Introduction Most species in the animal kingdom employ an apatitebased endo or exoskeleton, which mandates an obligatory turnover of calcium and phosphorus in the organism. If all the minerals from skeletal turnover could be completely captured and re-utilized, one would have little need to ingest or excrete calcium and phosphorus. Recycling is, however, seldom complete in biology. For example, not all the iron from heme breakdown can be reused for hematopoiesis. There is a minimal mandatory amount of iron loss and hence iron ingestion is obligatory to sustain erythropoiesis and life. While we can render our urine virtually sodium free, there is a minimal obligatory amount of urinary calcium and phosphorus excretion, the latter exclusively in the form of inorganic phosphate. Even though external balance is achieved by calcium and phosphorus ingestion, this turnover imposes a formidable challenge to the excretory organ in terrestrial existence because the calcium and phosphate ion pair, which can associate in a large variety of chemical forms (eg CaHPO4, Ca3 (PO4) 2, Ca10 (PO4) 6 (OH) 2, Ca4O (PO4) 2) must be accommodated with a wide range of, but all relatively low, solubility product constants (eg CaHPO4: 1Â10À7 M; Ca3 (PO4) 2: 2.07 Â 10À33 M). This feat has to be accomplished in the lowest possible urine volume for the sake of water conservation on land. How do terrestrial species with apatite-based skeletons and obligatory low urine volumes keep urinary calcium and phosphate in solution? Numerous countermeasures are required to accommodate these two conflicting constraints. Two such strategies are directed at each of the two skeletal ions and are accomplished by the following (Fig. 1):(1) sequestering ionized calcium into a complex (with citrate) that has a high affinity constant and high solubility–both features that favor keeping calcium away from phosphate;(2) sequestering phosphate in the monovalent (H2PO4 À) and neutral (H3PO4) form and much less so in the calcium-binding divalent (HPO4 2À) form by maintaining a lower urinary pH.

In turns out that both of these ‘hijack tactics’ employ at least one common agent–citrate. Thus in basic and clinical physiology, one should view urinary citrate as an organic anion commissioned with two major roles: a major base equivalent and a principal chelator of urinary calcium.