Kidney Week

Abstract: SA-PO0290

Enteric Hyperoxaluria Murine Model: Unveiling a Potential Role of Dietary Oxalate in Intestinal Toxicity

Session Information

• Bone and Mineral Metabolism: Basic Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• Jaber, Karim, NYU Langone Health, New York, New York, United States

Karim Jaber, MD, MS, MSc

• Mishra, Rashmi, NYU Langone Health, New York, New York, United States

Rashmi Mishra, PhD

• Xiong, Xiaozhong, NYU Langone Health, New York, New York, United States

Xiaozhong Xiong, MD

• Bui, Michelle L, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States

Michelle L Bui

• Knight, John, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States

John Knight, PhD

• Nazzal, Lama, NYU Langone Health, New York, New York, United States

Lama Nazzal, MD, MS

Background

In the U.S., over 50,000 Crohn's disease patients experience enteric hyperoxaluria (EH), leading to high urinary oxalate levels and an increased risk of kidney stones. We previously developed a murine ileitis-EH model, exploring the roles of dietary oxalate and fat in its pathophysiology. While oxalate toxicity has been studied in renal and cardiac cells, its impact on the GI tract remains unexplored. This study aims to investigate whether high dietary oxalate induces intestinal inflammation and enhances oxalate absorption in a mouse model of ileitis.

Methods

20-week-old SAMP1/YitFc mice were assigned to either a 1% sodium oxalate-supplemented diet or a normal chow oxalate-free diet (NC). Control AKR mice were fed the same diets. After 6 weeks on the respective diets, 24-h urine samples were collected for urinary oxalate (UOx) quantification. To quantify intestinal dietary oxalate absorption, mice were administered a single oral dose of 100 µg ¹³C₂-oxalate and 24-h urinary ¹³C₂-oxalate measured by IC/MS.Blood, ileum, and colon were collected.

Results

SAMP1 mice on the oxalate diet developed significant hyperoxaluria (Fig. 1) with a UOx to urinary creatinine (UCr) ratio of 1.71±0.41 mg/mg, significantly higher to the other groups (p-values <0.05). SAMP1 mice, regardless of diet, exhibited increased oxalate absorption (4.90 ± 1.3 % for Ox and 4.76 ± 2.9% for NC compared to 0.14 ± 0.1 % for AKR Ox and 0.14 ± 0.23 for AKR NC) (Fig. 2). TNF and IFN levels were not different in ileum between mice from the same phenotype fed different diets. Both groups of SAMP1 mice had acute kidney injury, as indicated by elevated plasma creatinine.

Conclusion

Our findings underscore the critical role of dietary oxalate and its bioavailability in developing hyperoxaluria in ileitis. However, it minimizes the risk of increased toxicity and intestinal permeability that could be attributed to the direct effect of oxalate. These results emphasize the need to further investigate EH as a multifactorial complex mechanism.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20256dh68sgm