 2% betaine for 5 months (n=16 per group). All mice were euthanized at 6 months of age, and kidneys were harvested. Cystic index was determined from histological sections. ¹H-NMR-based metabolomics analysis was performed from kidney tissue, urine and plasma samples.

Results

One and 2% betaine supplementation increased plasma and tissue betaine concentrations (p<0.001), reduced kidney/body weight to 1.82 and 1.85 vs 2.25 (p<0.01), and cystic index to 11.1 and 9.4 vs 21.1 (p<0.01) (Fig. 1). Tissue betaine concentrations correlated inversely with kidney/body weight (R²=0.386, p<0.01). Metabolomics analysis from tissue and plasma identified significant differences in mitochondrial fatty acid oxidation and TCA cycle pathways among the groups.

Conclusion

Chronic betaine supplementation ameliorates disease severity in murine ADPKD possibly through improving mitochondrial function. These observations may represent a promising intervention from early stages of the disease.

Funding

• NIDDK Support