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An Immature Murine Model of Reversible Unilateral Ureteral Obstruction
Published on: April 4, 2025
An animal model of calcium oxalate urolithiasis based on a cyclooxygenase 2 selective inhibitor
Byong Chang Jeong1, Min Young Park, Cheol Kwak
1Department of Urology, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, 28, Yongon-dong, Chongno-gu, 110-744 Seoul, Korea.
Abstract:
Our aim was to develop a stone-forming animal model involving renal tubular injury using a cyclooxygenase 2 selective inhibitor. Male Sprague-Dawley rats fed chow containing 3% sodium oxalate with or without 100 mg/kg celecoxib were compared to animals fed normal chow. Rats were killed after 2 or 4 weeks and the kidneys were harvested for morphological examination. Collections of 24-h urine were made before kidney harvest. After 2 weeks only a few crystals were observed in rats that received oxalate and celecoxib, but after 4 weeks more crystals were observed at the renal papilla than in rats that received only oxalate. Few crystals were found in rats fed normal chow with or without celecoxib. The urinary activities of gamma-glutamyl transpeptidase (GGT) were increased by celecoxib administration whereas creatinine clearance rates were unchanged. In rats fed oxalate, urinary oxalate excretion increased, but calcium excretion decreased. This model using a cyclooxygenase 2 selective inhibitor is a useful stone forming animal model involving mild renal tubular injury together with mild hyperoxaluria.
Insights
A novel animal model for kidney stone formation was developed using celecoxib, a cyclooxygenase 2 inhibitor. This model shows mild renal tubular injury and hyperoxaluria, aiding stone development research.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Kidney stone formation is a prevalent condition.
- Developing reliable animal models is crucial for studying stone pathogenesis and evaluating treatments.
- Cyclooxygenase 2 (COX-2) inhibitors have been implicated in modulating renal stone formation.
Purpose of the Study:
- To establish a novel stone-forming animal model.
- To investigate the role of COX-2 inhibition in renal tubular injury and stone development.
- To characterize the urinary and renal parameters in the developed model.
Main Methods:
- Male Sprague-Dawley rats were fed a diet containing 3% sodium oxalate.
- Celecoxib (100 mg/kg) was administered to a subset of rats receiving the oxalate diet.
- Kidney morphology and 24-hour urine collections were analyzed at 2 and 4 weeks.
Main Results:
- Celecoxib administration alongside oxalate diet led to increased crystal deposition at the renal papilla after 4 weeks compared to oxalate alone.
- Urinary gamma-glutamyl transpeptidase (GGT) levels increased with celecoxib, indicating renal tubular injury.
- Urinary oxalate excretion was elevated, while calcium excretion decreased in oxalate-fed rats.
Conclusions:
- The use of a selective cyclooxygenase 2 inhibitor effectively creates a stone-forming animal model.
- This model exhibits mild renal tubular injury and mild hyperoxaluria, mimicking key aspects of human kidney stone disease.
- The model serves as a valuable tool for further research into kidney stone pathogenesis and therapeutic strategies.
