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Abstract: FR-PO527

The Combination of Chlorthalidone and Potassium Citrate Is More Effective Than Either Agent Alone in Decreasing Calcium Oxalate Stone Formation in Genetic Hypercalciuric Stone-Forming Rats

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Krieger, Nancy S., Univ. of Rochester Medical Center, Rochester, New York, United States
  • Asplin, John R., Litholink Corp, Chicago, Illinois, United States
  • Granja, Ignacio, Litholink Corp, Chicago, Illinois, United States
  • Multala, Evan, Univ. of Rochester Medical Center, Rochester, New York, United States
  • Flotteron, Courtney A., Univ. of Rochester Medical Center, Rochester, New York, United States
  • Chen, Luojing, Univ. of Rochester Medical Center, Rochester, New York, United States
  • Bushinsky, David A., Univ. of Rochester Medical Center, 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 of human IH. All GHS rats spontaneously form calcium phosphate (CaP) stones while there is no stone formation in the founder rats. When the oxalate precursor, hydroxyproline, is added to the diet, only calcium oxalate (CaOx) stones form. Previously, we demonstrated that chlorthalidone (CTD) alone was superior to potassium citrate (KCit) alone or in combination with CTD, in reducing CaP stone formation. In the current study we tested the hypothesis that CTD and KCit combined would effectively reduce CaOx stone formation in GHS rats.

Methods

113th generation GHS rats were fed a fixed amount of a normal Ca (1.2%) and P (0.65%) diet with 5% hydroxyproline added, housed in metabolic cages and divided into four groups. Diets were supplemented with KCl (4 mmol/d) as control, KCit (4 mmol/d), CTD (4-5mg/kg/d)+KCl, or KCit+CTD. Urine (u) was collected at 6,12, and 18 wks for analyses and kidney stone formation was determined by X-ray at 18 weeks.

Results

Compared to the KCl control, KCit reduced uCa (KCl= 17.2±0.3 mg/d, KCit=14.4±0.3), CTD reduced it further (CTD=13.0±0.6) and KCit+CTD reduced it even further (KCit+CTD=9.3±0.4). The combination of KCit+CTD decreased uOx compared to all other groups (KCl=3.4±0.2 mg/d, K Cit=3.5±0.2, CTD=3.5±0.1, KCit+CTD= 2.7±0.1). Compared to KCl (108.7±2.2 mg/d), KCit and CTD+KCit increased uCit (KCit=146.6±2.6, KCit+CTD=129.9±3.3). There were no significant differences in CaOx supersaturation (ss) in any group. CTD did not change uCaP ss (KCl= 4.3±0.3, CTD=2.3±0.2), while KCit alone, or in combination with CTD, increased it (KCit=10.3±0.6, KCit+CTD=11.5±0.9). Compared to KCl (stone formation with a range of 0-4: KCl=2.1±0.1), KCit did not alter stone formation (2.0±0.3), while there was less stone formation in rats fed CTD alone (CTD=1.6±0.2). The combination of KCit+CTD (0.8±0.2) resulted in significantly fewer stones than KCl, CTD or KCit alone.

Conclusion

Thus in GHS rats fed a diet that results solely in CaOx stone formation, the combination of KCit+CTD prevented stone formation better than either agent alone.

Funding

  • NIDDK Support