Department of Nephrology, Second University of Naples, Naples, Italy.
J Nephrol. 2010 Nov-Dec;23 Suppl 16:S49-56.
Hypocitraturia is a known risk factor for kidney stone formation. By forming soluble complexes with calcium, citrate prevents crystal nucleation, aggregation and growth; therefore, the presence of citrate in the urine reduces the risk for calcium stone formation. Ingested citrate is rapidly metabolized, and plasma citrate levels vary little, so changes in filtered load do not significantly influence urinary citrate excretion. Changes in urinary citrate excretion are predominantly influenced by the rate of citrate absorption from the glomerular filtrate and metabolism by the proximal tubule cell. The former is mediated by the apical membrane cotransporter NaDC1, and the latter is mediated by both cytoplasmic and mitochondrial metabolism. Acid-base status is the most important physiological determinant of urinary citrate excretion, by modulating the activities of NaDC1 and cytoplasmic (ATP citrate lyase) and mitochondrial (m-aconitase) enzymes involved in citrate metabolism. Following an acid load, both the transport and metabolic processes are up-regulated leading to hypocitraturia; in contrast, an alkaline load increases citrate excretion, by regulating only the mitochondrial metabolic process.
低柠檬酸尿症是肾结石形成的已知风险因素。柠檬酸通过与钙形成可溶性复合物，防止晶体成核、聚集和生长；因此，尿液中柠檬酸的存在降低了钙结石形成的风险。摄入的柠檬酸被迅速代谢，血浆柠檬酸水平变化很小，因此滤过负荷的变化对尿柠檬酸排泄的影响不大。尿柠檬酸排泄的变化主要受肾小球滤过液中柠檬酸的吸收速率和近端肾小管细胞代谢的影响。前者由顶端膜协同转运蛋白 NaDC1 介导，后者由细胞质和线粒体代谢共同介导。酸碱状态是调节尿柠檬酸排泄的最重要的生理决定因素，通过调节柠檬酸代谢涉及的 NaDC1 和细胞质（三磷酸腺苷柠檬酸裂解酶）和线粒体（m-顺乌头酸酶）酶的活性。在酸负荷后，运输和代谢过程都被上调导致低柠檬酸尿症；相反，碱负荷仅通过调节线粒体代谢过程增加柠檬酸排泄。
