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Integrating animal science and human medicine: development of a novel porcine model for calcium oxalate stone formation
Increased collaboration between animal science departments and medical schools has been highly encouraged in recent years to enhance research funding competiveness. Development of animal models for investigating human health problems has been pivotal for the discovery of treatments for many life-threatening human illnesses. A team of researchers from the Department of Animal and Food Sciences at Texas Tech University and the Texas Tech University Health Sciences Center collaborated to develop a porcine model for use in the study and treatment of human calcium oxalate stone formation. Porcine were chosen as the model as they are the most congruent mammal to humans, both anatomically and physiologically, for the study of kidney stone disease. Male, Large White-Chester crossbred pigs (n = 16; 19 kg initial BW) were assigned to one of the following seven treatments: 1) 0.8% ethylene glycol administered in drinking water (EG) and 2 µg/kg BW vitamin D dissolved in syrup (Vit. D); 2) EG + 100 mg/kg BW ammonium chloride dissolved in syrup (AC); 3) EG + 5 mg/kg BW gentamicin intramuscularly 3 times/wk (GENT); 4) EG + 0.5 mg/kg BW Lasix dissolved in syrup; 5) EG + Vit. D + AC; 6) EG + Vit. D + GENT; 7) control. Treatments were administered for 28 d; blood was collected and renal panels were obtained on d 0, 14, and 28. Urine was collected on d 0, 14, and 28 and analyzed for pH, Ca, citrate, oxalate, creatinine and P. Renal and bladder ultrasound was conducted intermittently throughout the 28-d period. Animals were euthanized at the end of the study for collection of renal tissue for gross and microscopic analysis of crystal stone formation and inflammation. No crystal deposition was observed in control animals; however, all other treatments developed calcium oxalate stones, confirmed by histopathological analysis of hematoxyin and eosin staining, fluorescent microscopy and stone analysis by infrared spectrum. All treatment combinations examined in this study successfully induced stone formation in pigs. Of the treatment combinations, EG + Vit. D provided the most straightforward model for inducing kidney stone formation and is one that can be employed to study kidney stone disease and mitigation in humans.
Keywords: Animal Model, Animal Science, Human Medicine