Abstract: SA-PO0138
A Low-Lysine Diet Modulates Renal and Hepatic Amino Acid Transporter Expression in ADPKD
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Duyvestyn, Branden G., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Hallit, Emily, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Moran-Reyna, Aida, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Flournoy, Torrey, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Sedaka, Randee, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Saigusa, Takamitsu, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, characterized by kidney and liver cyst growth and eventual kidney failure. Most ADPKD cases result from mutations in PKD1. While gene mutations drive cystogenesis, environmental factors such as high-protein diet accelerate kidney cyst growth in mice. We have shown that an animal-based protein diet worsened disease severity compared to a plant-based protein diet in ADPKD mice. Animal-based protein has a higher lysine content relative to plant-based protein. We therefore hypothesized that a low-lysine diet would mitigate disease progression.
Methods
Adult conditional Pkd1 global knockout (KO) mice and floxed controls were fed isocaloric high-casein-based protein diets that were formulated with either high-lysine (HL) or low-lysine (LL) for 6 weeks and euthanized. Kidneys and livers were collected for histology, RT-PCR, western blot analysis and immunohistochemistry.
Results
Kidney cystogenesis was primarily driven by genotype with no significant dietary effect. However, kidney-weight to body-weight ratio (KW/BW) was significantly reduced in KO-LL compared to KO-HL mice despite similar BWs. In KO-LL kidneys, gene expression of lysine-shuttling amino acid transporters (Slc7a7, Slc7a9) and gluconeogenic metabolic regulator Pepck1 were increased. There were no differences in plasma creatinine, but injury marker Lcn2 increased in KO-HL compared to KO-LL mice in both kidney and liver. Western blot analysis of kidney y+LAT-1 (Slc7a7 protein) revealed no differences between KO-LL and KO-HL groups. KO-LL livers showed reduced expression of lysine transporter Slc7a2 relative to KO-HL mice. Immunohistochemistry revealed an absence of CAT-2 (Slc7a2 protein) in hepatic cyst-lining versus healthy epithelia, regardless of diet.
Conclusion
Six weeks of low-lysine diet did not reduce cystogenesis, but it attenuated KW/BW ratio and injury while modulating expression of metabolic and amino acid transporters in both the kidney and liver. Longer-term studies are needed to determine whether sustained lysine restriction impacts kidney cystogenesis.
Funding
- NIDDK Support