Abstract: SA-PO0291
Developing the Novel Sorbent ZO as an Oral Gut Oxalate Binder: Therapeutic Implications for Hyperoxaluria, Hyperoxalemia, and Related Disorders
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
- Abdelhalim, Khalid A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Wang, Yanzhe, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Amirkhani Namagerdi, Asadoor A, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Alfuraiji, Narjes, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Mburu, David A, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Bai, Karoona, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ali, Bilal F, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Elsanousi, Nusiba, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Carr, David, HemoCleanse Technologies, Lafayette, Indiana, United States
- Ash, Stephen R., HemoCleanse Technologies, Lafayette, Indiana, United States
- Hassan, Hatim A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Kidney stones (KS) affect ~1 in 5 men and ~1 in 11 women and account for 1.3M ER visits and >$10B of annual costs. Recurrence rate is high, at 50% in 5 years and up to 80% in 10-20 years. 70-80% of KS are composed of calcium oxalate; small increases in urine oxalate significantly enhance KS risk. Oxalate also potentially contributes to CKD and its progression, CKD/ESRD-associated cardiovascular diseases, and poor kidney allograft survival. This emphasizes the need for plasma and urinary oxalate lowering therapies, which can be achieved by reducing gut oxalate absorption. Our collaborator from HemoCleanse showed the novel sorbent ZO (a hydroxide-loaded anion exchanger) to be effective at binding phosphate in the gut, leading to reduced serum and urinary phosphate levels in rats. Oxalate is a divalent anion, and we hypothesized ZO also bind oxalate in the gut, leading to reduced plasma and urinary oxalate levels.
Methods
The effects of ZO (6 g/Kg body weight) on plasma, urinary, and fecal oxalate levels were assessed in mice fed a high oxalate diet. Serum bicarbonate, urine pH, and pathological changes in gastrointestinal and renal tissues were also assessed.
Results
Compared to changes in Control mice, ZO reduced urinary oxalate excretion by ~20%, 19%, and 40% after 1, 2, and 3 weeks, respectively. ZO reduced serum oxalate by ~34% after 1 week. Free fecal oxalate concentration is remarkably reduced (~83-95%) by ZO over this 3-week period. ZO is expected to increase rather than decrease oxalate excretion and our findings indicate that oxalate binding by ZO is so strong that it is not available to be measured by our assay. ZO releases hydroxide when it binds oxalate, which can potentially lead to metabolic alkalosis if absorbed systemically. Serum bicarbonate and urine pH are similar in ZO-treated and Control mice, reflecting no or minimal absorption of the released hydroxide. Importantly, ZO has no significant toxic effects on gastrointestinal and renal tissues in preliminary studies.
Conclusion
We conclude that ZO lowers plasma and urinary levels in mice fed a high oxalate diet, likely by effectively binding oxalate in the gut as reflected by the remarkably reduced free fecal oxalate concentration.
Funding
- Private Foundation Support