Minipump induced hyperoxaluria and crystal deposition in rats: a model for calcium oxalate urolithiasis.

OBJECTIVE

Unraveling the mechanisms leading to clinically active calcium oxalate (CaOx) stone disease and the development of effective medical therapies to treat it have been hampered by the lack of appropriate animal models. To address this problem we developed a model of hyperoxaluria and calcium oxalate crystal deposition by implanting osmotic minipumps subcutaneously into male rats, that is minipump induced hyperoxaluria and crystal deposition in rats.

METHODS

Male Harlan-Sprague Dawley rats (225 to 290 gm) were implanted subcutaneously with 1-week 2 ml osmotic minipumps containing 1.5 M potassium oxalate (360 microM KOx/24 hours, [KOx-trt], 11) or phosphate buffered saline (PBS-trt, 9) on days 1 and 7. The 24-hour urine collections were performed on days 0, 4, 7, 11 and 14. Data were analyzed by ANOVA and Tukey's HSD. Urinary crystals were analyzed by light microscopy. Kidneys were harvested on day 14 and processed for light and polarizing microscopy, and RNA analysis.RESULTS Mean overall creatinine excretion +/- SEM (PBS-trt 107 +/- 7 and KOx-trt 123 +/- 6 microM/24 hours, p >0.07) and day 14 serum creatinine (PBS-trt 83 +/- 4 and KOx-trt 83 +/- 5 microM, p >or=0.9) were similar in the 2 treatment groups. Overall urinary volume (PBS-trt 11.3 +/- 0.8 and KOx-trt 18.0 +/- 1.5 ml/24 hours, p

CONCLUSIONS

The model of minipump induced hyperoxaluria and crystal deposition in rats reliably induces hyperoxaluria, CaOx crystalluria and CaOx crystal deposition. These characteristics make it an appropriate model for investigations of the effects of OX on renal physiology as well as investigating the efficacy of new therapeutics.