Brandon P Trojan1, Sara J Trojan2, Andrew Navetta1, Bryce Staches1, Bryan Sutton3, Stephanie Filleur1,4, Thomas Nelius5. 1. Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 7260, Lubbock, TX, 79430-7260, USA. 2. Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX, USA. 3. Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX, USA. 4. Department of Immunology and Molecular Biology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. 5. Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, Stop 7260, Lubbock, TX, 79430-7260, USA. thomas.nelius@ttuhsc.edu.
Abstract
BACKGROUND: Mechanisms for calcium-based stone formation are not clearly delineated. Porcine are the most anatomically and physiologically congruent mammal to humans. Our objectives were to develop a cost-effective and easily reproducible porcine model for the study of calcium-based nephrolithiasis. METHODS: Crossbred male pigs (n = 16) were assigned randomly to one of the following treatments: (1) control; (2) ethylene glycol (EG) + vitamin D (VD); (3) EG + ammonium chloride (AC); (4) EG + gentamicin (G); (5) EG + Lasix; (6) EG + VD + AC; (7) EG + VD + G. Treatments were administered for 28 days; blood and urine were collected on day 0, 14, and 28. At the endpoint of the study, renal tissue was collected for gross and microscopic analysis of crystal stone formation and inflammation. RESULTS: Stone-forming parameters were observed in serum and urine. For control versus all other treatments, by day 28, serum BUN and creatinine were less (P < 0.01), urinary creatinine, citrate and pH were greater (P < 0.01), and urinary oxalate was less (P < 0.01). Histopathological analysis of H&E staining and stone analysis revealed formation of calcium oxalate stones and crystal formation within the renal cortex and medulla for all animals except control. Nephrotoxicity was observed in one animal from treatment EG + G. CONCLUSIONS: The treatments explored in this experiment provided novel examples of cost-effective porcine models for the study of nephrolithiasis. EG + VD had the strongest indicators of nephrolithiasis without nephrotoxicity.
BACKGROUND: Mechanisms for calcium-based stone formation are not clearly delineated. Porcine are the most anatomically and physiologically congruent mammal to humans. Our objectives were to develop a cost-effective and easily reproducible porcine model for the study of calcium-based nephrolithiasis. METHODS: Crossbred male pigs (n = 16) were assigned randomly to one of the following treatments: (1) control; (2) ethylene glycol (EG) + vitamin D (VD); (3) EG + ammonium chloride (AC); (4) EG + gentamicin (G); (5) EG + Lasix; (6) EG + VD + AC; (7) EG + VD + G. Treatments were administered for 28 days; blood and urine were collected on day 0, 14, and 28. At the endpoint of the study, renal tissue was collected for gross and microscopic analysis of crystal stone formation and inflammation. RESULTS: Stone-forming parameters were observed in serum and urine. For control versus all other treatments, by day 28, serum BUN and creatinine were less (P < 0.01), urinary creatinine, citrate and pH were greater (P < 0.01), and urinary oxalate was less (P < 0.01). Histopathological analysis of H&E staining and stone analysis revealed formation of calcium oxalate stones and crystal formation within the renal cortex and medulla for all animals except control. Nephrotoxicity was observed in one animal from treatment EG + G. CONCLUSIONS: The treatments explored in this experiment provided novel examples of cost-effective porcine models for the study of nephrolithiasis. EG + VD had the strongest indicators of nephrolithiasis without nephrotoxicity.
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