Pathobiology and Diagnostics and Therapeutics of Hypocitraturia

Urinary citrate has dual functions as a urinary alkali and to chelate calcium as a soluble calcium-citrate complex to prevent precipitation as oxalate and phosphate salts. There are several related projects in our group centered on mechanisms of hypocitraturia. In addition to the known causes of hypocitraturia- acid loading and potassium deficiency, there are instances where urine citrate is labeled “idiopathic”. These are likely due to subtle defects in urinary acidification causing intracellular acidosis. We try to elucidate the mechanism of this condition. In addition to hypocitraturia, one important pathogenic factor for calcium phosphate stone is alkalinuria. Our laboratory is working out ways to increase urine citrate without raising urine pH to devise a therapy of calcium phosphate stones. Finally, in CKD, low serum bicarbonate is a relatively insensitive parameter for acid loading. Serum bicarbonate is the defended parameter whereas hypocitraturia is the defense mechanism, which is a much more sensitive read-out for acid-base disturbances. We are working out conditions where urine citrate can be used as a biomarker of acid-base disturbance in human CKD.