Abstract: SA-OR030

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stone Formation in Genetic Hypercalciuric Stone-Forming Rats

Session Information

Category: Mineral Disease

  • 1204 Mineral Disease: Nephrolithiasis

Authors

  • Krieger, Nancy S., Univ. of Rochester, Rochester, New York, United States
  • Asplin, John R., Litholink Corp, Chicago, Illinois, United States
  • Granja, Ignacio, Litholink Corp, Chicago, Illinois, United States
  • Ramos, Felix M., Univ. of Rochester, Rochester, New York, United States
  • Flotteron, Courtney A, Univ. of Rochester, Rochester, New York, United States
  • Chen, Luojing, Univ. of Rochester, Rochester, New York, United States
  • Bushinsky, David A., Univ. of Rochester, Rochester, New York, United States
Background

To study human idiopathic hypercalciuria (IH) we developed an animal model, genetic hypercalciuric stone-forming (GHS) rats, whose pathophysiology parallels that found in human IH. All GHS rats form calcium phosphate (CaP) kidney stones while there is no stone formation in the founder Sprague-Dawley (SD) rats. Previously, in GHS rats, we have shown that potassium citrate (KCit) increases urine supersaturation (ss) with respect to CaP but does not alter stone formation. In this study we tested the hypothesis that chlorthalidone (CTD) and KCit combined would reduce CaP stone formation in the GHS rats.

Methods

111th generation GHS rats were fed a fixed amount of a normal Ca (1.2%) and P (0.65%) diet, housed in metabolic cages and divided into four groups. Diets were supplemented with KCit (4 mmol/d) or CTD (4-5mg/kg/d), alone, or combined. Rats not receiving KCit were given KCl (4 mmol/d). Urine (u) was collected at 6, 12, and 18 wks for electrolyte analyses and kidney stone formation was determined by X-ray at 18 weeks.

Results

Compared to KCl, KCit reduced uCa (KCl=17.2±0.6 mg/d, KCit=14.9±0.3), CTD reduced it further (CTD= 12.4±0.5) and KCit+CTD reduced it even further (KCit+CTD=10.5±0.4). CTD raised uCit (KCl=112.1±3.6 mg/d, CTD=133.9±2.5) KCit raised it further (KCit=182.2±2.5) while KCit+CTD did not increase it further (KCit+CTD=171.7±3.2). KCit alone increased uP (KCl=20.4±0.6 mg/d, KCit=26.7±1.0). CTD did not change uCaP ss (KCl= 4.1±0.2 vs CTD=3.2±0.3), while KCit alone, or in combination with CTD, increased it (KCit=8.0±0.5, KCit+CTD=9.5±0.8). Compared to KCl (stone formation range of 0-4: KCl=2.6±0.3), KCit did not alter stone formation (3.3±0.3), while there was no stone formation in the GHS rats fed with CTD alone (CTD=0). The combination of KCit+CTD (2.0±0.3) resulted in more stones than CTD alone. All changes were significant to p<0.05.

Conclusion

Thus in GHS rats, who universally spontaneously form CaP stones, CTD alone is superior to KCit alone or in combination with CTD, in reducing stone formation.

Funding

  • NIDDK Support