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Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria - PubMed Skip to main page content
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. 2015 Dec;26(12):3001-8.
doi: 10.1681/ASN.2014121223. Epub 2015 Apr 8.

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

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

Nancy S Krieger et al. J Am Soc Nephrol. 2015 Dec.

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.

Keywords: hypercalciuria; kidney stones; mineral metabolism.

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Figures

Figure 1.
Figure 1.
Urinary calcium (Ca) was decreased and urinary, phosphate (P), and oxalate (Ox) were increased with K-cit. Urine was collected for 24 hours at 6, 12, and 18 weeks to determine solute levels as described in the Concise Methods. Values are mean±SEM. *K-cit different from KCl, same time period, P<0.05.
Figure 2.
Figure 2.
Urinary supersaturation (SS) of CaP and CaOx were increased and uric acid SS was decreased with K-cit. Urine was collected for 24 hours at 6, 12, and 18 weeks to determine solute levels that were used to calculate relative supersaturation as described in the Concise Methods. Values for relative supersaturation are mean±SEM and are unitless. *K-cit different from KCl, same time period, P<0.05.
Figure 3.
Figure 3.
K-cit decreased serum phosphate levels but did not change serum Ca or PTH. At the conclusion of the 18-week study, these levels were determined as described in the Concise Methods. Values are mean±SEM. *K-cit different from KCl, same time period, P<0.05.
Figure 4.
Figure 4.
Kidney stone formation and calcification was not different in rats fed KCl or K-cit. At the conclusion of the 18-week study, the extent of kidney stones and calcification was determined by three observers as described in the Concise Methods. Extent of kidney calcification was also determined as described in the Concise Methods. (A) Representative radiographs of kidneys from rats receiving KCl or K-cit. Calcification scores for the images shown are provided as a reference. (B) Quantitation of stone formation and calcification in all rats receiving KCl or K-cit. Values are mean±SEM.
Figure 5.
Figure 5.
Analysis of kidney stone crystals demonstrated CaP stones with both KCl and K-cit. Upper panels: Representative electron diffraction pattern of a stone from a rat fed KCl (left) and a stone from a rat fed K-cit (right) showing the typical configuration of biologic apatite. Lower panels: TEM images from the same stones used for the diffraction patterns: a stone from a rat fed KCl (left) and a stone from a rat fed K-cit (right).

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