Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria

Abstract

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.

Low Sodium Diet Decreases Stone Formation in Genetic Hypercalciuric Stone-Forming Rats

“…However, in spite of an eight- fold reduction in dietary Na intake and a fall in uNa of 2.09 mmol, uCa fell by only 0.05 mmol. A similar decrease in uCa excretion was found in a previous study examining the effect of potassium citrate in GHS rats [44], while thiazides caused an even greater decrease in uCa [41] as well as improved BMD (20) compared to our findings in the current study [31]. The low Na diet also induced a reduction of uP, uCl, and uK but no differences in urine oxalate, citrate, ammonium, magnesium, pH, or volume.…”

“…4a) and an overall stone formation score determined as we have done previously [44]. Radiographic analysis of kidneys demonstrated a significant decrease in stone formation in …”

“…All of these methods have been used previously [31,36,[42][43][44]. Urine SS With the measured solute excretion, the urinary SS with respect to CaOx, CaP, and UA solid phases were calculated using the computer program EQUIL2 [45] as we have done previously [37,39,44,46,47]. Ratios of 1 denote a urine at equilibrium, those > 1 denote SS and those < 1 denote undersaturation.…”

Diethyl citrate and sodium citrate reduce the cytotoxic effects of nanosized hydroxyapatite crystals on mouse vascular smooth muscle cells

“…Citrate can bind intestinal and urine calcium and increase urine pH, metabolize to bicarbonate, and decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. 45,46 However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. 45 Thus, the effect of oral citrate on urine calcium oxalate, calcium phosphate supersaturation, and VC is complex and difficult to predict.…”

“…45,46 However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. 45 Thus, the effect of oral citrate on urine calcium oxalate, calcium phosphate supersaturation, and VC is complex and difficult to predict. Moreover, calcification in vitro and in patients with CKD substantially varies.…”