Abstract: FR-PO1016
Therapeutic Potential of Oxalobacter formigenes in CKD Development and Progression
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Xiong, Xiaozhong, NYU Langone Health, New York, New York, United States
- Zaidan, Nadim, NYU Langone Health, New York, New York, United States
- Cardozo, Lila, NYU Langone Health, New York, New York, United States
- Charytan, Amalya M., NYU Langone Health, New York, New York, United States
- Ho, Melody, NYU Langone Health, New York, New York, United States
- Mishra, Arnav, NYU Langone Health, New York, New York, United States
- Nazzal, Lama, NYU Langone Health, New York, New York, United States
- Ambersley, Safirya, NYU Langone Health, New York, New York, United States
Group or Team Name
- New York Institute of Technology College of Osteopathic Medicine.
Background
Cardiovascular events are the leading cause of death in chronic kidney disease (CKD) patients, but the mechanisms are poorly understood. Oxalate retention has been shown to induce systemic fibrosis and inflammation, contributing to CKD progression and cardiovascular complications in renal failure. Hydroxyproline is a common component of meats and a precursor of oxalate. Oxalobacter Formigenes (OxF) is a specialist oxalate degrader in the human intestines. We hypothesize that OxF colonization in CKD mice reduces oxalate levels and attenuates CKD progression and cardiovascular damage.
Methods
Twenty 5/6 nephrectomy (CKD) mice and 20 Sham-operated mice received a 1% hydroxyproline-supplemented diet for five months. 10 CKD and 10 Sham mice received one dose of OxF (1x109 CFU), and the other mice received culture medium as control. Mouse urine and blood were collected at different time points for measuring oxalate and creatine. All mice were sacrificed after five months, and their kidneys and hearts were harvested.
Results
Hydroxyproline supplementation induced kidney damage. Plasma oxalate and creatine level were increased in all mice. OxF treatment reduced plasma oxalate and creatine in both Sham and CKD groups. CKD mice had more severe inflammation and fibrosis in the kidney than Sham mice. OxF treatment ameliorated inflammation and fibrosis in both Sham and CKD mice. Perivascular fibrosis was found in the heart of CKD mice, but OxF-treated CKD mice displayed less perivascular fibrosis. RNA-seq of heart tissue revealed that the top altered genes and pathways in CKD compared to control mice were related to increased inflammation and fibrosis, decreased lipid metabolism, and increased lipid accumulation. However, OxF treatment reversed those pathways and genes altered in CKD control mice.
Conclusion
Hydroxyproline promoted CKD development and progression, likely through increased oxalate levels. OxF treatment attenuated CKD progression and ameliorated cardiovascular damage.
Funding
- NIDDK Support