Urine pH and Citrate as Predictors of Calcium Phosphate Stone Formation.

Abstract

Urinary parameters including urine pH and citrate are recognized as critical in the pathophysiology of calcium-based stones. The factors contributing to variation in these parameters between calcium oxalate and calcium phosphate stone formers are however not well understood. In this study using readily available laboratory data, we explore these differences to delineate the odds of forming calcium phosphate (CaP) versus calcium oxalate (CaOx) stones. In this single-center retrospective study, we compared serum and urinary parameters between adult CaP stone formers (SF), CaOx SF, and non-stone formers (NSF). Urine pH was higher and urine citrate lower in CaP SF compared to same-sex CaOx SF and NSF. In CaP SF, higher urine pH and lower citrate were independent of markers of dietary acid intake and gastrointestinal alkali absorption, suggesting abnormal renal citrate handling and urinary alkali excretion. In a multivariable model, urine pH and urine citrate were most discriminatory between CaP SF and CaOx SF (Receiver Operating Characteristic Area Under the Curve of 0.73 and 0.65 respectively). An increase in urine pH by 0.35, a decrease in urine citrate by 220 mg/day, a doubling of urine calcium, and female sex all independently doubled the risk of CaP compared to CaOx. High urine pH and hypocitraturia are two clinical parameters that distinguish the urine phenotype of CaP SF from CaOx SF. The alkalinuria is due to intrinsic differences in the kidney independent of intestinal alkali absorption and is accentuated in the female sex.