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

• Published in: Journal of the American Society of Nephrology Vol. 26; no. 12; pp. 3001 - 3008
• Main Authors: Krieger, Nancy S, Asplin, John R, Frick, Kevin K, Granja, Ignacio, Culbertson, Christopher D, Ng, Adeline, Grynpas, Marc D, Bushinsky, David A
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01-12-2015
• Subjects: Animals; Basic Research; Calcium - urine; Calcium Oxalate - urine; Calcium Phosphates - analysis; Calcium Phosphates - urine; Calcium, Dietary - administration & dosage; Citric Acid - urine; Disease Models, Animal; Diuretics - therapeutic use; Hydrogen-Ion Concentration; Hypercalciuria - urine; Kidney Calculi - chemistry; Kidney Calculi - prevention & control; Kidney Calculi - urine; Male; Potassium Chloride - therapeutic use; Potassium Citrate - therapeutic use; Rats; Uric Acid - urine; Urine - chemistry; kidney stones; hypercalciuria; mineral metabolism
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2014121223

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.