Hydroxyproline-induced hyperoxaluria using acidified and traditional diets in the porcine model.
BACKGROUND
Swine models have proven useful for many different disease processes, especially for urologic research. In this study, we sought to create a model of hyperoxaluria in the adult sow by feeding hydroxyproline (HP). The development of an adult porcine model for calcium oxalate stone disease would represent a significant contribution to stone research as previous animal models have been developed only for rats and baby pigs.


METHODS
The experiment included a total of 12 multiparous, gestating sows (Large White x Landrace). Sows were randomly allotted to one of the two treatment groups. Treatments involved basal diets that were either control diet (CD) or acidogenic diet (AD). Urine was collected for 6 consecutive days. On days 1 and 2, each sow was fed 2 kg of the assigned basal diet (CD or AD). On days 3, 4, and 5, 200 g of L-hydroxyproline (Wilshire Technologies, Princeton, NJ) was added to each basal diet for all the 12 sows. The HP was evenly mixed with the basal diets before feeding. On day 6, each sow was fed the basal diet originally assigned without HP ( Fig. 1 ). Urine was collected for each entire 24-hour period to control for differences in the diurnal and postprandial variations in the renal handling of oxalate and glycolate.


RESULTS
The addition of HP to the diet increased urinary oxalate excretion. Overall, there was a 192% (CD) and 187% (AD) increase in urinary oxalate between days 1 and 3. The increase peaked on day 3 and gradually returned to baseline by day 6. Student's paired t-test was performed and it confirmed that oxalate on days 3 and 5 was significantly different than baseline (p = 0.009 and p = 0.03, respectively). Urinary glycolate also increased as a result of adding HP to the diet. Overall, there was a 12,340% (CD) and 14,400% (AD) increase in urinary glycolate between days 1 and 3. The increase peaked on day 3 and then declined, although remained more than 10 x greater than baseline at day 6. Student's paired t-test confirmed that glycolate levels on days 3, 5, and 6 were significantly different than baseline (p < 0.001, p = 0.01, and p = 0.03, respectively).


CONCLUSIONS
The role of oxalate in the formation of kidney stones cannot be understated. Medical prevention and management of calcium oxalate nephrolithiasis will require a comprehensive understanding of oxalate metabolism in humans. A model for human hyperoxaluria can be reliably created in the adult sow. Such a model is necessary to further our understanding of oxalate metabolism and ultimately aid in the prevention of calcium oxalate calculi.
Kaplon
Daniel M
DM
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792-7375, USA.
Penniston
Kristina L
KL
Darriet
Camille
C
Crenshaw
Thomas D
TD
Nakada
Stephen Y
SY
D000143:Acids / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006016:Glycolates / Q000652:urine; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006909:Hydroxyproline / Q000633:toxicity*; D006959:Hyperoxaluria / Q000139:chemically induced* / Q000652:urine; D010070:Oxalates / Q000652:urine; D034421:Sus scrofa
D000143:Acids; D006016:Glycolates; D010070:Oxalates; D006909:Hydroxyproline