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Abstract: TH-PO562

Chlorthalidone Plus Potassium Citrate Decreases Calcium Oxalate Stone Formation Better Than Either Agent Alone While Also Improving Bone Quality in Genetic Hypercalciuric Stone-Forming Rats

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Krieger, Nancy S., University of Rochester Medical Center, Rochester, New York, United States
  • Grynpas, Marc, Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada
  • Spataru, Daiana, Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada
  • Asplin, John R., Litholink Corporation, Chicago, Illinois, United States
  • Granja, Ignacio, Litholink Corporation, Chicago, Illinois, United States
  • Chen, Luojing, University of Rochester Medical Center, Rochester, New York, United States
  • Bushinsky, David A., University 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 found in human IH. All GHS rats spontaneously form calcium oxalate stones when the oxalate precursor, hydroxyproline is added to the diet. Here we tested the hypothesis that CTD and KCit combined would effectively reduce CaOx stone formation and improve bone quality in the GHS rats better than either agent alone.

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 a 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 and bone parameters were determined 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. There were no significant differences in CaOx supersaturation in any group. 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 the GHS rats fed with CTD alone (CTD=1.6±0.2). The combination of KCit+CTD (0.8±0.2) resulted in significantly fewer stones than CTD or KCit alone. Vertebral trabecular bone was increased by both CTD (38.5±3.2% vs CTL=26.8±5.1%) and KCit+CTD (34.7±3.4%), p<0.05 for both. Cortical bone area was increased by CTD (7.3±0.3 mm2 vs CTL=6.9±0.2 mm2) but not altered with KCit+CTD or with KCit alone. Mechanical properties of trabecular bone were improved by CTD alone, but not the combination.

Conclusion

Thus in GHS rats, when fed a diet that results solely in CaOx stone formation, the combination of KCit+CTD prevented stone formation better than either agent alone. The improvements in bone quality were principally due to CTD alone; adding KCit provides no additional benefit.

Funding

  • NIDDK Support