title: Low urinary citrate: an overview.
abstract: 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.
authors.affiliation: Department of Nephrology, Second University of Naples, Naples, Italy. miriamzacchia@virgilio.it
authors.forename: Miriam
authors.initials: M
authors.lastname: Zacchia
authors.forename: Patricia
authors.initials: P
authors.lastname: Preisig
mesh_terms: D000818:Animals; D019343:Citric Acid / Q000378:metabolism* / Q000652:urine; D029382:Dicarboxylic Acid Transporters / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000502:physiology; D027981:Symporters / Q000502:physiology
chemical_list: D029382:Dicarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; D027981:Symporters; D019343:Citric Acid