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Abstract: SA-PO989

SAMP1/YitFc as an Enteric Hyperoxaluria Mouse Model

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Zaidan, Nadim, NYU Langone Health, New York, New York, United States
  • Ho, Melody, NYU Langone Health, New York, New York, United States
  • Nazzal, Lama, NYU Langone Health, New York, New York, United States
Background

Enteric hyperoxaluria (EH) is a consequence of increased absorption of dietary oxalate secondary to fat malabsorption. Inflammatory bowel diseases, especially Crohn’s disease, are one of the most prevalent conditions causing EH. This hyperoxaluric state accounts for the increased incidence of kidney stones in this population. Urinary oxalate was also linked with the progression of chronic kidney disease. SAMP1 is a mouse model that spontaneously develops ileitis and AKR is its closest genetic relative. We hypothesized that SAMP1 mice will develop an EH phenotype.

Methods

This study assessed the impact of fat and oxalate-enriched diets in mice with and without ileitis. Two outcomes were evaluated: urinary oxalate and kidney function by measuring plasma creatinine. We fed 7-10 weeks old male SAMP1 and AKR mice with increasing amounts of dietary fat every two weeks (10%, 45%, and 60%) without oxalate. This was followed by the addition of 1% oxalate (Ox) to the diet and a parallel decrease in dietary fat.

Results

At the start of the study, UOx levels were comparable in the AKR and SAMP1 mice (10.1±1.46 µmol/L for SAMP1 vs 8.7±0.62 µmol/L for AKR, p=0.09). Increasing dietary fat did not affect UOx in either group, however, the addition of Ox in the diet led to a disproportional increase in UOx in SAMP1 mice as compared to AKR. On a 60% fat + 1% Ox, UOx levels were 27.3±2.55 µmol/L in SAMP1 mice vs 24.3±1.45 µmol/L in AKR (p=0.05). On 10% fat + 1% Ox at the end of the study, UOx from the SAMP1 mice was significantly higher than UOx from AKR mice (123±9.55 µmol/L vs 48.9±7.48 µmol/L (p<0.001). Plasma creatinine (PCr) was 17.5% higher in SAMP1 mice compared with AKR mice at baseline (p<0.01) and at sacrifice, PCr concentration were 70% higher in the SAMP1/YitFc compared to its control population (p<0.001).

Conclusion

We were able to establish the presence of the EH phenotype in the SAMP1 mouse model. We also witnessed the development of kidney injury, highlighting the nephrotoxicity of high UOx levels. The next steps will involve the characterization of the factors causing the increased absorption of dietary oxalate and the enteric hyperoxaluria phenotype (intestinal inflammation, gut permeability, oxalate transporter epithelial expression, and gut microbiome differences).

Funding

  • NIDDK Support