INVESTIGATIVE UROLOGY

A porcine model of calcium oxalate kidney stone disease
Mandel NS, Henderson JD Jr, Hung LY, Wille DF, Wiessner JH
From the Departments of Medicine and Surgery, Medical College of Wisconsin and Department of Veterans Affairs, Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin
J Urol. 2004; 171: 1301-3

• Purpose: The pig has been extensively used in biomedical research because of the similarities in organ structure and function to humans. It is desirable to have an animal model of oxaluria and urolithiasis with physiological, anatomical and nutritional characteristics that more closely resemble those of man. In this study we determined if feeding pigs trans-4-hydroxy-l-proline (HP) increased urine oxalate levels and if it would serve as a model for human hyperoxaluria and stone disease.
• Materials and Methods: Male Yorkshire-Durox cross-bred pigs were fed HP for up to 20 days. Urine was periodically collected and analyzed for oxalate levels and the presence of crystalluria. After 20 days of feeding the kidneys were removed and examined grossly and microscopically for indications of injury, crystal deposition and stone formation.
• Results: Feeding pigs 10% HP (weight per weight HP/food) produced hyperoxaluria, which reached a maximum and leveled off by day 6. Urine oxalate remained near this level until the study ended at 20 days regardless of the further increase in HP to 20% of the weight of the food. When the kidneys were removed and grossly examined, calcium oxalate encrustations were observed on multiple papillary tips. Histopathological observation of the papillary tissue showed tissue injury and crystal deposition.
• Conclusions: Pigs fed HP have hyperoxaluria and calcium oxalate crystalluria, and calcium oxalate papillary deposits form that may be precursors of kidney stones. The use of the pig as a model of human hyperoxaluria and stone formation should prove ideal for studies of these human diseases.
  
  
• Editorial Comment
  In addition to be an excellent animal model for surgical experimentation due to its extra and intra-renal anatomy similarities to humans (1,2) swine have also been shown to be a good model for clinical urological studies, including the formation and treatment of renal calculi.
  In this research study, the authors tested if feeding pigs with trans-4-hydroxy-l-proline HP would increase their urine oxalate levels and produce a model of hyperoxaluria and calcium oxalate stone disease. The addition of HP to the pig diet resulted in an increase in urine oxalate excretion. Urine oxalate levels appeared to reach the maximum level at day 6 for all 3 HP fed pigs. Increasing the HP in the feed up to 20% by feed weight resulted in no further increase in urine oxalate levels.
  The authors found no morphological changes in corticomedullary or papillary areas in control pigs, on the other hand, changes indicative of cellular injury were observed in HP fed pigs. These changes included diffuse corticomedullary interstitial fibrosis with tubular dilatation, oxalate crystal deposition in tubules and focal collecting duct epithelial cell necrosis with aggregates of calcium oxalate crystals located at the papillary tip in all HP fed pigs. All these findings clearly demonstrated the feasibility of pig use as a model of human hyperoxaluria and stone formation.

References
1. Evan AP, Connors BA, Lingeman JE, Blomgren P, Willis LR: Branching patterns of the renal artery of the pig. Anat Rec. 1996; 246: 217-22.
2. Sampaio FJB, Pereira-Sampaio MA, Favorito LA: The pig kidney as an endourologic model: anatomic contribution. J Endourol. 1998; 12: 45-50.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil