Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats

Abstract

To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.